Tubular reabsorption and secretion

Tubular reabsorption and secretion, including transport processes and proteins: Water and electrolytes like Na+, K+, Ca2+, HCO3-, solutes like glucose and amino acids etc are absorbed back into the peritubular capillaries after they are filtered at the glomerulus. Organic acids and bases and K+ are secreted from the peritubular capillaries into the tubular fluid.

Glucose: Two transporters are important for the reabsorption of glucose - Na+ glucose cotransporter or SGLT at the luminal membrane and the GLUT 1 and 2 on the basolateral membrane. SGLT moves one molecule of glucose along with two molecules of Na+ into the cell by secondary active transport, as the energy needed for the transfer is derived from the Na+ gradient at the cell membrane. The Na+ gradient in turn is maintained by the Na±K+ ATPase pump. GLUT 1 and 2 transfer glucose into the circulation by facilitated diffusion, which does not need ATP. Below plasma glucose concentration of 200mg/dl all of the glucose that is filtered is reabsorbed. Above 200mg/dl, most of the glucose is absorbed but some of it is secreted as glucose transporters are nearing their saturation level. The plasma concentration at which glucose first appears in urine is called the renal threshold for glucose. As glucose concentration exceeds the threshold more and more is excreted in the urine, at about 350mg/dl plasma glucose, all carriers are saturated and no more glucose can be absorbed. This level is called Tm or transport maximum.

When a graph is plotted for glucose excretion and reabsorption against the plasma glucose level, a “splay” is observed. Splay is the region on the curve where the reabsorption is reaching saturation. This will correspond to the first appearance of glucose in urine. It can be explained by low affinity of SGLT for glucose as it reaches the Tm and also because each nephron will have its own Tm for glucose. The Tm for the kidney as a whole depends on the average Tm of all nephrons.
Urea: Urea is reabsorbed as well as secreted by the tubules to some extent. 50% of the filtered urea is absorbed in the proximal tubule (PCT) by simple diffusion. This is guided by the urea gradient. In the thin descending limb of the loop of Henle, urea is secreted into the lumen. The thick ascending limb, distal tubule and cortical and outer medullary collecting ducts are normally impermeable to urea. Under conditions when ADH is high e.g. in dehydration, urea transporter called UT1 is activated in the inner medullary collecting ducts. ADH causes reabsorption of approximately 70% of filtered urea.
Organic acids, bases and PAH: PAH is secreted into the tubules by PAH transporter OAT 1 and 3, in the proximal tubule which acts as an antiporter. The same transporter also secretes penicillin and is blocked by probenecid. Weak acids and bases are secreted by the proximal tubule. Their urinary excretion is affected by non-ionic diffusion which is based on the urine pH. In acidic urine, weak acids like aspirin, exist is a unionized form while at alkaline pH, the charged or ionized form is predominant. Urinary excretion is increased when weak acids and bases are in ionized form. Accordingly, the excretion of aspirin will be higher in alkaline urine and vice versa. Weak bases, like morphine, are charged at acidic pH and unionized at alkaline pH. Urinary excretion of weak bases is increased in an acidic urine and vice versa. Based on this principal, alkalization of urine is used to treat aspirin toxicity.