To be reabsorbed into the blood, substances in the filtrate must cross the barrier formed by the tubular cells. There are two reabsorption pathways: the transcellular and the paracellular. Most solutes that are reabsorbed use the transcellular pathway. They diffuse, or are actively transported, through the luminal and basolateral membranes of the tubular cells into the interstitial space and then into the peritubular capillaries. The second pathway is the paracellular one through the tight junctions into the lateral intercellular space. Certain tight junctions are not as tight as the name implies and will allow this pathway while others will not. Although most substances use the transcellular pathway, water and certain ions use both paths, especially in the proximal convoluted tubule. Both pathways lead into the interstitial space, then through the endothelium of the peritubular capillaries into the blood. The previous topic, glomerular filtration, demonstrated that the force driving the formation of the filtrate is blood pressure within the glomerulus. We now turn to the question of what drives reabsorption, which reclaims the valued substances. Letâs begin with the reabsorption of water by diffusion. Increasing the osmolarity of the interstitium, causes water to diffuse from the lumen through the tight junctions of the tubular cells into the interstitial space. Water will move from its higher concentration in the tubule through the tight junctions to its lower concentration in the interstitium. Water will also move through the plasma membranes of the cells that are permeable to water. One method to increase the osmolarity of the interstitium is through the active transport of sodium ions. Sodium ions are pumped into the interstitium from the basolateral membrane. As the interstitial osmolarity increases, water will diffuse out of the tubular lumen and into the interstitium, equilibrating the two osmolarities. Meanwhile, the lowered intracellular sodium ion concentration causes additional sodium ions to be reabsorbed through the luminal membrane. This provides more sodium ions to be actively transported and enables the cycle to repeat. As we will see in the following sections, sodium ion transport also enables the reabsorption of most substances in the nephron. We will now begin a tour through the renal tubules. Weâll see how the specialized cells in each region accomplish a different stage of filtrate processing. Our first stop is the proximal convoluted tubule where major reabsorption of valued substances occurs. Weâll look first at the activities occurring at the basolateral membrane of the tubular cells. The reabsorption of many substances from the glomerular filtrate in the PCT depends directly or indirectly on the active reabsorption of the sodium ion. The cellular structure responsible for this process is the sodium/-potassium ATPase ion pump located in the basolateral membrane. Letâs activate the pump. Using energy from ATP, the ion pump carries out primary active transport of sodium ions out of the cell and potassium ions into the cell. As it yields its energy, ATP is converted to ADP and an inorganic phosphate iron, or P-i. The sodium or potassium pump is found in the basolateral membrane of many regions of the nephron. Watch what happens to the fluid in the interstitial space as a result of the iron pumpâs activity. Notice that the interstitial fluid is becoming more concentrated as indicated by the darker color. The net effect of the ion pumps activity is to decrease the sodium ion concentration inside the cell and increase its concentration outside the cell. Thereby increasing the interstitial osmolarity. However, this increased osmolarity around the PCT soon draws water from the tubule, decreasing the interstitial osmolarity again, and together, the water and solutes diffuse passively into the peritubular capillaries and are carried away. Now notice two additional transmembrane proteins in the basolateral membrane, a potassium ion channel and a glucose carrier molecule. The potassium ion channel lets most of the potassium ions diffuse from the tubular cells back into the interstitium. It prevents the sodium or potassium ATPase ion pump from causing potassium ion depletion in the blood or excess accumulation in the cells. Now letâs look at the glucosecarrier molecule activity. The glucose carrier molecule binds only to glucose and transports it across the basolateral membrane by a passive mechanism called facilitated diffusion. Glucose can move either into or out of the cell depending on its concentration. Since, in the situation shown here, its concentration is highest in the cell, glucose moves out of the cell into the interstitium. In addition to the molecule you see here, many other substances also cross the basolateral membrane by similar mechanisms. The luminal membrane of the proximal convoluted tubule contains many transport proteins. Here you see three sodium-hydrogen countertransport carrier molecules, and two sodium glucose cotransport carrier molecules. The activity of all these carrier molecules depends on sodium-potassium ATPase ion pump activity in the basolateral membrane. The countertransport, or antiport, carrier molecules carry a sodium ion into the cell and in exchange, secrete a hydrogen ion into the filtrate. The hydrogen ion is generated in the cell for acid-based balancing purposes. The movement of the hydrogen ion out of the cell is an example of secondary active transport. It is driven by the primary active transport of the sodium ion into the cell, down its concentration gradient. The cotransport, or symport, carrier molecules carry both sodium and glucose into the cell. The reabsorption of glucose is also an example of secondary active transport. It depends on the movement of the sodium ion down its concentration gradient from high extracellular to low intracellular concentrations. The glucose now moves down its concentration gradient to the basolateral membrane where it is transported into the interstitium by facilitated diffusion as seen previously. This animation shows only a few of the molecules that cross the luminal membrane of the PCT. Although not shown here, water and many other solutes diffuse or are actively transported through the luminal membrane for reabsorption back into the blood. For most actively reabsorbed solutes, the amount reabsorbed in the PCT is limited only by the number of available transport carriers for that specific substance. This limit is called the transport maximum or Tm. If the amount of a specific solute in the filtrate exceeds the transport maximum, the excess solute continues to pass unreabsorbed through the tubules and is excreted in the urine.