Sodium chloride reabsorption

Edema due to NSAIDs induced sodium and fluid retention usually occurs in susceptible individuals within the first week of therapy. Furthermore, these effects are reversible when the drug is discontinued. Clinically evident peripheral edema occurs in up to 5% of patients [3], likely as a result of decreased renal blood flow, possible redistribution of intrarenal blood flow, and increased reabsorption of sodium chloride in the thick ascending loop of Henle. In elderly patients this increased sodium chloride reabsorption coupled with increased water reabsorption is more likely to result in the edema. 

The renal saluretic response to loop diuretics is partially dependent on intact intrarenal prostaglandin production in the thick ascending loop of Henle. The decrease in the response to loop diuretics is mediated both by removing the inhibition of sodium chloride reabsorption and an increase in renal medullary blood flow causing a reduction in renal concentrating capacity. The net result is that the concurrent use of a NSAID may blunt the diuresis induced by loop diuretics. 

Thiazides and related diuretics inhibit the reabsorption of sodium and chloride ions in the ascending portion of the loop of Henle and the early distal tubule of the nephron. This action results in the excretion of sodium, chloride, and water. 

Two types of diuretics are used for volume management in HF thiazides and loop diuretics. Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and metolazone block sodium and chloride reabsorption in the distal convoluted tubule. Thiazides are weaker than loop diuretics in terms of effecting an increase in urine output and therefore are not utilized frequently as monotherapy in HF. They are optimally suited for patients with hypertension who have mild congestion. Additionally, the action of thiazides is limited in patients with renal insufficiency (creatinine clearance less than 30 mL/minute) due to reduced secretion into their site of action. An exception is metolazone, which retains its potent action in patients with renal dysfunction. Metolazone is often used in combination with loop diuretics when patients exhibit diuretic resistance, defined as edema unresponsive to loop diuretics alone. 

Prolonged administration of loop diuretics can lead to a second type of diuretic resistance. Enhanced delivery of sodium to the distal tubule can result in hypertrophy of distal convoluted cells.17 Subsequently, increased sodium chloride absorption occurs in the distal tubule which diminishes the effect of the loop diuretic on sodium excretion. Addition of a distal convoluted tubule diuretic, such as metolazone or hydrochlorothiazide, to a loop diuretic can result in a synergistic increase in urine output. There are no data to support the efficacy of one distal convoluted tubule diuretic over another. The common practice of administering the distal convoluted tubule diuretic 30 to 60 minutes prior to the loop diuretic has not been studied, although this practice may first inhibit sodium reabsorption at the distal convoluted tubule before it is inundated with sodium from the loop of Henle. 

Active reabsorption occurs when the movement of a given substance across the luminal surface or the basolateral surface of the tubular epithelial cell requires energy. Substances that are actively reabsorbed from the tubule include glucose amino acids and Na+, POy3, and Ca++ ions. Three generalizations can be made regarding the tubular reabsorption of sodium, chloride, and water ... 

Chloride reabsorption. Chloride ions are reabsorbed passively according to the electrical gradient established by the active reabsorption of sodium. Chloride ions move from the tubular lumen back into the plasma by two pathways ... 

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. 

Of the various solutes reabsorbed in the proximal tubule, the most relevant to diuretic action are sodium bicarbonate and sodium chloride. Of the currently available diuretics, only one group (carbonic anhydrase inhibitors, which block NaHC03 reabsorption) acts predominantly in the proximal tubule. In view of the large quantity of sodium chloride absorbed in the proximal tubule, a drug that specifically blocked reabsorption of this salt at this site might be a particularly powerful diuretic agent. No such drug is currently available. 

Q6 Thiazide diuretics are moderately powerful diuretic agents acting on the distal tubule of the nephron. They reduce reabsorption of sodium chloride and water by blocking the electroneutral sodium chloride (NaCl) transporter system at the luminal border of the distal tubular cells. In addition there are direct relaxant effects on vascular smooth muscle which reduces BP. Diuretics help patients in heart failure by reducing peripheral oedema and decreasing blood volume, which in turn reduces BP. In this way both preload and afterload are decreased and the work of the heart is diminished. 

The surface of the mucosa is relatively smooth as there are no intestinal villi. Crypts of Lieberktlhn are present. Goblet cells account for more of the epithehal cells than in the small intestine. The mammalian large intestine is important for the maintenance of water and electrolyte balance. Its primary function is the reabsorption of water, sodium, chloride and volatile fatty acids it secretes potassium and bicarbonate. 

Although one thiazide diuretic may be 100 times more potent than another weight for weight, all these drugs have essentially the same properties. Their mechanism of action (inhibition of sodium and chloride reabsorption in the distal convoluted tubule of the kidney) is identical and they can therefore be dealt with as a group. Thiazidelike diuretics, structurally different from the thiazides, have similar actions. Thiazide and thiazide-like diuretics are listed in Table 1. 

Oxalate is excreted primarily by the kidney. Oxalate is freely filtered at the glomerulus, where its concentration is normally 1 5 pM. One of the few physiologic functions of oxalate occurs in the proximal tubule where it plays a role in transcellular reabsorption of chloride (mainly present as sodium chloride). Cl entry across the apical membrane is mediated by Cl /oxalate exchange (oxalate is recycled from the tubular lumen to the cell by oxalate/ sulfate exchange, in parallel with Na /sulfate cotransport) [4]. Early studies of renal oxalate clearance using radio-labeled oxalate showed secretion in almost all subjects studied. More recent studies using direct measurement of serum and urine... 

Acetazolamide is the prototype carbonic anhydrase inhibitor and exerts its effects by decreasing the reabsorption of sodium, chloride and bicarbonate in the proximal tubules (Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). Acetazolamide blocks two isoenzymes of carbonic anhydrase, a soluble form... 

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. 

Elevates osmotic pressure of glomerular filtrate, increases flow of water into interstitial fluid and plasma, inhibiting renal tubular reabsorption of sodium, chloride, producing diuresis. Enhances flow of water from eye into plasma, reducing intraocular pressure (IOP)... 

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