The distal convoluted tubule (DCT) and collecting duct (CD) are the final two segments of the nephron. They have an important role in the absorption of many ions and in water reabsorption.
The distal convoluted tubule can be subdivided into early and late sections, each with its own functions. This article will consider the functions of both sections of the distal convoluted tubule and the collecting duct.
Early DCT
The role of the early DCT is the absorption of ions, including sodium, chloride, and calcium. It is impermeable to water.
The macula densa are situated in the first segment of the DCT – these are sensory epithelium involved in tubuloglomerular feedback. This tubuloglomerular feedback allows for the control of glomerular filtration rate (GFR) and blood flow within the same nephron. the sente
The movement of these ions is dependent on the Na+/K+-ATPase transporter on the basolateral membrane of the cells. This excretes sodium ions into the extracellular fluid and brings potassium ions into the cell. This channel reduces intracellular sodium levels, creating a gradient that favours the movement of sodium into the cell via other channels on the apical membrane. This process occurs via primary active transport, as ATP is directly needed to set up the gradient.
The sodium concentration gradient generated allows sodium to enter the cell from the lumen of the DCT, which occurs through the NCC symporter (sodium-chloride cotransporter), alongside chloride ions. The chloride ions then exit the cell through a chloride ion uniporter on the basolateral membrane into the extracellular fluid, preventing accumulation within the cell. Thiazide diuretics, used to treat hypertension and heart failure, inhibit the NCC symporter.
Calcium (Ca2+) absorption also utilizes the sodium gradient established from the Na+/K+-ATPase channel. On the basolateral membrane, there is also an NCX channel (sodium-calcium antiporter). This is responsible for transporting calcium ions out into the extracellular fluid, and sodium ions into the cell. The reduction in intracellular calcium creates a gradient that draws calcium ions from the lumen of the tubule into the cell, through a calcium ion uniporter. Since ATP is not directly required, this is secondary active transport. Parathyroid hormone (PTH) also acts here – binding of PTH to its receptor causes more Ca2+ channels to be inserted and increases Ca2+ reabsorption.
Late DCT and CD
There are two main cell types in this region: principal cells and intercalated cells.
Principal Cells
Principal cells make up the majority of the tubular cells. They are mainly involved in the uptake of sodium ions and the extrusion of potassium ions. This exchange is, again, driven by a Na+/K+-ATPase on the basolateral membrane This sets up a gradient for sodium to enter the cell through ENaC channels (epithelial Na+ channel).
Sodium ions are positively charged, so as they are extruded an electrical gradient is formed. Additionally, potassium ions accumulate within the cell due to the Na+/K+-ATPase. Both of these factors promote the secretion of potassium ions into the lumen of the tubule through a potassium uniporter.
Intercalated Cells
Intercalated cells assist in acid-base control, by controlling the levels of hydrogen (H+) and bicarbonate ions (HCO3–). Type A intercalated cells utilise hydrogen-ATPase and H+/K+-ATPase transporters to secrete H+ into the lumen, whilst reabsorbing HCO3–. Bicarbonate is formed intracellularly by carbonic anhydrase acting on carbon dioxide and water (similar to in the PCT).
The difference between the PCT and type A intercalated cells is that these cells can actively secrete H+ into the lumen against a large concentration gradient, allowing for H+ secretion in response to acidosis. Once in the lumen of the tubule, the hydrogen ions react with either phosphate (HPO42-) or ammonia (NH3). This prevents the ions from re-entering the cell, as both new compounds (NH4+ and H2PO4–) are charged. Hence, they are unable to travel back across the membrane, and so are excreted.
To prevent an accumulation of chloride ions and potassium ions within the cell, a K+/Cl– symporter on the basolateral membrane allows leakage of these ions back into the extracellular fluid.
Conversely, type B intercalated cells have H+ and HCO3– channels on opposite sides of the cell. The net effect in type B cells is the secretion of HCO3– and reabsorption of H+, important in the body’s response to alkalosis.
Water Reabsorption in the CD
The main role of the CD is the reabsorption of water, through the action of anti-diuretic hormone (ADH) and aquaporins.
ADH is produced in the hypothalamus, and stored in the posterior pituitary gland until it is released. This hormone acts on kidney tubules to increase the number of aquaporin 2 channels (water channels) in the apical membrane of collecting duct tubular cells.
Fig 1 – Diagram showing the stages through which ADH production and transport occurs.
ADH binds to V2 receptors on the tubule cells, which activate adenylyl cyclase hence increasing the production of cyclic AMP. Subsequently, vesicles containing the aquaporin 2 channels deposit their contents into the apical membrane of the tubular cells (the basolateral membrane always contains aquaporin 3 and 4 channels, so is always permeable).
Increasing the number of channels increases the permeability of the cell, resulting in the ability to reabsorb more water from the filtrate and create smaller volumes of more concentrated urine.
Urea Recycling
ADH also acts to increase urea reabsorption in the medullary collecting duct. The thick ascending limb of the nephron is impermeable to water but permeable to urea. This means that the urea is able to pass from the interstitium back into the thick ascending limb down its concentration gradient (urea recycling). Whilst in the interstitium, urea acts as an effective osmole and hence allows greater volumes of water to be reabsorbed in the nephron.
Fig 2 – Diagram of the complete urea cycle.
Clinical Relevance – Syndrome of Inappropriate Anti-Diuretic Hormone Secretion (SIADH)
This syndrome is where excessive ADH is released. As a result, there is increased aquaporin expression in the collecting duct and excess water retention.
The excessive dilution of blood lowers the sodium concentration and causes hyponatraemia, presenting with symptoms such as nausea, vomiting, and lethargy. Aldosterone secretion is also decreased in response to fluid retention, further reducing sodium uptake in the kidney and thus exacerbating hyponatraemic symptoms.
One potential cause of SIADH is a paraneoplastic syndrome – for example, ectopic ADH secretion from a small cell lung carcinoma. Treatment primarily includes fluid restriction.
Clinical Relevance – Diabetes Insipidus (DI)
This form of diabetes also involves the classic presentation of polyuria (increased frequency of urination), and subsequent polydipsia (excessive thirst). It can be due to either insufficient ADH release from the posterior pituitary gland (central diabetes insipidus), or the collecting ducts not responding to ADH (nephrogenic diabetes insipidus).
If the actions of ADH are ineffective, less water will be reabsorbed from the filtrate. This means there will be a greater volume of filtrate, hence producing a greater volume of urine, causing polyuria and polydipsia.
A water deprivation test can be used as a confirmatory test for diabetes ins, after ruling out other common causes of polydipsia, such as hypercalcaemia. Management depends on the cause; in central DI, desmopressin (synthetic ADH) can be used whilst thiazide diuretics are used in the treatment of nephrogenic DI.