Browsing Pathways

The loop of Henle of the nephron can be separated into an ascending limb and the descending limb. The ascending limb is highly impermeable to water, but permeable to solutes. Conversely, the descending limb is highly impermeable to solutes such as sodium, but permeable to water. As solutes are being actively transported out of the ascending limb, the solutes cause in increase in osmotic pressure. This, combined with the ability for water to move freely out of the descending limb, leads to a water reabsorption into the adjacent capillary network and a high concentration of sodium in the filtrate at the descending Limb. Water moves from the descending loop to the capillary network through aquaporin channels in the cell membrane.

The collecting duct of the nephron is the last segment of the functioning nephron and is connected to minor calyces and the ensuing renal pelvis of the kidney where urine continues before it is stored in the bladder. The collecting duct is mainly responsible for the excretion and reabsorption of water and ions. It is composed of two important cell types: intercalated cells that are responsible for maintaining acid-base homeostasis, and principal cells that help maintain the body's water and salt balance. When renin is released from the kidneys, it causes the activation of angiotensin I in the blood circulation which is cleaved to become angiotensin II. Angiotensin II stimulates the release of aldosterone from the adrenal cortex and release of vasopressin from the posterior pituitary gland. When in the circulation, vasopressin eventually binds to receptors on epithelial cells in the collecting ducts. This causes vesicles that contain aquaporins to fuse with the plasma membrane. Aquaporins are proteins that act as water channels once they have bound to the plasma membrane. As a result, the permeability of the collecting duct changes to allow for water reabsorption back into the blood circulation. In addition, sodium and potassium are also reabsorbed back into the systemic circulation at the collecting duct via potassium and sodium channels. However, aldosterone is a major regulator of the reabsorption of these ions as well, as it changes the permeability of the collective duct to these ions. As a result, a high concentration of sodium and potassium in the blood vessels occurs. Some urea and other ions may be reabsorbed as well. The reabsorption of ions and water increases blood fluid volume and blood pressure.

The loop of Henle of the nephron can be separated into an ascending limb and the descending limb. The descending limb is highly impermeable to solutes such as sodium, but permeable to water. Conversely, the ascending limb is highly impermeable to water, but permeable to solutes. Chloride, potassium, and sodium are co-transported across the apical membrane (closest to the lumen) via transporters from the filtrate. The transporter requires all three ions present to be effective and to maintain electroneutrality. In addition, the three ions are transported across the basolateral membrane (closest to the renal interstitium) via other means such as the sodium potassium ATPase transports and the chloride channels in the membrane. As these solutes are being actively transported out of the ascending limb and into the renal interstitium/capillary network without water following (due to the lack of water permeability), the filtrate becomes more diluted. Furthermore, these ions simultaneously causes an increase in osmotic pressure that contributes to water reabsorption in the descending limb. This effect can be magnified with the help of vasopressin, which is a hormone that is typically involved with water reabsorption. However, when it acts on the ascending limb, it aids in increasing sodium reabsorption which will increase water reabsorption in the latter parts of the nephron (the distal tubule and collecting duct).

Kidneys are regulatory organs involved in removing wastes from the blood, hormone production, nutrient reabsorption, and regulating electrolyte concentrations, acid-base balance, extracellular fluid volume, and blood pressure. The early proximal tubule is where glucose, amino acids, sodium, chlorine, phosphate, bicarbonate, and water are reabsorbed. Only water is reabsorbed in the thin descending loop of Henle, while sodium, chlorine and potassium are reabsorbed in the thick ascending loop of Henle. Sodium and chlorine are also reabsorbed in the early distal convoluted tubule. Finally, sodium and water are reabsorbed in the collecting tubules. Blood pressure is regulated by the hormones angiotensin II and aldosterone, which increases sodium chloride reabsorption. This results in an expansion of the extracellular fluid compartment, thus increasing blood pressure.

Insulin is a peptide hormone secreted by the beta islet cells of the pancreas. Insulin acts through receptors and promotes the storage of glucose in the glycogen form. After insulin binding, Insulin Receptor Substrates (IRS) are phosphorylated and act on multiple intracellular pathways. IRS-1 and IRS-2 bind to PI3K subunits to generate PIP3 which recruits proteins such as AKT1 to the membrane, leading to glucose uptake for sucrose metabolism. The AKT1/PI3K/PDK1 complex phosphorylates FOXO family proteins which can alter FOXO nuclear functions. In another pathway, the SHC/IRS-1/GRB2/SOS complex activates HRas proteins to activate MAP kinases such as MAP2K2, ERK1/2, and MAPK1. MAP kinases then function in the nucleus to regulate cell proliferation. MAPK13 is activated by stress and has been shown to inhibit the insulin receptor, leading to insulin resistance.

Insulin is a peptide hormone secreted by the beta islet cells of the pancreas. Insulin acts through receptors and promotes the storage of glucose in the glycogen form. After insulin binding, Insulin Receptor Substrates (IRS) are phosphorylated and act on multiple intracellular pathways. IRS-1 and IRS-2 bind to PI3K subunits to generate PIP3 which recruits proteins such as AKT1 to the membrane, leading to glucose uptake for sucrose metabolism. The AKT1/PI3K/PDK1 complex phosphorylates FOXO family proteins which can alter FOXO nuclear functions. In another pathway, the SHC/IRS-1/GRB2/SOS complex activates HRas proteins to activate MAP kinases such as MAP2K2, ERK1/2, and MAPK1. MAP kinases then function in the nucleus to regulate cell proliferation. MAPK13 is activated by stress and has been shown to inhibit the insulin receptor, leading to insulin resistance.