Tubular Reabsorption

Drugs are reabsorbed into the systemic circulation via the lumen of the distal tubules in a passive process known as tubular reabsorption. Only un-ionized molecules are available for reabsorption, as with enteral absorption. As a result, drugs that change the pH of the urine may cause increased tubular reabsorption of other drugs. Phenobarbital, a mildly acidic drug, is a common example. In overdose cases, sodium bicarbonate is given to alkalinize the urine in the hope that phenobarbital will become more ionised in urine, resulting in less tubular reabsorption and faster excretion. However, the efficacy of this practice is unclear.

Tubular Reabsorption

The second major step in the formation of urine is tubular reabsorption. The proximal part of the tubule is where most of the reabsorption of solutes required for normal body function, such as amino acids, glucose, and salts, occurs. This reabsorption can be active, as in the case of glucose, amino acids, and peptides, or passive, as in the case of water, chloride, and other ions. Water and ion reabsorption also occurs in the distal tubule and the collecting duct.

Xenobiotic resorption is typically passive and governed by the same principles that govern their passage across any membrane. That is, lipophilic compounds cross cell membranes faster than polar compounds; thus, lipophilic toxicants are more likely to be passively reabsorbed than polar toxicants, facilitating the elimination of polar toxicants and their polar metabolites.

Filtrate

The filtrate, or fluid filtered from the blood, passes through the nephron, and much of the filtrate and its contents are reabsorbed into the body. Reabsorption is a finely tuned process that is altered to maintain blood volume, blood pressure, plasma osmolarity, and blood pH homeostasis. Fluids, ions, and molecules that have been reabsorbed are returned to the bloodstream via the peritubular capillaries and are not excreted as urine.

Mechanisms of Reabsorption

Tubular secretion:

The basic physiologic mechanisms of the kidney and the three steps involved in urine formation are depicted in this diagram. Filtration, reabsorption, secretion, and excretion are the four processes. 

Reabsorption in the nephron can be either passive or active, and the specific permeability of each part of the nephron varies greatly depending on the amount and type of substance reabsorbed. The following are the mechanisms of reabsorption into the peritubular capillaries:

Passive diffusion occurs when concentration gradients pass through the plasma membranes of kidney epithelial cells.

Active transport involves membrane-bound ATPase pumps (such as NA+/K+ ATPase pumps) and carrier proteins that use ATP to transport substances across the plasma membranes of kidney epithelial cells.

Cotransport—this process is especially important for water reabsorption. Water can be followed by other molecules that are actively transported, such as glucose and sodium ions in the nephron.

The substance passes through the luminal barrier and the basolateral membrane, two plasma membranes of kidney epithelial cells, and into the peritubular capillaries on the other sides. Some substances can also pass through tight junctions, which are tiny spaces between renal epithelial cells.

Osmolarity Changes

The osmolarity (ion concentration) of filtrate changes as it passes through the nephron as ions and water are reabsorbed. The osmolarity of the filtrate entering the proximal convoluted tubule is 300 mOsm/L, which is the same as the osmolarity of normal plasma.

All of the glucose in a filtrate is reabsorbed in the proximal convoluted tubules, along with an equal concentration of ions and water (via cotransport), so that the filtrate is still 300 mOsm/L as it exits the tubule. As water passes through the descending loop of Henle, which is ion-impermeable, the filtrate osmolarity falls to 1200 mOsm/L. Osmolarity falls to 100–200 mOsm/L in the ascending loop of Henle, which is permeable to ions but not water.

Finally, depending on the hormonal stimulus, a variable amount of ions and water are reabsorbed in the distal convoluted tubule and collecting duct. The final osmolarity of urine is thus determined by whether or not the final collecting tubules and ducts are permeable to water, which is controlled by homeostasis.

Renal tubular disorders

The physiology of the renal tubule, as well as the diseases that can affect its function, are frequently thought to be complicated and perplexing. This article will attempt to simplify tubular disorders by connecting the physiology of the four major nephron segments with the clinical features of the most commonly encountered renal tubular disorders.

The proximal tubule

The proximal convoluted tubule (PCT) is the primary site of active transport and reabsorption of the majority of solutes found in the glomerular filtrate, as well as the site of production of the key urinary buffer ammonium (NH4+):

Reabsorbed solutes in the early part of the PCT (S1) include glucose, amino acids, phosphate, bicarbonate, and various filtered low molecular weight proteins.

Urate is reabsorbed and secreted later in the PCT (S2), and citrate is also reabsorbed.

The proximal straight tubule (S3) is located further along and is where many drugs and their metabolites are secreted (eg loop and thiazide diuretics).

All of this active transport is dependent on the sodium pump’ (Na+K+–ATPase) on the proximal tubular cell’s basolateral side (PTC). This requires energy, so PTCs are full of mitochondria and rely heavily on aerobic respiration, making them vulnerable to hypoxia. This is one of the reasons why PTCs are especially vulnerable to injury or necrosis from renal ischaemia and drug nephrotoxicity.

Disturbance of active transport processes

Failure of these active transport processes in the PTCs results in decreased reabsorption of the previously mentioned solutes, which can then be found in the final urine.

Glucose. Several genetic defects affect glucose (isolated renal glycosuria) and amino acid transport, including cystine (dimeric cysteine) in cystinuria, one of the most common clinically significant inherited amino acid transport defects causing stones in humans. Cystinuria must be distinguished from cystinosis, a lysosomal storage disease characterised by intracellular cystine accumulation.

Bicarbonate. Proximal renal tubular acidosis is caused by a disruption in bicarbonate reabsorption (pRTA or type 2 RTA). Urine pH will initially be alkaline, and systemic bicarbonate concentration will fall, resulting in acidosis. When the bicarbonate reabsorption threshold is reached (usually at a plasma or serum concentration of around 16 mmol/l), any bicarbonate that is not reabsorbed by the PCT is reabsorbed by the thick ascending limb of the loop of Henle and the collecting duct (commonly referred to as the distal nephrons). This reduces further bicarbonate loss, and the urine pH becomes more acidic, as opposed to distal RTA – see below. This type of RTA can occur as an isolated monogenic form1 and can also be caused by carbonic anhydrase inhibitors (for example, acetazolamide) or derivative drugs like the anticonvulsant topiramate.

Conclusion

Drugs are reabsorbed into the systemic circulation via the lumen of the distal tubules in a passive process known as tubular reabsorption. Only un-ionized molecules are available for reabsorption, as with enteral absorption. This reabsorption can be active, as in the case of glucose, amino acids, and peptides, or passive, as in the case of water, chloride, and other ions. Water and ion reabsorption also occurs in the distal tubule and the collecting duct. . Reabsorption is a finely tuned process that is altered to maintain blood volume, blood pressure, plasma osmolarity, and blood pH homeostasis. Reabsorption in the nephron can be either passive or active, and the specific permeability of each part of the nephron varies greatly depending on the amount and type of substance reabsorbed. The osmolarity of the filtrate entering the proximal convoluted tubule is 300 mOsm/L, which is the same as the osmolarity of normal plasma. The final osmolarity of urine is thus determined by whether or not the final collecting tubules and ducts are permeable to water, which is controlled by homeostasis.