Everyday 180 L of glomerular filtrate is formed with large quantity of water. If this much of water is excreted in urine, body will face serious threats. So, the concentration of urine is very essential.

Osmolarity of glomerular filtrate is same as that of plasma and it is 300 mOsm/L. But normally urine is concentrated and its osmolarity is four times more than that of plasma, i.e., 1,200 mOsm/L.

Factors Determining Osmolarity of Urine

Osmolarity of urine depends upon two factors, water content in the body and antidiuretic hormone (ADH).

Mechanism of urine formation is the same for dilute urine and concentrated urine till the fluid reaches distal convoluted tubule. However, dilution or concentration of urine depends upon water content of the body.

When water content in the body increases, kidney excretes dilute urine. This is achieved by inhibition of ADH secretion from posterior pituitary.

Water reabsorption from renal tubules does not take place leading to excretion of large amount of water. Thus, the urine gets dilute.

When the water content in body decreases, kidney retains water and excretes concentrated urine.

Formation of concentrated urine involves two processes:

1. Development and maintenance of medullary gradient by countercurrent system.
2. Secretion of ADH.

Medullary Gradient

Medullary gradient refers to the gradual increase in osmolarity of medullary interstitial fluid. It plays an important role in the concentration of urine.

Medullary Hyperosmolarity

Interstitial fluid in renal cortex is isotonic to plasma with the osmolarity of 300 mOsm/L. Osmolarity of interstitial fluid in medulla near the cortex is also 300 mOsm/L.

However, while proceeding from outer part towards the inner part of medulla, osmolarity increases gradually and reaches the maximum at inner most part of medulla near renal sinus. Here, it is 1,200 mOsm/L.

Kidney has some unique anatomical arrangements called countercurrent system, which are responsible for the development and maintenance of medullary gradient and hyperosmolarity of interstitial fluid in the inner medulla.

Countercurrent System

A countercurrent system is a system of ‘U’ shaped tubules (tubes) in which flow of fluid is in opposite direction in two limbs of the U-shaped tubules.

In kidney, the direction of flow of fluid in the descending limb is just opposite to the direction of flow in the ascending limb.

Divisions of Countercurrent System in Kidney

1. Countercurrent multiplier formed by loop of Henle.
2. Countercurrent exchanger formed by vasa recta.

Countercurrent Multiplier

Loop of Henle

Loop of Henle functions as countercurrent multiplier. It is responsible for development of hyperosmolarity of medullary interstitial fluid and medullary gradient.

Role of Loop of Henle in Development of Medullary Gradient

Loop of Henle of juxtamedullary nephrons plays a major role as countercurrent multiplier. It is because the loop of Henle of juxtamedullary nephron is long and extends up to deeper parts of medulla.

Events During Development of Medullary Gradient by Countercurrent Multiplier

1. Hyperosmolarity of medullary interstitial fluid is due to active reabsorption of sodium chloride and other solutes from ascending limb of Henle’s loop into the medullary interstitium. These solutes accumulate in medullary interstitium and increase the osmolality.
2. Due to the concentration gradient, sodium and chloride ions diffuse from medullary interstitium into the descending limb of Henle’s loop. Then the fluid reaches ascending limb again.
3. Sodium and chlorine ions are repeatedly recirculated between descending limb and ascending limb of Henle’s loop through medullary interstitial fluid leaving a small portion to be excreted in urine.
4. Apart from this, there is regular addition of more and more new sodium and chlorine ions into descending limb by constant filtration.

Other Factors Responsible for Hyperosmolarity of Medullary Interstitial Fluid

1. Reabsorption of Sodium from Collecting Duct

Reabsorption of sodium from medullary part of collecting duct into medullary interstitium adds to the osmolarity of medullary interstitium.

2. Recirculation of Urea

Fifty percent of urea filtered in glomeruli is reabsorbed in proximal convoluted tubule. Almost an equal amount of urea is secreted in loop of Henle. So, the fluid in distal convoluted tubule has same amount of urea as filtered.

Due to concentration gradient, urea diffuses from collecting duct into the inner medullary interstitium. So, the osmolarity increases in the inner medulla.

Again, by concentration gradient, urea enters the ascending limb. From here, it passes through distal convoluted tubule and reaches the collecting duct. From here, urea enters medullary interstitium and the cycle is repeated.

By this way urea recirculates repeatedly, and helps to maintain hyperosmolarity in the inner medullary interstitium.

Only a small amount of urea is excreted in urine.

Urea recirculation accounts for 50% of hyperosmolarity in inner medulla.

Countercurrent Exchanger

Vas rectum functions as countercurrent exchanger. It is responsible for maintenance of hyperosmolarity of medullary interstitial fluid and the medullary gradient developed by countercurrent multiplier.

Role of Vas Rectum in Maintenance of Medullary Gradient

Vas rectum runs parallel to loop of Henle. Descending limb of each vas rectum runs along the ascending limb of Henle’s loop and its ascending limb runs along with descending limb of Henle’s loop.

Because of this type of position vas rectum acts like countercurrent exchanger.

Events During Maintenance of Medullary Gradient by Countercurrent Exchange

1. Sodium chloride is reabsorbed from ascending limb of Henle’s loop and enters the medullary interstitium. From here it enters the descending limb of vas rectum.
2. Simultaneously water diffuses from descending limb of vas rectum into medullary interstitium.
3. Blood flows very slowly through vas rectum. So, large quantity of sodium chloride accumulates in descending limb of vas rectum and flows slowly towards ascending limb.
4. By the time blood reaches ascending limb of vas rectum, concentration of sodium chloride increases very much.
5. This causes diffusion of sodium chloride into the medullary interstitium.
6. Simultaneously, water from medullary interstitium enters the ascending limb of vas rectum. The cycle is repeated.

If the vas rectum would be a straight vessel without hairpin arrangement, blood would leave the kidney quickly at renal papillary level. In that case, the blood would remove all the sodium chloride from interstitium and thereby hyperosmolarity would be decreased. However, this does not happen, since the vas rectum has a hairpin bend.

Therefore, when blood passes through the ascending limb of vas rectum, sodium chloride diffuses out of blood and enters the interstitial fluid of medulla and water diffuses into the blood.

Recirculation of Urea Through Vas Rectum

Recirculation of urea occurs through vas rectum also. From medullary interstitium, along with sodium chloride, urea also enters the descending limb of vas rectum.

When blood passes through ascending limb of vas rectum, urea diffuses back into the medullary interstitium along with sodium chloride.

Thus, sodium chloride and urea are exchanged for water between the ascending and descending limbs of vas rectum, hence this system is called countercurrent exchanger.

Final concentration of urine is achieved by antidiuretic hormone (ADH).

Normally, distal convoluted tubule and collecting duct are not permeable to water. In the presence of ADH, distal convoluted tubule and collecting duct become permeable to water resulting in water reabsorption.

Water reabsorption induced by ADH is called facultative reabsorption of water.

A large quantity of water is removed from the fluid passing through distal convoluted tubule and collecting duct. So, urine becomes hypertonic with an osmolarity of 1,200 mOsm/L.

When glomerular filtrate passes through renal tubules, its osmolarity is altered in different segments as described below.

1. Bowman’s Capsule

Glomerular filtrate collected at the Bowman’s capsule is isotonic to plasma. This is because it contains all the substances of plasma except proteins. Osmolarity of the filtrate at Bowman’s capsule is 300 mOsm/L.

2. Proximal Convoluted Tubule

When the filtrate flows through proximal convoluted tubule, there is active reabsorption of sodium and chloride followed by obligatory reabsorption of water.

So, osmolarity of fluid remains the same as in case of Bowman’s capsule, i.e., 300 mOsm/L. Thus, in proximal convoluted tubules, the fluid is isotonic to plasma.

3. Thick Descending Segment

When fluid passes from proximal convoluted tubule into thick descending segment, water is reabsorbed into outer medullary interstitium by means of osmosis. It is due to increased osmolarity in the medullary interstitium, i.e., outside the thick descending tubule.

Osmolarity of fluid inside this segment is between 450 and 600 mOsm/L. That means the fluid is slightly hypertonic to plasma.

4. Thin Descending Segment of Henle’s Loop

As the thin descending segment of Henle’s loop passes through inner medullary interstitium, which is increasingly hypertonic, more water is reabsorbed.

This segment is highly permeable to water, so the osmolarity of tubular fluid becomes equal to that of the surrounding medullary interstitium.

In the short loops of cortical nephrons, osmolarity of fluid at hairpin bend of loop becomes 600 mOsm/L.

In long loops of juxtamedullary nephrons, at the hairpin bend, osmolarity is 1,200 mOsm/L. Thus, in this segment the fluid is hypertonic to plasma.

5. Thin Ascending Segment of Henle’s Loop

When the thin ascending segment of Henle’s loop ascends upwards through medullary region, osmolarity decreases gradually.

Due to concentration gradient, sodium chloride diffuses out of tubular fluid and osmolarity decreases.

6. Thick Ascending Segment

This segment is impermeable to water. But there is active reabsorption of sodium and chloride from this segment.

Reabsorption of sodium decreases the osmolarity of tubular fluid to a greater extent. The osmolarity is between 150 mOsm/L and 200 mOsm/L. The fluid inside becomes hypotonic to plasma.

7. Distal Convoluted Tubule and Collecting Duct

While entering distal convoluted tubule, osmolarity of fluid is 200 mOsm/L and it is isotonic to plasma.

In the presence of ADH, distal convoluted tubule and collecting duct become permeable to water resulting in water reabsorption.

Reabsorption of large quantity of water increases the osmolarity to 1,200 mOsm/L. The urine becomes hypertonic to plasma.

Osmolarity of Fluid at Different Parts of Nephron

1. Diuresis

Diuresis is the excretion of large quantity of water through urine.

Diuresis is classified into two types:

1. Osmotic diuresis.
2. Water diuresis.

i. Osmotic Diuresis

Osmotic diuresis is the diuresis induced by presence of some osmotically active substances such as glucose in renal tubule.

Such substances increase osmotic pressure in renal tubules and reduce reabsorption of water resulting in excretion of water through urine.

Osmotic diuresis is common in diabetes mellitus because of high blood glucose level.

ii. Water Diuresis

Water diuresis is a type of diuresis due to decreased reabsorption of water in renal tubules particularly in distal convoluted tubule and collecting duct.

It is caused by deficiency of antidiuretic hormone.

Water diuresis is common in diabetes insipidus.

2. Polyuria

Polyuria is the increased urinary output with frequent voiding.

It is due to osmotic diuresis as in diabetes mellitus or water diuresis as in diabetes insipidus.

3. Syndrome of Inappropriate Hypersecretion of ADH (SIADH)

It is a pituitary disorder characterized by hypersecretion of ADH.

Excess ADH causes water retention, which decreases osmolarity of ECF.

4. Nephrogenic Diabetes Insipidus

Sometimes ADH secretion is normal, but renal tubules fail to give response to ADH resulting in polyuria.

This condition is called nephrogenic diabetes insipidus.

5. Bartter’s Syndrome

Bartter’s syndrome is a genetic disorder characterized by dysfunction of thick ascending segment and distal convoluted tubule resulting in loss of sodium, potassium, calcium and chloride through urine.

6. Oliguria and Anuria

Oliguria is a condition with decreased output of urine. Urine output is less than 400 mL per day in this condition.

It is different from another condition called anuria in which urine output is zero to 100 mL per day. Anuria means absence of urine output.

Common Causes of Oliguria

1. Acute renal failure.
2. Obstruction in urinary tract.
3. Infection or trauma of kidneys.
4. Heart failure.
5. Dehydration.
6. Medications such as certain antibiotics, chemotherapy and immunosuppressant drugs that may be toxic to kidneys.