Cortical and medullary collecting duct

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. 

Distribution of the COX-2 isoform in the adult human kidney is based upon in-situ hybridization and immunolocation studies [11]. COX-2 has been detected in both the macula densa and medullary interstitial cells in patients with Bartter s syndrome and congestive heart failure [22] as well as in elderly patients. COX-1, in addition to being expressed in the glomerulus, is constitutively expressed in both the cortical and medullary collecting ducts [15,16] (Figure 2). The exact role of the duel expression of both COX isoforms in the medullary collecting duct remains to be elucidated. 

Under normal conditions, approximately 180 L of glomerular ultrafiltrate are produced per day, the vast majority of which must be reabsorbed by the renal tubules to maintain homeostasis. Clinically, the renal tubule can be divided into three major sections the proximal tubule, Henle s loop, and the distal nephron, which includes the distal tubule, the cortical collecting tubule, and the medullary collecting ducts. In the proximal tubule, approximately 60% to 70% of the filtered load of water and solute is isovolemicaUy reabsorbed, as is the vast majority of filtered amino acids, glucose, and bicarbonate. 

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 . 

The collecting duct system (connecting tubule, initial collecting tubule, cortical collecting duct, and outer and inner medullary collecting ducts) is an area of fine control of ultrafiltrate composition and volume and is where final adjustments in electrolyte composition are ttuide. In addition, vasopressin (also called antidiuretic hormone see Chapter 29) modulates water permeability of this part of the nephron. 

Other renal actions mediated by receptors include increased urea transport in the inner medullary collecting duct and increased Na+ transport in the thick ascending limb both effects contribute to the uiine-concentrating abihty of the kidney (Figure 29-4). receptors also increase Na+ transport in the cortical collecting duct, which may synergize with aldosterone to enhance Na+ reabsorption during hypovolemia. 

The renal medulla is the middle portion of the kidney and consists of the loops of Henle, vasa recta, and collecting ducts. Medullary blood flow (about 6% of total renal blood flow) is considerably lower than cortical flow. However, by virtue of its countercurrent arrangement between tubular and vascular components, the medulla may be exposed to high concentrations of toxicants within tubular and interstitial structures. 

Four factors contribute to the ability to concentrate urine (1) Active reabsorption of Na+, K+, and CF without water reabsorption by the thick ascending limb of the loop of Henle results in interstitial hypertonicity and hypoosmotic tubular fluid. (2) Selective permeability to water, but not small electrolytes, in the descending thin limb of the loop of Henle allows passive reabsorption of water, facilitated by interstitial hypertonicity. (3) Relatively low medullary blood flow maintains medullary hypertonicity, allowing continued elaboration of concentrated urine. (4) In the presence of ADH, the distal tubule and collecting ducts are permeable to water so that water may diffuse out of the tubular lumen into the medullary, and papillary inter-stitium. Because of the ability of the thick ascending limb of the loop of Henle to move solutes but not water into the medullary interstitium, the medullary, and papillary interstitium are hyperosmotic and hypertonic compared to plasma and cortical interstitium (Figure 29.5). 

Tacrolimus may induce tubular dysfunction characterized as an increased excretion of urinary enzymes, decreased urinary concentrating ability, increased fractional excretion of magnesium in the presence of hypomagnesemia, hyperkalemia, hyperuricemia and fubular acidosis [12,260,645,647,705,736,737. In vitro sfudies showed fhat TAC inhibit Na/K - ATPase in rat microdissected cortical collecting duct and medullary thick ascending limb [738], and that high TAC doses added to primary human proximal tubules cultures decreased cell proliferation after 72 hours of incubation... 

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