Thick ascending limb nephron

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 ... 

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+... 

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. 

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... 

Cell death induced by AmB in the medullary thick ascending limb is prevented by ouabain [108]. A reasonable explanation for this observation is that ouabain, by inhibiting transport, decreases the oxygen demand of an area of the nephron that already has a hmited oxygen supply. This is consistent with the observation that AmB exhibits preferential damage to the medullary ray, an area that is vulnerable to hypoxic injury [48]. It is also conceivable that AmB-induced renal vasoconstriction and ischemia to this section of the nephron enhances cell death produced by a direct toxic action. Thus, any maneuver that improves renal perfusion, or decreases oxygen demand, would be expected to be protective. This may explain the salutary effect of salt loading, theophylline, calcium channel... 

Figure 10.1 Sites and mechanisms of action of diuretics. The location of each cell type along the nephron is indicated by the shading patterns. Spironoiactone (not shown) is a competitive aldosterone antagonist and acts primarily in the collecting duct. PT, proximal tubule LH, loop of Henie TAL, thick ascending limb DT, distal tubule DCT, distal convoluted tubule CD, collecting duct PC, principal cell CA, carbonic anhydrase CAI, carbonic anhydrase inhibitors , primary active transport. (Adapted with permission from Ellison D H 1991 The physiologic basis of diuretic synergism its role in treating diuretic resistance. Annals of Internal Medicine 114 886-894.)...

Figure 1 Anatomy of the nephron. RC, renal corpuscle (includes glomerulus and Bowman s capsule) PCT, proximal convoluted tubule PST, proximal straight tubule DLH, descending limb of the loop of Henie ALH, ascending limb of the loop of Henie TALH, thick ascending limb of the loop of Henie MD, macula densa DCT, distal convoluted tubule CT, connecting tubule CD, collecting duct.

When the luminal fluid reaches the thick ascending limb of the loop of Henle, water no longer can freely move from the luminal fluid into the medullary interstitial space. Instead, this portion of the nephron is impermeable to water reabsorption and actively reabsorbs sodium, chloride, and potassium ions. Approximately 20-25% of filtered sodium and calcium ions are reabsorbed at this location. In addition, most, if not all, of the potassium ions reaching the thick limb of the loop of Henle are reabsorbed as well. Thus, as the luminal fluid passes through the ascending limb, the luminal fluid becomes more dilute. 

The intracellular negative electrical potential opposes chloride entry into cells. In the early proximal tubule the main cation, sodium, is predominantly reabsorbed concomitantly with bicarbonate so that the luminal chloride concentration actually increases. There are two main reabsorption mechanisms for chloride. The first is via an antipoiter in exchange for secretion of other anions (e.g., bicarbonate) or formate. The second occurs in the final two thirds of the proximal tubule. In the thick ascending limb of the loop of Henle, chloride is reabsorbed in association with sodium via NKCC2. The concentration gradient is maintained by a basolateral chloride pump, CLC-Kb (see Figure 45-7). A further chloride channel, CLC-5, is expressed at multiple sites in the nephron. ... 

The most well-known urinary glycoprotein is the Tamm-Horsfall mucoprotein (THM). It is argued that the THM and uromucoid are both artifacts from the same native precursor and differ only in their sialic acid content (Kl). They are similar immunologically (Kl). The molecular mass of THM is 7 x 106 Da (Tl), with subunits of about 100,000 Da (F3). THM is synthesized by the cells of the thick ascending limb of Henle in the nephron (LI, R3). 

P450 27B1 is expressed in many parts of the human kidney, including the distal convoluted tubule, the cortical and medullary part of the collecting ducts, and the papillary epithelia. Lower expression was observed along the thick ascending limb of the loop of Henle and Bowman s capsule. Some weaker expression was observed in glomeruli or vascular structures. In normal humans, the distal nephron is the predominant site of expression . 

Diluting segment A segment of the nephron that removes solute without water the thick ascending limb and the distal convoluted tubule are active salt-absorbing segments that are not permeable by water... 

Diuretics that increase the detiveiy of poorly absorbed solute to the thick ascending limb of the nephron include... 

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