Renal Handling of Urea, Sodium and Potassium

Hello :) In this post we’ll take a look at how urea is handled by the body. I’ll describe the details of how the kidneys handle urea as well as why urea recycling is important. We’ll look at the differences between mammalian and avian excretion of nitrogenous wastes as well as how the kidney’s regulate sodium and potassium balance. In addition, we’ll discuss the key differences between aldosterone, ADH (antidiuretic hormone), and ANP. I’ll finish off by explaining why an increase in Na+ concentration does not increase K+ excretion. Don’t forget, if you have any questions about this post, please feel free to ask me in the comments section at the end of the page :)

The Handling of Urea

Urea is a nitrogenous end-product of protein catabolism and is excreted by the kidneys as waste. The breakdown of amino acids releases ammonia which is toxic to the body. Because of this, the ammonia is converted to urea which is less toxic. The concentration of urea in the blood is referred to as blood urea nitrogen (BUN). When elevated BUN and creatinine levels exist the situation is referred to as azotaemia. 

Handling of Urea at the Proximal Convoluted Tubule

About 50% of the urea which is filtered by the glomerulus is passively reabsorbed at the proximal convoluted tubule. Urea is reabsorbed at the PCT through several steps: 

1.  It is freely filtered at the glomerulus 
2.  Active reabsorption of the solutes then occurs, this increases the peritubular fluid and plasma osmolarity
3. Water is then reabsorbed because it follows the movement of the solutes into the plasma
4. This water reabsorption creates a urea concentration gradient. This is because the tubular fluid has a higher concentration of urea than the blood plasma.
5. Passive urea movement then occurs from the tubule to the blood plasma. This is completely dependent on water movement.

Handling of Urea at the Distal Nephron

The loop of Henle, distal convoluted tubule and the collecting duct in the outer medulla are impermeable to urea and water reabsorption increases the concentration of the urea in the tubular fluid. The permeability to urea increases at the collecting ducts of the inner medulla and facilitated diffusion of urea occurs here. This diffusion is enhanced by antidiuretic hormone. 

Ten per cent of the urea which is filtered by the glomerulus is reabsorbed into the plasma at the collecting duct in the inner medulla. This occurs because the urea passively diffuses into the medullary interstitial fluid and into the plasma. Some of this urea re-enters the thin ascending loop of Henle and is ‘recycled’. The reabsorption of urea in this way decreases during times of reduced water reabsorption and when ADH is absent.

Mammals vs. Birds

As described earlier in this post, mammals excrete urea in order to get rid of their nitrogen. Birds, on the other hand, excrete uric acid in order to get rid of nitrogen. Uric acid requires less water to make when compared to urea and is made mainly by the birds’ reptilian-like nephrons. Birds do not have bladders, instead they have a cloaca. In the cloaca, birds are able to adjust the water and salt content and regulate the osmolarity of their waste.  

Sodium Balance

Because sodium is the main solute in the extracellular fluid, it is important for its balance to be regulated so that normal osmolarity can be maintained. When sodium levels in the blood plasma are higher than normal, the condition is known as hypernatremia. When lower than normal it is known as hyponatremia. Sodium levels are regulated through absorption in the kidneys.

More than 99% of the Na+ which is filtered at the glomerulus is reabsorbed. 60-65% of this occurs unregulated at the proximal tubule; 25-30% occurs in the thick ascending limb of the loop of Henle; while 10% happens in the distal nephron under control of aldosterone.

Reabsorption at the Proximal Convoluted Tubule

Here, reabsorption is unregulated. It is driven by the Na+/K+ pump which actively transports sodium across the basolateral membrane into the blood plasma. This creates a low concentration of Na+ in the proximal tubule epithelial cell. This allows Na+ to move across the apical membrane into the epithelial cell from the tubular fluid using co-transport with other solutes and counter transport with H+.

Reabsorption of Sodium at the Distal Nephron

Reabsorption at the distal nephron occurs through Na+/K+ ATPase which creates a very low intracellular sodium concentration. Sodium then moves along its concentration gradient across the apical membrane through co-transport with other solutes (eg. Cl-) and through ion channels (which is coupled with K+ secretion).  Reabsorption here is regulated by aldosterone and atrial natriuretic peptide (ANP).

Aldosterone is a steroid hormone which is produced and released at the adrenal cortex and its release is stimulated by the presence of Angiotensin 2. Aldosterone regulates Na+ reabsorption and K+ secretion at the distal nephron and indirectly leads to increased water reabsorption through increased ECF osmolarity. 

Aldosterone binds to the receptors in the cytosol of the principal cells in the late distal convoluted tubule and collecting ducts. This binding stimulates the synthesis and opening of Na+ and K+ channels at the apical membrane. The synthesis and insertion of Na+/K+ pumps occurs at the basolateral membrane.  This has the effect of simultaneously increasing sodium reabsorption and potassium excretion.  

ANP is secreted from the atrial walls in response to distension associated with an increased blood volume. 

ANP inhibits sodium reabsorption. It also increases the filtration, and thus the secretion, of sodium by increasing the glomerular filtration rate by dilating the afferent and constricting the efferent arteriole. It decreases the reabsorption of sodium by limiting the number of open sodium channels on the apical surface of the principal cells. It also inhibits RAAS by decreasing the renin and aldosterone secretion.  

Potassium Balance

The ratio of intracellular to extracellular potassium concentrations is very important to the function of excitable cells. Small changes in the concentration of potassium can affect nerves as well as cardiac, skeletal and smooth muscle. Hyperkalaemia refers to a situation where the potassium concentrations in the blood are higher than normal. Hypokalaemia is when potassium levels in the plasma are lower than normal.

At the glomerulus, potassium ions are freely filtered from the blood and both secretion and absorption occur within the tubule. Unregulated active reabsorption occurs at in the proximal convoluted tubule (55%) and the loop of Henle (30%). Regulated secretion and reabsorption occurs in the late distal tubule and collecting duct and is dependent on the dietary intake of potassium. However, the regulation of potassium levels in the blood occurs through secretion at the distal nephron.

Reabsorption at the Proximal Tubule

Active Na/K+ pumps on the basolateral membrane of the tubule epithelial cell pump K+ from the peritubular fluid into the epithelial cell. An unknown mechanism also transfers K+ from the tubular fluid in to the epithelial cell. K+ then moves down its concentration gradient across the basolateral membrane into the peritubular fluid. K+ can also be reabsorbed through paracellular diffusion.  

The Handling of Potassium at the Distal Nephron

If the animal’s diet has high amounts of potassium, potassium will be excreted at the principal cells in the distal nephron. If the diet is low in potassium, reabsorption will occur at the intercalated cells. This is also where sodium reabsorption occurs.  

At the principal cells K+ moves from the peritubular fluid into the cell through the Na/K pump across the basolateral membrane. This is an active process. Potassium also moves down its concentration gradient through ion channels into the renal tubule across the apical membrane. This is a passive process.

Now, aldosterone increases the amount of Na/K on the basolateral membrane and the amount of K+ channels on the apical membrane. This aldosterone is regulated by the RAAS and the concentration of potassium. High potassium levels in the extracellular fluid stimulate the release of aldosterone.

At the intercalated cells, potassium is reabsorbed while H+ is secreted when there is a depletion in potassium. This occurs through an H+/K+ exchange at the apical membrane.

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