Thick ascending limb

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... 

The physiological role of the ICOR is not clear and may be heterogeneous in the various tissues. In the thick ascending limb of the loop of Henle this channel appears to serve as the exit for CP at the basal cell pole [16,65,66], This conductive mechanism, therefore, is required for the reabsorption of Na and CP by this segment of the nephron [16]. In the rectal gland of Squalus acanthias a very similar channel is utilized for Na" and CP secretion. In these latter cells the CP-channel is present in the luminal membrane and is controlled by cytosolic cAMP [15,56,71]. It has been claimed that this kind of channel is also responsible for the secretion of CP in the colonic crypt cell, in colonic carcinoma cells and in respiratory epithelial cells [17,19,20,22]. Recent data have cast some doubt on this concept ... 

Several studies have been performed in the laboratory of my colleagues and I [41,70,91-93]. In one of these, starting with the structure of A9C (Fig. 2), the inhibitory effect on the Cl -conductance in thick ascending limb (TAL) segments has been examined. It was found that DPC was much more potent than A9C [41]. In a subsequent study on the same preparation more than 100 relatives of DPC... 

The answer is b. (Hardman, p 697.) The primary action of furosemide is inhibition of the Na+,K+,C1 transporter in the thick ascending limb of the loop of Henle. 

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. 

Thick ascending limb This limb is also impermeable to water. It contains ion pumps to pump electrolytes actively into the interstitium. The main pump is the Na+/2C1 /K+ co-transporter. Fluid leaving this limb is, therefore, hypotonic and passes into the distal convoluted tubule. 

PCT is proximal convoluted tubule, DL is descending limb of the loop of Henle, Thin AL is thin ascending limb of the loop of Henle, Thick AL is thick ascending limb of the loop of Henle, DCT is distal convoluted tubule and CD is collecting duct. (This figure is reproduced with permission from Fundamental Principles and Practice of Anaesthesia, P. Hutton, G. Cooper, F. James and J. Butterworth. Martin-Dunitz 2002 pp. 487, illustration no. 25.16.)... 

Pharmacology Thiazide diuretics increase the urinary excretion of sodium and chloride in approximately equivalent amounts. They inhibit reabsorption of sodium and chloride in the cortical thick ascending limb of the loop of Henie and the early distal tubules. Other common actions include Increased potassium and bicarbonate excretion, decreased calcium excretion and uric acid retention. At maximal therapeutic dosages all thiazides are approximately equal in diuretic efficacy. 

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+... 

Na+-K+-2Ct cotransport In thick ascending limbs. This transport protein is shown by the open circle on the apical cell membrane. Although K+ enters the cell on the cotransporter, little net K+ reabsorption occurs because much of the K+ is recycled back to the urine from the cell. 

The reabsorption of NaCl by the thick ascending limb is not accompanied by water because of the low hydraulic permeability of this nephron segment. Consequently, the tubular fluid becomes dilute as it passes through the thick ascending limbs. This process contributes to normal urinary dilution. Moreover, when Na+ transport in thick ascending limbs is inhibited, urinary dilution will diminish. 

Sodium reabsorption continues in the distal convoluted tubule, which accounts for some 6 to 8% of the transport of sodium. The entry of Na+ across the apical cell membrane is mediated by Na+-Cl cotransport (Fig. 21.4). This protein is a distinct gene product that differs from the Na -K+-2C1 cotransporter in thick ascending limbs. 

D. Increased Na+ excretion is a direct consequence of diuretic treatment. In thick ascending limbs, the site of furosemide action, calcium and magnesium transport is largely determined by the magnitude of... 

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

These are the most efficacious agents available for inducing marked water and electrolyte excretion. The peak diuresis is far greater than that observed maximally with other diuretics. The drugs in this group include furosemide, bumetanide and ethacrynic acid and the main site of action is the thick ascending limb of loop of Henle, thus they are often called loop diuretics. ... 

The reabsorption of Na+ in the thick ascending limb is facilitated by a symporter (Figure 12.3). The symporter actively transfers Na+/K+/2CI- ions into the tubular cell against a concentration gradient. The Na+ ions are then transported out of the cell and into the ECF by the Na+/K+ pump as in the proximal cell. 

Furosemide Loop diuretic Decreases NaCI and KCI reabsorption in thick ascending limb of the loop of Henle in the nephron (see Chapter 15) Increased excretion of salt and water reduces cardiac preload and afterload reduces pulmonary and peripheral edema Acute and chronic heart failure severe hypertension edematous conditions Oral and IV duration 2-4 h Toxicity Hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, sulfonamide allergy... 

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... 

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. 

Ion transport pathways across the luminal and basolateral membranes of the thick ascending limb cell. The lumen positive electrical potential created by K+ back diffusion drives divalent (and monovalent) cation reabsorption via the paracellular pathway. NKCC2 is the primary transporter in the luminal membrane. 

Both the medulla and the cortex of the kidney synthesize prostaglandins, the medulla substantially more than the cortex. COX-1 is expressed mainly in cortical and medullary collecting ducts and mesangial cells, arteriolar endothelium, and epithelial cells of Bowman s capsule. COX-2 is restricted to the renal medullary interstitial cells, the macula densa, and the cortical thick ascending limb. 

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