Potassium reabsorption

Diuretic-induced hyponatremia occurs more frequently in patients treated with thiazide diuretics than in patients who are receiving loop diuretics. In addition to causing extracellular volume depletion and nonosmotic stimulation of ADH, thiazides interfere with urinary dilution and water excretion by blocking tubular sodium and potassium reabsorption in the distal tubule. Water is then retained in excess of sodium by virtue of nonosmotic release of ADH and excretion of urine with a concentration of sodium and potassium that exceeds that of the plasma. 

Spironolactone is the most clinically usehil steroidal aldosterone antagonist, and unlike GR antagonists, this compound is utilized much more frequendy than aldosterone agonists. Interfering with reabsorption and secretion in the late distal segment, this compound is predominantiy used with other diuretics. Canrenone, an olefinic metaboHte of spironolactone, and potassium canrenoate, in which the C-17 lactone has been hydrolyzed open, are also potent mineralocorticoid antagonists. 

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Decrease blood calcium Increase blood calcium decrease blood phosphate activation of vitamin D 3 "Fight-or-flight" response reinforces effects of the sympathetic nervous system Reabsorption of sodium excretion of potassium... 

Potassium-sparing diuretics act on the late portion of the distal tubule and on the cortical collecting duct. As a result of their site of action, these diuretics also have a limited effect on diuresis compared to the loop diuretics (3% of the filtered Na+ ions may be excreted). However, the clinical advantage of these drugs is that the reabsorption of K+ ions is enhanced, reducing the risk of hypokalemia. 

Gorsuch and Hercules 109> stated that certain discrepancies between the fluorescence spectrum of 3-amino-phthalate dianion and the chemiluminescence spectrum of luminol are partly due to reabsorption of the shorter-wavelength chemiluminescence light by the luminol monoanion. These authors confirmed the results of E. H. White and M. M. Bursey 114> concerning the very essential solvent effect on luminol chemiluminescence the relative intensity of the latter in anhydrous DMSO/t-BuOK/ oxygen was found to be about 30,000 times that in DMSO/28 mole % water/potassium hydroxide/oxygen. 

Spironolactone and eplerenone block the mineralocorticoid receptor, the target site for aldosterone. In the kidney, aldosterone antagonists inhibit sodium reabsorption and potassium excretion. However, diuretic effects are minimal, suggesting that their therapeutic benefits result from other... 

Hyperchloremic acidosis has been noted in some cases (B7, K13) this is presumably due to defective tubular reabsorption of bicarbonate. Phosphate-losing rickets or marked hypokalemia have not as yet been reported in galactosemia, but some cases show roentgenological evidence of osteoporosis (M2), and Holzel et al. (H8) record low levels of serum potassium. 

Proximal tubule Cells of the PCT are responsible for bulk transport of solutes, with approximately 70-80% of the filtered load of sodium chloride (active processes) and water (passive, down the osmotic gradient established by sodium reabsorption) and essentially all of the amino acids, bicarbonate, glucose and potassium being reabsorbed in this region. 

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. 

These results suggest acute renal failure (ARF) due to tubular necrosis caused by phenol. Plasma sodium is low due mainly to impaired reabsorption in the nephron, although the slightly low albumin suggests haemodilution possibly as a result of excessive i.v. fluids. Potassium is raised due to poor exchange with sodium in the distal tubule and the acidosis (low pH and low bicarbonate concentration) arises from defective acidification of the glomerular filtrate acidosis is often associated with hyperkalaemia (raised plasma... 

The nephronic parts of the kidney are the principal diuretic active sites for secreting ede-matic fluid from the organism. Diuretics basically increase secretion of water and salts from the kidneys by suppressing reabsorption of a few main ions (primarily sodium and chloride ions) however, secretion of calcium, potassium, magnesium, and hydrocarbonate ions also increases to some degree. 

Acetazolamide is an aromatic sulfonamide used as a carbonic anhydrase inhibitor. It facilitates production of alkahne urine with an elevated biocarbonate, sodium, and potassium ion concentrations. By inhibiting carbonic anhydrase, the drug suppresses reabsorption of sodium ions in exchange for hydrogen ions, increases reflux of bicarbonate and sodium ions and reduces reflux of chloride ions. During this process, chloride ions are kept in the kidneys to cover of insufficiency of bicarbonate ions, and for keeping an ion balance. Electrolytic contents of fluid secreted by the kidneys in patients taking carbonic anhydrase inhibitors are characterized by elevated levels of sodium, potassium, and bicarbonate ions and a moderate increase in water level. Urine becomes basic, and the concentration of bicarbonate in the plasma is reduced. 

Triamterene is a pyrazine derivative that inhibits reabsorption of sodium ions without increasing excretion of potassium ions. It exhibits the same approximate effect as spironolactone however, it does not competitively bind with aldosterone receptors. Its action does not have an effect on secretion of aldosterone or its antagonists, which are a result of direct action on renal tubules. 

Amyloride is also a potassium sparing diuretic that exhibits moderate activity. It is not an antagonist of aldosterone. It inhibits reabsorption of sodium ions and reduces excretion of... 

Desoxycorticosterone causes an increase in reabsorption of sodium ions and excretion of potassium ions from the renal tubules, which leads to increased tissue hydrophilicity. This facilitates an elevated volume of plasma and increased arterial pressure. Muscle tonicity and work capability are increased. It is used for an insufficiency of function of the adrenal cortex, myasthenia, asthenia, adynamia, and overall muscle weakness. Synonyms of this drug are percorten, docabolin, cortitron, and others. 

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. 

Amiloride and triamterene-Am or 6e and triamterene not only inhibit sodium reabsorption induced by aldosterone, but they also inhibit basal sodium reabsorption. They are not aldosterone antagonists, but act directly on the renal distal tubule, cortical collecting tubule and collecting duct. They induce a reversal of polarity of the transtubular electrical-potential difference and inhibit active transport of sodium and potassium. Amiloride may inhibit sodium, potassium-ATPase. 

Potassium-sparing diuretics, such as amiloride and triamterene. These agents reduce at the tubular level the reabsorption of sodium and water, whereas the excretion of potassium is diminished. Their primary effects are independent of aldosterone. They are slow-acting and weak diuretics, which are unsuitable as monotherapy of hypertension or heart failure. For this reason, they are always combined with thiazide or loop diuretics. Several combined preparations are commercially available. 

Aldosterone stimulates the rates of Na+ reabsorption and K+ secretion. This is relevant to the action of spironolactone, a diuretic that is a competitive inhibitor of aldosterone (discussed later). It is also pertinent because administration of diuretics can cause secondary hyperaldosteronism, which may exaggerate the potassium wasting that is a consequence of the increased delivery of Na+ and enhanced flow through distal convoluted tubules and collecting ducts. 

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