Water Balance and Micturition

Hi :) In this post we'll take a look at an overview of water balance and the factors affecting changes in osmolarity and water movement in the body. We'll also discuss normo-, hypo- and hypervolaemia as well as how water is reabsorbed in various regions of the nephron. I'll explain how the medullary osmotic gradient is generated and maintained and why this gradient is important. I'll also discuss how ADH regulates water reabsorption in the nephron as well as the micturition reflex.

Water Balance

The amount of water in the body is balanced when the input of water equals the output. A positive water balance occurs when input exceeds output and a negative water balance occurs when output exceeds input. Water input largely comes from ingestion while a small amount is a result of cellular metabolism. Output is due to mainly excretion and other losses (such as sweating, from the breath etc).

Normovolaemia = a normal blood volume

Hypervolaemia = an increased blood volume

Hypovolaemia = a decreased blood volume

Water Reabsorption

 The kidneys are able to adjust the rate at which water is excreted to compensate for the changes in plasma volume and osmolarity. Seventy percent of water is reabsorbed at the proximal convoluted tubule where water reabsorption is unregulated, that is no hormones are involved. Here water follows the movements of solutes especially Na+. The distal tubule and collecting ducts of the nephron also reabsorb water, however, here the water excretion is regulated by Antidiuretic Hormone (ADH) which allows the kidneys to vary the volume of water excreted by the nephron. This is the place where concentration is fine-tuned.

To enable water balance, the kidneys regulate the osmolarity of the urine that they produce. Now, the normal osmolarity of blood plasma is 300mOsm. To get rid of excess water the kidneys excrete large volumes of dilute urine which has an osmolarity of 50mOsm. To conserve water, the kidneys concentrate the urine to approx. four times the osmolarity of plasma (~1400mOsm). The kidneys vary the urine volume and osmolarity by varying the water reabsorption at the distal nephron. The kidneys do this by creating and maintaining a medullary osmotic gradient. 

The Medullary Osmotic Gradient

The part of the medulla closest to the cortex has the lowest osmolarity (300mOsm) while the inner medulla has the highest osmolarity (1200-1400 mOsm). The distal nephron acts as a countercurrent multiplier. The fluid in the descending and ascending limbs of the loop of Henle (LOH) move in opposite directions. The descending limb of the LOH is permeable to water and no Na+, K+ or Cl- is transported there. The thick ascending limb of the LOH is impermeable to water and Na+, K+ and Cl- a transported by co-transporters.  The Medullary Osmotic Gradient is established in several steps:

1. Fluid enters the tubule and the active transport of Na+, Cl- and K+ ions occurs. This causes these ions to move into the medullary interstitial fluid which increases its osmolarity. 
2. This causes water to move out the descending limb of the LOH into the medullary interstitial fluid by osmosis.
3. The fluid in the descending limb reaches an iso-osmotic state. That is the osmolarity of the fluid in the descending limb is equal to that in the medullary interstitial fluid. There is an osmotic difference between the descending and ascending limbs.
4. More fluid enters the tubule and this pushes the existing fluid along the loop. More solutes are also pumped into the interstitial fluid. 
5. Water moves out the descending limb by osmosis.
6. The descending limb reaches an iso-osmotic state. An osmotic difference between the descending and ascending limbs exists. This cycle is repeated as the system is in a steady state. 

The osmolarity in the descending limb increases until 1400mOsm (in humans). The osmolarity of the ascending limb is always lower than the descending limb and decreases until it becomes hypo-osmotic. The osmotic gradient that is created does not dissipate because of the sluggish flow of blood through the vasa recta (the network of capillaries surrounding the distal nephron). This provides time for the osmotic gradient in the plamsa and interstitial fluid to equalise.

Because the fluid in the distal tubule and collecting duct is hypo-osmotic, water moves from the tubule to the interstitial fluid along an osmotic gradient, this is reabsorption. Water reabsorption requires a medullary osmotic gradient as well as permeability of the epithelium to water (this is dependent on ADH). The permeability of the epithelium to water is dependent on the presence of water channels in principal cells. Aquaporin-3 is always present in the basolateral membrane while Aquaporin-2 is present in the apical membranes when ADH is present in the blood.

Antidiuretic Hormone (ADH)

ADH (also known as vasopressin) is produced in the hypothalamus but is stored and secreted from the posterior pituitary gland. ADH is released into the blood in response to osmotic and baroreceptor signals. It acts on the cells of the distal nephron through several steps: 

1. ADH binds to basolateral receptor
2. Activates 2nd messenger
3. Increased synthesis and insertion of Aquaporin-2 channels into apical membrane
4. water permeability increased within 5-10 minutes. This causes the urine to be concentrated.
5. Aquaporin 3 is always present on the basolateral membrane. 

ADH secretion is stimulated by: increased ECF osmolarity, hypovolaemia, decreased mean arterial pressure, stress, nausea and vomiting, nicotine. ADH release is inhibited by: decreased exctracellular fluid osmolarity, hypervolaemia, increased mean arterial pressure and alcohol. 

In the absence of ADH, the late distal nephron becomes impermeable to water and water remains in the tubules despite the medullary osmotic gradient. This results in a large volume of dilute urine to be produced. In the presence of ADH the late distal nephron becomes permeable to water and it moves into the peritubular fluid because of the osmotic gradient. This causes small volumes of concentrated urine to be produced.

Species Differences in Urine Concentrating Ability

The ability to concentrate urine is dependent on the ratio of cortical to juxtamedullary nephrons. The more juxtamedullary nephrons present, the more concentrated the urine can be. Consequently, humans, which have 17% juxtamedullary nephrons, can generate a urine concentration of 1400mOsm. Dogs and cats, on the other hand, can produce concentrations of 2400mOsm and 3300mOsm respectively due to their ratio of 80% juxtamedullary nephrons. This is because the more juxtamedullary nephrons are present, the longer the tubules become. This allows a higher osmotic gradient to be generated which leads to more concentrated urine production.

The Micturition Reflex

This is the reflex which is involved in urination. The kidneys produce the urine while the bladder stores it. The bladder has several muscles which are under involuntary and voluntary control. The detrusor muscle, which is located in the wall of the bladder is under involuntary control. The internal urethral sphincter is also involuntarily controlled while the external urethral sphincter is under voluntary control. 

When the bladder fills with urine the bladder wall expands and this activates stretch receptors located in the wall. These stretch receptors communicate with the spinal cord and work to:

• Decrease the sympathetic activity: this causes the internal urethral sphincter to relax which causes it to open.
• Increase parasympathetic activity. This causes the detrusor muscle to contract and also causes the internal urethral sphincter to open.
• Decrease in somatic motor neuron activity. This causes the external urethral sphincter to relax and open. 

The opening of the internal and external urethral sphincters lead to micturition (urination). 

That's all for this post, see you next time :)