Henle’s loop

The V2R is expressed in collecting duct cells in rodents it is also expressed in cells of the thick ascending limb of Henle s loop (TAL). V2R-induced Gs-mediated activation of AC, the subsequent increase... 

Eveloff, J., Haase, W. and Kinne, R. (1980). Separation of renal medullary cells isolation of cells from the thick ascending limb of Henle s loop. J. Cell Biol. 87 672-681. 

The smallest functional unit of the kidney is the nephron. In the glomerular capillary loops, ultrafiltration of plasma fluid into Bowman s capsule (BC) yields primary urine. In the proximal tubules (pT), approx. 70% of the ultrafiltrate is retrieved by isoosmotic reabsorption of NaCl and water. In the thick portion of the ascending limb of Henle s loop (HL), NaCl is absorbed unaccompanied by water. This is the prerequisite for the hairpin countercurrent mechanism that allows build-up of a very high NaQ concentration in the renal medulla In the distal tubules (dT), NaCl and water are again jointly reabsorbed. At the end of the nephron, this process involves an aldosterone-controlled exchange of Na+ against 1C or H. In the collecting tubule (C), vasopressin (antidiuretic hormone, ADH) increases the epithelial permeability for water, which is drawn into the hyperosmolar milieu of the renal medulla and thus retained in the body. As a result, a concentrated urine enters the renal pelvis. 

Aquaporin-1, shown here, occurs in the proximal tubule and in Henle s loop. It contains eight transmembrane helices with different lengths and orientations. The yellow-colored residues form a narrowing that only H2O molecules can overcome. 

The functional unit of the kidney is the nephron. It is made up of the Malpighian bodies or renal corpuscles (consisting of Bowman s capsules and the glomerulus), the proximal tubule, Henle s loop, and the distal tubule, which passes into a collecting duct. The human kidney contains around one million nephrons. The nephrons form urine in the following three phases. 

Furosemide is a highly effective and quick-acting diuretic whose action, hke all of the examined loop diuretics, is associated with blocking reabsorption of ions in the ascending bend of Henle s loop. It is used for edema syndrome of various origins, edema of the lungs and brain, chronic renal insufficiency, some forms of hypertonic crises, and poisoning by barbiturates and other compounds excreted mainly with urine. 

These potent diuretic agents interact with almost the entire nephron, including Henle s loop (Fig. 7). Their primary effect is probably the inhibition of the active reabsorption of chloride ions, which then leads to the enhanced excretion of sodium ions and water. Plasma volume is reduced as a result of these effects, whereas in the long-term both cardiac preload and afterload will diminish. The metabolic side-effects of the loop diuretics are globally the same as those of the thiazides, with some incidental differences. Plasma renin activity increases by loop diuretic treatment and it can be well imagined that this effect is noxious in the long-term management of heart failure. The loop diuretics provoke a clearly... 

The thick ascending limb is a major site of salt absorption and a principal locus of action of an important group of diuretics. Approximately 25% of the filtered sodium is reabsorbed by the thick ascending limb of Henle s loop. Sodium transport in this nephron segment is mediated by Na+-K+-2C1 cotransport (Fig. 21.3). This transporter is present only on the apical, or urine, side of the tubule cells. Although K+ is taken up by the transporter, little net K+ reabsorption occurs in the thick ascending limb because much of the absorbed K+... 

D) Increased reabsorption of sodium downstream to the thick ascending limb of Henle s loop... 

Thick ascending limb of Henle s loop (TAL) Active reabsorption of 15-25% of filtered Na+/ K+/ Cl secondary reabsorption of Ca2+ and Mg2+ Very low Na/K/2CI (NKCC2) Loop diuretics... 

At the boundary between the inner and outer stripes of the outer medulla, the proximal tubule empties into the thin descending limb of Henle s loop. Water is extracted from the descending limb of this loop by osmotic forces found in the hypertonic medullary interstitium. As in the proximal tubule, impermeant luminal solutes such as mannitol oppose this water extraction. The thin ascending limb is relatively water-impermeable. 

The thick ascending limb (TAL) of the loop of Henle actively reabsorbs NaCI from the lumen (about 25% of the filtered sodium), but unlike the proximal tubule and the thin descending limb of Henle s loop, it is nearly impermeable to water. Salt reabsorption in the TAL therefore dilutes the tubular fluid, and it is called a diluting segment. Medullary portions of the TAL contribute to medullary hypertonicity and thereby also play an important role in concentration of urine by the collecting duct. 

Only about 10% of the filtered NaCI is reabsorbed in the distal convoluted tubule (DCT). Like the TAL of Henle s loop, this segment is relatively impermeable to water and NaCI reabsorption further dilutes the tubular fluid. The mechanism of NaCI transport in the DCT is an electrically neutral thiazide-sensitive Na+ and cotransporter (NCC, Figure 15-4). 

Because Henle s loop is indirectly responsible for water reabsorption by the downstream collecting duct, loop diuretics can cause severe dehydration. Hyponatremia is less common than with the thiazides (see below), but patients who increase water intake in response to hypovolemia-induced thirst can become severely hyponatremic with loop agents. Loop agents are sometimes used for their calciuric effect, but hypercalcemia can occur in volume-depleted patients who have another—previously occult—cause for... 

The proximal tubule and descending limb of Henle s loop are freely permeable to water (Table 15-1). Any osmotically active agent that is filtered by the glomerulus but not reabsorbed causes water to be retained in these segments and promotes a water diuresis. Such agents can be used to reduce intracranial pressure and to promote prompt removal of renal toxins. The prototypic osmotic diuretic is mannitol. 

Na/K/2CI transporter in the ascending limb of Henle s loop excretion, some wasting, hypokalemic metabolic alkalosis, increased urine Ca and Mg peripheral edema, hypertension, acute hypercalcemia or hyperkalemia, acute renal failure, anion overdose duration of action 2-4 h Toxicitiy Ototoxicity, hypovolemia, wasting, hyperuricemia, hypomagnesemia... 

Several heavy metals, particularly lead, are known to cause major adverse effects to the mammalian kidney, resulting in kidney function impairment. Adverse effects to the mammalian kidney caused by lead include lesions on the proximal tubule and Henle s loop, and the presence of lead inclusion bodies. The metal also is known to cause aminoaciduria, phosphaturia, glycosuria, and renal tubular acidosis. Workers associated with lead-smelting industries also have shown kidney cancer. 

Schafer JA, Troutman SL, Andreoli TE (1974) Volume reabsorption, transepithelial potential differences, and ionic permeability properties in mammalian superficial proximal straight tubules. J Gen Physiol 64 582-607 Schlatter E, Greger R, Weidtke C (1983) Effect of high ceiling diuretics on active salt transport in the cortical thick ascending limb of Henle s loop of rabbit kidney. Correlation of chemical structure and inhibitory potency. Pfltigers Arch 396 210-217... 

The efficacy of xipamide is reflected at various sites of the tubule and Henle s loop. It reaches its point of impact at the early-distal tubule - from the peritubular side. With a threshold dose of 5 mg, a dose dependency ranging between 14 and 60 mg is thus produced for the excretion of water and urine when in excess of 80 mg, there are no further effects. The bioavailability is 73% and protein binding 98%. 

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