Distal nephron

Cortisol-Cortisone Conversion. Under normal conditions, this equilibrium slightly favors the oxidized compound. Similarly, the conversion of corticosterone to 11-deoxycorticosterone is also mediated by the liP-hydroxysteroid dehydrogenase enzyme system and requites NAD(P) /NAD(P)H. This conversion is especially important both in the protection of the human fetus from excessive glucocorticoid exposure, and in the protection of distal nephron mineral ocorticoid receptors from glucocorticoid exposure (14). The impairment of this conversion is thought to result in hypertension associated with renal insufficiency (15). 

ENaC is located in the apical membrane of polarized epithelial cells where it mediates Na+ transport across tight epithelia [3], The most important tight epithelia expressing ENaC include the distal nephron of the kidney, the respiratory epithelium, and the distal colon. The basic function of ENaC in polarized epithelial cells is to allow vectorial transcellular transport of Na+ ions. This transepithelial Na+ transport through a cell involves... 

Epithelial Na Channel. Figure 1 Transepithelial ion transport in a principal cell of the aldosterone-sensitive distal nephron (ASDN). 

In the aldosterone-sensitive distal nephron (ASDN), ENaC-mediated Na+ absorption under the control of aldosterone is critical to balance urinary Na+ excretion with the daily intake. ENaC allows Na+ entry from the tubule lumen at the apical membrane, and the Na+/K.+ ATPase extrudes Na+ at the basolateral side. The Na+ absorption in the distal nephron is coupled to K+ secretion via K+ channels (ROMK2) located at the apical membrane. 

Since the distal nephron reabsorbs under physiological conditions less than 10% of the filtered load of... 

Generalized distal nephron dysfunction (type IV) Mineralocorticoid deficiency or resistance Tubulointerstitial disease Drug-induced hyperkalemia... 

We have tested the hypothesis that insulin inhibits the stimulatory effect of parathyroid hormone (PTH) on calcium reabsorption in the distal nephron. PTH is known to enhance calcium transport in renal cells, probably by stimulation of adenylate cyclase and subsequent increases in 3 5 cyclic AMP productoin. Since insulin had been observed to inhibit PTH-stimulated increases in kidney cyclic AMP levels in vitro (24) we investigated whether insulin-mediated hypercalciuria was dependent on the presence of PTH in vivo. 

Sodium reabsorption Much less than 10% of the filtered load of NaCl reaches the distal nephron. Regulation of Na uptake, occurring mainly in the principal cells of the cortical collecting tubule, is controlled by the steroid hormone aldosterone (see Section 4.4). The net effect of aldosterone is the reclamation of NaCl and potassium excretion in to the luminal fluid. 

Renal 100 F 200 F (distal nephrons with hyaline casts proximal tubules lined with degenerated, necrotic or regenerating epithelium)... 

The dose-response relationship for chloroform-induced cytotoxicity and cell proliferation in the kidneys of female Fisher 344 rats has also been elucidated. Animals received 34, 100, 200, or 400 mg/kg chloroform by gavage in com oil for 4 days. At completion of dosing, kidneys were prepared for microscopic evaluation, and cell proliferation was quantitated. Rats in the high dose group had 50-75% of proximal tubules lined with necrotic or attenuated regenerating epithelium, as well as distal nephrons containing hyaline casts. Rats in the 200 mg/kg group had kidneys with 25-50% of proximal tubules lined with... 

See Table 15-6. Potassium-sparing diuretics are most useful in states of mineralocorticoid excess or hyperaldosteronism (also called aldosteronism), due either to primary hypersecretion (Conn s syndrome, ectopic adrenocorticotropic hormone production) or secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis, nephrotic syndrome, or other conditions associated with diminished effective intravascular volume). Use of diuretics such as thiazides or loop agents can cause or exacerbate volume contraction and may cause secondary hyperaldosteronism. In the setting of enhanced mineralocorticoid secretion and excessive delivery of Na+ to distal nephron sites, renal K+ wasting occurs. Potassium-sparing diuretics of either type may be used in this setting to blunt the K+ secretory response. 

Liddle s syndrome is an autosomal dominant form of hypertension. It is a disorder of the renal epithelial sodium channel, which has three subunits, a, j, and y, and mutations within the first two are associated with increased sodium channel activity [7, 36]. This causes excessive sodium absorption in the distal nephron of the kidney. It gives rise to hypoglycemia, low -renin, and low aldosterone. 

At least three types of ATP driven H+ pumps may be potentially involved in the regulation of pHi. These are (a) an electrogenic H+ translocating ATPase found in the mammalian distal nephron (b) an electroneutral K+-H+ exchange ATPase that is responsible for acid secretion by gastric cells and (c) a vacuolar H+-ATPase which is responsible for the low pH of endocytic vesicles. The vacuolar H+-ATPase can be inhibited by the macrolide antibiotic bafilomycin Al. The gastric K+-H+-ATPase is inhibited by antiulcer drugs such as omeprazole. 

Aldosterone secretion is also stimulated by increased plasma potassium concentration. Potassium is secreted into the urine in exchange for reabsorption of sodium in the distal nephron. Aldosterone also promotes secretion of hydrogen ions from the distal tubule according to the acid-base status of the... 

Q4 Potassium concentration is mainly controlled by the steroid hormone aldosterone. Aldosterone release from the adrenal cortex can be stimulated by either decreased plasma sodium or by increased plasma potassium concentration. An increase in aldosterone secretion causes retention (reabsorption) of sodium in the distal nephron in exchange for secretion of potassium into the urine. The amount of potassium excreted by the kidney is influenced by the acid-base status of the body. In alkalosis, potassium excretion increases, whereas in acidosis it is decreased. In the distal nephron H+ and K+ compete for excretion in exchange for the reabsorption of sodium. Insulin also affects plasma potassium concentration because it promotes the movement of potassium from the plasma into cells. 

Q10 In diabetes insipidus, reabsorption of water in the distal nephron is impaired and a large volume of dilute urine is therefore produced. 

Urinary excretion of water is regulated by ADH /vasopressin, produced in the hypothalamus and released from the posterior pituitary gland. ADH acts on the distal nephron to make this area water-permeable and to allow reabsorption of water. In the absence of ADH the distal nephron is impermeable to water and dilute urine is produced. 

Tubule obstruction. Given certain physicochemical conditions, crystals can deposit within the tubular lumen. Methotrexate, for example, is relatively insoluble at low pH and can precipitate in the distal nephron when the urine is acid. Similarly the uric acid produced by the metabolism of nucleic acids released during rapid tumour cell lysis can cause a fatal urate nephropathy. This was a particular problem with the introduction of chemotherapy for leukaemias until the introduction of allopurinol it is now routinely given before the start of chemotherapy to block xanthine oxidase so that the much more soluble uric acid precursor, hypoxanthine, is excreted instead. Crystal-nephropathy is also a... 

Mild and uncomplicated hyperkalemia is commonly observed in patients taking ciclosporin and is generally prevented by a low potassium diet. A reduction in distal nephron potassium secretion and tubular flow rate, with insensitivity to exogenous mineralocorticoids, and leakage of cellular potassium into the extracellular fluid are possible mechanisms (SED-13, 1124) (64). 

A patient developed acute renal insufficiency after ciprofloxacin overdose. This was mediated by tubulointerstitial nephritis with distal nephron apoptosis, as evidenced by renal biopsy (39). 

However, resistance to loop diuretics can occur by various mechanisms (36). These include poor adherence to therapy, poor absorption, progressive worsening of heart failure, excess volume loss, renal insufficiency, secondary hyperaldosteronism, and hypertrophy of the tubular cells of the distal nephron. Resistance due to inadequate drug absorption—either its speed or extent—is common with furosemide, which is poorly absorbed (34). Once recognized, this hurdle to response can be overcome by using loop diuretics that are predictably well absorbed, such as bumetanide and torasemide or by giving intravenous furosemide (37). 

Proximal tubule Distal nephron Cellular injury ... 

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