**2.1 Countercurrent mechanisms and modelling of urine concentration**

The concentration ability of the kidney is provided by a highly hyperosmotic renal medulla, which draws H2O from the urinary filtrate within the collecting duct. The mechanism for providing and maintaining this highly hyperosmotic environment is found to be due to several mechanisms. The countercurrent multiplier process in the loop of Henle provides one of the most important mechanisms for this purpose. If the renal tubule is straight, it can provide a osmotic gradient within the renal medulla by about 300 mOsm/L, through an active Na+ transport. However, for this gradient to continue, it requires rapid replacement against washout or dissipation of the osmotic environment in the renal medulla.

By looping the tubule in a parallel configuration and iterating the single effect of concentration, the kidney can generate and maintain the medullary concentration gradient up to 1200-1400 mOsm/L with lower energy costs. The two parallel tubes of the descending limb and the ascending limb of the loop of Henle are looped in close proximity in the hairpin configuration (figure 1). The production of a chemical osmotic gradient is based on the active sodium reabsorption (requiring ATP) from the ascending loop; the maintenance of this gradient is crucial. The osmolality of interstitium in almost all parts of the body is about 300 mOsm/L. However, in the renal interstitium, the countercurrent mechanism provides increases up to 4 times from 300 mOsm/L to almost 1400 mOsm/L.

The hyperosmotic gradient provides the osmotic pressure to draw passive diffusion of water from the descending limb and the collecting duct. The countercurrent parallel design allows the descending limb to feedback to the ascending limb, forming a closed stable system of hyperosmolar environment and gradient, as shown in figure 2. It is the preservation of this hyperosmolar environment in steady state conditions that allows the urinary filtrate to be concentrated rapidly and efficiently.

There is also a parallel system of renal vascular network of the vasa recta to prevent this hyperosmolar environment from dissipation. The contribution of the vasa recta into the concentrating mechanism is shown as follows: assume the interstitial tissue of cortex and glomerular filtrate are iso-osmotic to plasma. The tubular fluid entering the descending loop of Henle is also iso-osmotic to plasma. This fluid becomes progressively concentrated towards the bend. In the ascending loop it becomes less concentrated as it reaches the cortex. Under the influence of anti-diuretic hormone, blood flow through the vasa recta is

Structurally, there are 500,000 – 1,000,000 nephron units in the kidney [1,2]. Each nephron has a length of 40 mm and tubular diameter of 50 um. Microscopic puncture and perfusion techniques make it possible to measure single-nephron filtration rates, absorption and secretion rates. The single-nephron glomerular filtration rate (SNGFR) is approximately

Approximately 1200 ml/min of blood flow to the kidneys which represents 20% of total cardiac output. In the filtration mechanism, a total filtration surface of 1 m2 is found. A global renal fitrate of 120 ml/min (180 L/day) is produced by both kidneys, of which 99.4% of water is reabsorbed to yield about 1 liter of urine/day. The concentration ability of the renal system is largely resides in the tubular system embedded within the renal medulla.

In this paper we will analyse the operating characteristics of the renal system and examine the optimal features of several aspects of renal physiological engineering mechanisms, particularly, the countercurrent multiplier mechanism for urine concentration and how

The concentration ability of the kidney is provided by a highly hyperosmotic renal medulla, which draws H2O from the urinary filtrate within the collecting duct. The mechanism for providing and maintaining this highly hyperosmotic environment is found to be due to several mechanisms. The countercurrent multiplier process in the loop of Henle provides one of the most important mechanisms for this purpose. If the renal tubule is straight, it can provide a osmotic gradient within the renal medulla by about 300 mOsm/L, through an active Na+ transport. However, for this gradient to continue, it requires rapid replacement

By looping the tubule in a parallel configuration and iterating the single effect of concentration, the kidney can generate and maintain the medullary concentration gradient up to 1200-1400 mOsm/L with lower energy costs. The two parallel tubes of the descending limb and the ascending limb of the loop of Henle are looped in close proximity in the hairpin configuration (figure 1). The production of a chemical osmotic gradient is based on the active sodium reabsorption (requiring ATP) from the ascending loop; the maintenance of this gradient is crucial. The osmolality of interstitium in almost all parts of the body is about 300 mOsm/L. However, in the renal interstitium, the countercurrent mechanism provides

The hyperosmotic gradient provides the osmotic pressure to draw passive diffusion of water from the descending limb and the collecting duct. The countercurrent parallel design allows the descending limb to feedback to the ascending limb, forming a closed stable system of hyperosmolar environment and gradient, as shown in figure 2. It is the preservation of this hyperosmolar environment in steady state conditions that allows the

There is also a parallel system of renal vascular network of the vasa recta to prevent this hyperosmolar environment from dissipation. The contribution of the vasa recta into the concentrating mechanism is shown as follows: assume the interstitial tissue of cortex and glomerular filtrate are iso-osmotic to plasma. The tubular fluid entering the descending loop of Henle is also iso-osmotic to plasma. This fluid becomes progressively concentrated towards the bend. In the ascending loop it becomes less concentrated as it reaches the cortex. Under the influence of anti-diuretic hormone, blood flow through the vasa recta is

Figure 1 demonstrates the disparate functionality of the renal nephron unit.

**2.1 Countercurrent mechanisms and modelling of urine concentration** 

against washout or dissipation of the osmotic environment in the renal medulla.

increases up to 4 times from 300 mOsm/L to almost 1400 mOsm/L.

urinary filtrate to be concentrated rapidly and efficiently.

optimal renal function in terms of renal clearance is maintained.

**2. Kidney functional analysis** 

30 nl/min.

decreased and osmotic equilibration of blood in the vasa with medullary interstitium is enhanced. In brief, the anatomical configuration of the vasa recta minimises but does not prevent solute loss from the medulla via the blood.

Other mechanisms in concentration include the role of urea re-circulated from the collecting duct, the role of vasopressin (antidiuretic hormone or ADH) acting on water transport cellular membrane water channel proteins aquasporin 1, 2, 3 and 4 regulating water permeability. Mutations of several aquasporin genes lead to loss of function and marked abnormalities of water balance, as documented in several reports involving AQP1 knock-out animals.

The contribution of urea to the concentration gradient in the renal medulla is also an important consideration. Diffusion of H2O occurs from the tubular lumen into the interstitium. Active transport of Na+ occurs from the tubular fluid. The withdrawal of H2O from the collecting tubule leads to increased concentration of urea in the collecting tubule, causing a high gradient across the duct membrane, which favours diffusion of urea from the collecting duct into the medulla. From there, the urea diffuses into the descending loop of Henle and is re-circulated into the collecting duct. This contributes to the high urea content and osmolality of the medulla in the concentrating kidney.
