The Skinny on Urine Production and Problems with It
Urine production begins when plasma leaves the glomerulus and enters Bowman’s space. Throughout the nephron and the collecting duct, materials are removed from the filtrate (reabsorption) or added to the filtrate via the tubule cells themselves (secretion) in order to conserve essential materials and eliminate those in excess, and to balance blood levels and remove toxins.
Urine Production
Urine production occurs as the result of the filtration process blood plasma goes through in the urinary system. A number of special vessels are required for this process to function.
What is glomerular filtrate?
Glomerular filtrate is often termed ultrafiltrate since it is not exactly the same as the plasma found in the blood. In fact, plasma passes through three filtration mechanisms before it is able to enter into Bowman’s space.
Glomerular Capillaries
Glomerular capillaries are a fenestrated type of capillary. This means that rather than materials diffusing first into the cell then diffusing out the other side, materials may pass through the pore in the endothelial cell for easier exiting of the blood stream. These pores are approximately 70–90 nm (nanometers) in diameter. Plasma is able to freely flow through these fenestrae with only the formed elements such as RBCs, WBCs, and platelets being retained in the blood vessels.
Basal Lamina
Underlying every epithelial cell is a molecular-rich layer called the basal lamina. The basal lamina is divided into two regions. Adjacent to the basal membrane of the cell is a less dense portion termed the lamina rara. An abundance of adhesive glycoproteins such as laminin and fibronectin provide anchorage points for the cells to attach to this extracellular foundation. Also found in the lamina rara are heparan sulfate proteoglycans. These consist of long linear protein cores. Polymers of disaccharides called glycosaminoglycans attach to these cores. This complexity is essentially geared to localize a high concentration of sulfate groups (negatively charged) in this layer to trap positively charged material from the plasma as it is becoming filtrate. Therefore, the lamina rara presents an ionic filtration step in filtrate formation. Also, since this layer is adjacent to the glomerulus, it is more specifically termed the lamina rara interna.
Below this layer is the much thicker and darker lamina densa. The greater density of this layer compared to the rara is due to the presence of type IV collagen, which is arranged into a meshwork much like a fishing net. Woven together, the spaces between opposing collagen molecules restrict passage of materials to anything smaller than 69 kDa (kilodaltons) and form a size-filtration step. The third layer, another lamina rara, is below the lamina densa, but is adjacent to the outer epithelial layer. This is called the lamina rara externa. It is composed of the same components as the lamina rara interna.
What is a kilodalton?
A kilodalton is 1,000 daltons. A dalton is a measurement on an atomic or molecular (that is, very tiny) scale. One hydrogen atom has a mass of 1 dalton.
Visceral Layer of Bowman’s Capsule
The cells of this layer are tightly adhered to every loop of the glomerular capillaries and create a functional barrier (filter) for the filtrate to pass through. The modified epithelial cells that compose this layer are called podocytes (pod meaning “foot”) because they have extensive and intricate cellular processes that completely cover the capillary loops. Podocytes interlock similarly to putting your hands together and interlocking your fingers to cup your hands to drink water. In doing so, spaces still exist between the fingers from which water can leak. These filtration slits create a portion of the third filtration step in the renal corpuscle. Between these slits, a membrane extends to further regulate the passage of materials into Bowman’s space.
Countercurrent Multiplier
In the intermediate loop, a continuous cycle of salt reabsorption followed by the osmosis of water out of the filtrate is created in the medulla of the kidney. Water is reabsorbed at the level of the descending limb, primarily due to the active pumping of Na (and the passive diffusion of Cl-) that happens in the ascending limb.
Sodium-potassium pumps actively transport Na+ into the interstitium (tissue surrounding the loop) and K+ is pumped (secreted) into the filtrate to offset the loss of Na+. Chloride follows the electrostatic attraction of Na+ and diffuses into the medullary interstitium to combine with Na+. It is important to note that the ascending limb is not permeable to water, so the filtrate becomes less concentrated with salt, which makes it hypotonic.
Because the NaCl from the ascending loop is accumulating in the interstitium, the deeper levels of the medulla, as well as the filtrate in the descending limb, become more hypertonic (1200–1400 mOsm: an mOsm being a milliosmole, or 1/100th of an osmole, a unit of measurement of osmotic pressure). There are no additional Na+/K+ pumps in this region of the loop; however, the descending limb is permeable to water, allowing water to be reabsorbed into the interstitium. This causes the filtrate to become more and more hypertonic (1400 mOsm at the bottom of the loop).
As salt and water are reabsorbed into the medulla of the kidney, the vasa recta and peritubular capillaries are responsible for removing the excess salt and water and returning it to the blood stream. If this material were not removed, the kidneys would reach too high a level of salt concentration and be unable to increase further, which would shut them down. Therefore it is as essential to remove the salt and water from the kidney as it is to remove these materials from the filtrate so that the cycle can continue.
Collecting Ducts
Due to the active (and passive) movements of solutes into the medullary interstitium and the removal of water by the vasa recta, the filtrate in the collecting duct is more dilute than even plasma (i.e., hypotonic). Remember that the collecting ducts run through the medulla on their way to the calyces and will encounter the same hypertonic, salt-rich environment, which drew water from the intermediate loop.
At this point, the final 27 L of the original filtrate is under hormonal control, primarily from antidiuretic hormone (ADH). Water is able to leave the collecting duct through aquaporins (protein channels that specifically allow the passive movement of water) in the plasma membrane of the collecting duct cells (principal cells). ADH leads to increased numbers of aquaporins in the membranes, and therefore greater reabsorption of water. However, even during dehydration, ADH cannot lead to more highly concentrated urine (above that of the interstitial fluid).
What is the minimum amount of urine produced per day?
The kidneys produce a minimum of 400 ml of urine per day even in the face of severe dehydration. This is called the obligatory water loss. This volume is required to remove the wastes from the blood.
Macula Densa
As the ascending loop returns from the medulla to the cortex, it transitions into the DCT and passes immediately by the vascular pole (entry and exit point of the glomerular arterioles) of its own renal corpuscle. In this region, next to the glomerulus, cells of the DCT are compressed together into the macula densa (literally translated “dark spot”). These specialized cells monitor the concentration of sodium and chloride and in doing so indirectly monitor blood pressure. For example, decreased blood pressure results in a decreased concentration of sodium and chloride ions at the macula densa. This is due to reduced filtration by the glomerulus. In response, the macula densa cells release prostaglandins, which trigger granular juxtaglomerular (JG) cells lining the afferent arterioles to release the enzyme renin into the blood stream, which in turn stimulates the production of chemicals that create thirst and cause blood vessels to constrict, increasing blood pressure. This process of regulating blood pressure and water balance is called the renin-angiotensin-aldosterone system (RAAS).
Along with the macula densa, the juxtaglomerular (JG or granular) cells contribute to what is called the juxtaglomerular apparatus.
Electrolyte Balance
As with the homeostatic balance of any system in the human body, changes in one area or the concentration of one element may have drastic effects on another. Therefore, as sodium and chloride are reabsorbed (to conserve water) and potassium is secreted to offset the conservation of sodium, an imbalance in electrolytes can easily and quickly occur if not regulated closely.
Acid-Base Balance
Since H+ can be secreted into the urine, the kidneys play an important role in the maintenance of proper blood, and therefore body, pH. H+ ions are filtered through the glomeruli and may be secreted into the filtrate via an antiport mechanism with Na+ in the DCT. This could explain the slightly acidic nature of urine.
Diseases and Disorders
Any condition that reduces the efficacy of the urinary system can have drastic effects on blood pressure (due to unregulated blood volume) and body toxicity (due to retention of wastes), and may eventually lead to kidney failure and death.
Kidney Stones
If the kidneys concentrate the urine excessively, then some minerals become supersaturated and yield a greater chance that through a nucleation event, they begin to form a crystal. As a seed crystal forms, the minerals accumulate on the crystal and increase in diameter. These kidney stones, also called renal calculi, can be passed in the urine if the crystal is less than 3 mm in size (the average diameter of the ureter). In this case, the individual may not even notice the stone. However, larger stones, which have jagged edges, can become lodged in the ureter until the building pressure of the urine forces the stone down the ureter. This causes considerable pain as well as damage. Often blood from the ureter appears in the urine (hematuria). If a stone becomes too large to pass safely, sound waves can be used to bombard the stone and shatter it into small enough pieces to pass through the urinary tract. This technique is termed lithotripsy (litho is derived from the Greek word meaning “stone”). Other techniques to fragment the stone into smaller pieces include laser catheterization to focus the laser beam directly on the stone.
Nephritis
Nephritis is inflammation of the kidneys. This is often caused by an infection. Other causes may include increased exposure of the kidneys to toxic agents or an autoimmune reaction that reduces kidney function. Typically, the patient exhibits reduced urine production, possibly blood in the urine (due to damaged renal corpuscles), and increasing levels of nitrogenous wastes accumulating in the blood (uremia). While infections of the body are not uncommon and most are not thought to be life threatening, nephritis is a serious disease and is one of the eight leading causes of human death worldwide.
Urinary Tract Infection
Any infection of the urinary tract may be termed urinary tract infection (UTI). Infections in the upper urinary tract are much more serious than those of the lower tract. Most commonly caused by the bacteria of the alimentary canal (E. coli), the infection begins in the urethra and, as the bacteria proliferates, extends upward in the urinary tract. Symptoms of a UTI include but are not limited to:
· painful urination (dysuria)
· cloudy urine due to the excessive number of bacteria populating the urine
· an increase in the sensation of urgency
· an increase in frequency of urination
Antibiotics and increased fluid intake (to cause increase urine production to flush the bacteria from the urinary tract) are the most common modes of treatment for a lower UTI.