The basic functional unit of a kidney is a nephron. The nephron consists of a filtering component known as the renal corpuscle and a renal tubule, which is responsible for absorption and secretion of ions.
The renal tubule can be further divided into components known as the proximal convoluted tubule, the Loop of Henle and the distal convoluted tubule. This article will focus on ion absorption within the proximal convoluted tubule.
The proximal convoluted tubule (PCT) has a high capacity for reabsorption, hence it has specialised features to aid with this. It is lined with simple cuboidal epithelial cells which have a brush border to increase surface area on the apical side. The epithelial cells have large amounts of mitochondria present to support the processes involved in transporting ions and substances.
Moreover, they also have a large number of channels on both the apical and basolateral membrane which provides a large surface area for transport of ions and other substances to occur.
The proximal tubule can be divided into pars convolute and pars recta. The pars convolute resides in the renal cortex and it can further be divided into 2 segments; S1 (segment 1) and the proximal part of S2. The pars recta is a straight segment present in the outer medulla. It makes up the distal part of S2 and S3.
A large amount of reabsorption occurs in the PCT. Reabsorption is when water and solutes within the PCT are transported into the bloodstream. In the PCT this process occurs via bulk transport. The solutes and water move from the PCT to the interstitium and then into peri-tubular capillaries. The reabsorption in the proximal tubule is isosmotic.
The proximal tubules reabsorb about 65% of water, sodium, potassium and chloride, 100% of glucose, 100% amino acids, and 85-90% of bicarbonate. This reabsorption occurs due to the presence of channels on the basolateral (facing the interstitium) and apical membranes (facing the tubular lumen).
There are two routes through which reabsorption can take place: paracellular and transcellular. The transcellular route is transporting solutes through a cell. The paracellular route is transporting solutes through the intercellular space.
The driving force for the reabsorption in the PCT is sodium. On the apical membrane, it is usually co-transported with solutes e.g. amino acids and glucose, or in later segments of the tubule with chloride ions. The S1 segment of the PCT is not permeable to urea and chloride ions, hence their concentration increases in S1 which creates a concentration gradient which can be utilised in the S2 and S3 segments. Additional sodium is transported via a counter-transport mechanism that reabsorbs sodium whilst secreting other ions, especially H+.
On the basolateral side of the PCT cells, the 3Na-2K-ATPase pumps out intracellular Na+ ions. This transporter uses primary active transport. This movement of Na+ creates an electrochemical gradient favouring the movement of Na+ into the cell from the tubule lumen.
Co-transport refers to the movement of multiple solutes through the same channel.
The sodium concentration gradient allows other molecules, such as glucose, to be transported across the apical membrane against their concentration gradient. For example, SGLT transporters move glucose together with two sodium ions across the apical membrane. Glucose then crosses the basolateral membrane via facilitated diffusion.
Na+/Amino acid symporters are present on the apical side of cells in the S1 segment of the PCT which reabsorbs all the amino acids in the PCT.
Na+/H+ antiporter is another protein of the apical side of the cells in the PCT. It is an antiporter, and therefore transports ions across the cell membrane in opposite directions. In this case, the Na+ ions move into the tubular cells and the H+ is expelled into the tubule. The primary function of this transport it to maintain the pH.
Movement of Water
In the PCT, large volumes of solute area transported into the bloodstream. This means that as we move along the tubule, the solute concentrations in the tubule are decreasing while the solute concentrations in the interstitium are increasing.
The difference in concentration gradient results in the water moving into the interstitium via osmosis. Water mainly takes the paracellular route to move out of the renal tubule but it can also take the transcellular route.
Secretion is when substances are removed from the blood and transported into the PCT. This is very useful as only 20% of the blood is filtered in the glomerulus every minute, so this provides an alternative route for substances to enter the tubular lumen. The PCT secretes:
- Organic acids and bases e.g. bile salts, oxalate and catecholamines (waste products of metabolism)
- Hydrogen ions- important in maintaining acid/base balance in the body. H+ secretion allows reabsorption of bicarbonate via the use of the enzyme carbonic anhydrase (Fig 2). The net result is for every one molecule of H+ secreted, one molecule of bicarbonate and Na+ is reabsorbed into the blood stream. As the H+ is consumed in the reaction in the tubular lumen, there is no net excretion of H+. In this way, about 85% of filtered bicarbonate is reabsorbed in the PCT (the rest is reabsorbed by the intercalated cells at the DCT/CD later on)..
- Drugs/toxins: Secretion of organic cations such as dopamine or morphine occurs via the H+/OC+ exchanger on the apical side of the tubule cell, which is driven by the Na+/H+ antiporter.
Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common primary renal malignancy which originates from the PCT. It has been related to alterations in chromosome 3 which can non-hereditary or hereditary. Most commonly it occurs in men between the ages of 50-70.
Incidence of renal cell carcinoma has been linked with smoking and obesity. It can present clinically with haematuria, flank pain, fever and weight loss. It can invade in to the renal vein and then into the inferior vena cava. From here, it can metastasize hematogenously to lung and bones. RCC can also have paraneoplastic effects. In RCC paraneoplastic effects are caused by release of ACTH or PTHrP.
Acute Tubular Necrosis
ATN can be caused by ischaemia which is usually occurs secondary to reduced renal blood flow (for example hypotension or sepsis). It can also be caused by nephrotoxic agents such as aminoglycosides and myoglobin. The ischaemia and toxins results in the death of tubular cells particularly the cells of the PCT.
|Ion channel||Location||Type of Transporter||Pathology|
|3Na-2K-ATPase||Basolateral||Antiporter like activity but it is not an antiporter *|
|Sodium-dependent glucose transporter||Apical
|Symporter||When glucose concentration exceeds the transport maximum, the extra glucose spills into the urine. Since glucose has an osmotic potential water follows the filtrate resulting in polyuria.
|Na+/Amino acid transporter||Apical||Symporter|
Known as ‘gliflozins’ these are relatively new drugs used in the treatment of type 2 diabetes, however recent studies have shown benefit in non-diabetic cardiovascular disease and progression of CKD as well. Inhibition of the SGLT2 transporter leads to glucose being excreted, lowering blood glucose levels and contributing to some weight loss. Side effects include frequent UTIs, fungal infections and reported ‘euglycaemic diabetic ketoacidosis’.