Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, implying that dysfunctional secretion has serious clinical consequences. Tubular secretion measurement as an independent marker of kidney function may provide insight into the aetiology of kidney disease and improve the prediction of adverse outcomes. In a prospective cohort study of 298 patients with kidney disease, we estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulphate, and indoxyl sulphate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples. We calculated GFR using the mean clearance of creatinine and urea from the same samples and looked at the relationships between renal secretion and participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate was moderately correlated with eGFR and associated with some participant characteristics, most notably electrolyte fractional excretion.
Tubular Secretion
The peritubular capillary network removes hydrogen, creatinine, and drugs from the blood and deposits them in the collecting duct.
Tubular secretion is the process by which materials are transferred from peritubular capillaries to the renal tubular lumen; it is the inverse of reabsorption. Active transports and passive diffusions are the primary cause of the secretion.
Only a few substances are usually secreted, and they are usually waste products. Urine is the substance that remains in the collecting duct after reabsorption and secretion.
Mechanisms of Secretion
The mechanisms of secretion are similar to those of reabsorption, but these processes take place in the opposite direction.
Passive diffusion
The movement of molecules within the nephron from the peritubular capillaries to the interstitial fluid
Active transport
The movement of molecules through ATPase pumps that transport the substance through the renal epithelial cell into the nephron lumen
Renal secretion differs from reabsorption in that it filters and cleans substances from the blood instead of retaining them. The following substances are secreted into the tubular fluid for removal from the body:
- Ions of potassium (K+)
- Ions of hydrogen (H+)
- Ions of ammonium (NH4+)
- Creatinine
- Some hormones contain urea.
- Some medication (e.g., penicillin)
Many pharmaceutical drugs are protein-bound molecules that demonstrate the basic physiologic mechanisms of the kidney as well as the three steps involved in urine formation. Filtration, reabsorption, secretion, and excretion are easily secreted, which is why urine testing can detect drug exposure to a wide range of substances. Tubular secretion occurs throughout the nephron, from the proximal convoluted tubule to the collecting duct at the nephron’s end.
Hydrogen Ion Secretion
The tubular secretion of H+ and NH4+ from the blood into the tubular fluid regulates blood pH. The movement of these ions also aids in the conservation of sodium bicarbonate (NaHCO3). Urine typically has a pH of around 6, whereas blood should have a pH of 7 to 7.
Because of the exchange of carbon dioxide (a component of carbonic acid in the blood), pH regulation is primarily a respiratory system process; however, tubular secretion also contributes to pH homeostasis.
Following Secretion
Urine produced by the three processes of filtration, reabsorption, and secretion exits the kidney via the ureter and is stored in the bladder before exiting via the urethra. It is only about one percent of the original filtered volume at this point, consisting mostly of water with highly diluted amounts of urea, creatinine, and variable ion concentrations.
Location of Tubular Secretion
Tubular secretion occurs in humans and other vertebrates in the kidneys, where blood is filtered in specialised structures known as nephrons. These structures are made up of a long tubule surrounded by numerous capillaries. The secreted substances enter the tubule from the blood via peritubular capillaries and pass through the interstitial fluid before passing through the tubule wall (known as the transport epithelium) and into the tubule lumen (known as the lumen). Different aspects of secretion occur in the proximal and distal portions of each tubule, but not in the region known as the Henle loop.
Mechanism of Tubular Secretion
Many substances filtered in the kidney move between nephron regions via diffusion and osmotic gradients, but tubular secretion occurs via active transport. In the membrane of the tubular cells that make up the transport epithelium, there are several different types of transporter proteins. These transporters transport various substances into the tubular lumen, and they require energy in the form of ATP to function. Different types of transporters are found in different regions of the tubule, which influences their function.
The proximal tubule is where drugs and toxins are secreted. To maintain an ideal pH, H+ is transported in both the proximal and distal tubule regions. The Na+ – H+ exchanger is an example of a transporter that is important for this (NHE3). K+ is also transported at varying levels within the distal tubule, depending on the amount over the body’s requirement. These secreted substances eventually make their way into urine and are excreted from the body.
Tubular Reabsorption and Secretion to Control pH
The next chapter will go over how the kidney regulates acid-base balance, but first, it’s important to understand the reabsorptions and secretion mechanisms that the kidney employs to keep this balance.
The kidney can deaminate the amino acid glutamine. As NH2 from the amino acid is converted into NH3 and pumped into the PCT lumen, Na+ and HCO3– are excreted into the renal pyramid interstitial fluid via a symport mechanism. When this process occurs in the PCT cells, there is a net loss of a hydrogen ion (complexed to ammonia to form the weak acid NH4+) in the urine and a gain of a bicarbonate ion (HCO3–) in the blood. In a one-to-one exchange, ammonia and bicarbonate are exchanged. This exchange is another way for the body to buffer and excrete acid.
Solutes move across the membranes of the collecting duct cells, which are divided into two types: principal cells and intercalated cells. A principal cell contains sodium and potassium recovery and loss channels. Acid or bicarbonate is secreted or absorbed by an intercalated cell. In the membranes of these cells, as in other parts of the nephron, there is a slew of micromachines (pumps and channels). The DCT and collecting ducts are made up of two types of cells: principal cells and intercalated cells. The primary cells regulate sodium and potassium balance. Intercalated cells play important roles in blood pH regulation. While secreting H+, intercalated cells reabsorb K+ and HCO3–. This function increases the acidity of the urine while decreasing the acidity of the plasma.
Because bicarbonate (HCO3–) is a very powerful and fast-acting buffer, its recovery is critical to maintaining acid-base balance. This mechanism is catalysed by an important enzyme called carbonic anhydrase (CA). This enzyme and reaction are also used in red blood cells to transport CO2, in the stomach to produce hydrochloric acid, and in the pancreas to produce HCO3– to buffer acidic chyme from the stomach. The majority of the CA in the kidney is found within the cell, but a small amount is bound to the brush border of the membrane on the cell’s apical surface. HCO3– combines with hydrogen ions in the PCT lumen to form carbonic acid (H2CO3). This is enzymatically catalysed into CO2 and water, which diffuse into the cell through the apical membrane. Because of the presence of aquaporin water channels, water can move osmotically across the lipid bilayer membrane. The reverse reaction occurs within the cell to produce bicarbonate ions (HCO3–). These bicarbonate ions are co-transported across the basal membrane with Na+ to the interstitial space surrounding the PCT (Figure 25.5.4). At the same time, a Na+/H+ antiporter excretes H+ into the lumen while recovering Na+. Take note of how the hydrogen ion is recycled for bicarbonate to be recovered. It’s also worth noting that the Na+/K+ pump generates a Na+ gradient.
Conclusion
Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, implying that dysfunctional secretion has serious clinical consequences. Tubular secretion measurement as an independent marker of kidney function may provide insight into the aetiology of kidney disease and improve the prediction of adverse outcomes. Tubular secretion is the process by which materials are transferred from peritubular capillaries to the renal tubular lumen; it is the inverse of reabsorption. Active transports and passive diffusions are the primary cause of the secretion. The movement of molecules through ATPase pumps transports the substance through the renal epithelial cell into the nephron lumen. The tubular secretion of H+ and NH4+ from the blood into the tubular fluid regulates blood pH. The movement of these ions also aids in the conservation of sodium bicarbonate (NaHCO3). Urine typically has a pH of around 6, whereas blood should have a pH of 7 to 7.