China
Africa
Explore chapters and articles related to this topic
Role of Metabolism in Chemically Induced Nephrotoxicity
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
An additional factor that must be considered is that of the regional heterogeneity in the kidney. The mammalian nephron is composed of several cell types that differ from one another structurally, biochemically, and functionally (Guder and Ross, 1984; Mohandas et al., 1984; Walker and Valtin, 1982). Each cell type possesses a distinct complement of metabolic and drug-metabolism pathways, indicating that a uniform bioactivation mechanism for a specific chemical may not apply for all regions of the nephron. Rather, one mechanism may occur in proximal tubular cells and another in the medullary thick ascending limb cells. This biochemical heterogeneity will also likely contribute to the targeting of nephrotoxic chemicals to particular nephron cell types so that a specific chemical may be a potent toxicant in one cell population, but be relatively inert in another cell population (Lash, 1990).
The Loop of Henle and Production of Concentrated Urine
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Active transport of sodium and chloride from the thick ascending limb increases the osmolality of the interstitial fluid and dilutes the fluid within the tubular lumen. Because of the raised interstitial osmolality, water moves out of the descending limb. In the loop of Henle, water reabsorption (descending limb) is separated from sodium and chloride reabsorption (ascending limb). The net result is that the osmolality of both the interstitial fluid and the fluid within the descending limb increases (to 400 mOsm/kg H2O), whereas the osmolality within the ascending limb decreases (to 200 mOsm/kg H2O).
Basic pharmacology of cardiac drugs
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
As noted above, the loop diuretics act primarily to inhibit electrolyte reabsorption in the thick ascending limb of the loop of Henle. They act at the tubular luminal phase to inhibit the Na-K-2Cl co-transport mechanism. They also tend to produce a rapid onset, short-lived increase in renal blood flow which is accompanied by increased excretion of prostaglandins and kinins by the kidney. Parenterally administered frusemide also causes a rapid increase in venous capacitance, which occurs before the diuretic effect, and results in a decrease in cardiac preload and left ventricular filling pressures, which may contribute to the early response seen in patients with pulmonary oedema.
The anti-hypertensive effects of sodium-glucose cotransporter-2 inhibitors
Published in Expert Review of Cardiovascular Therapy, 2023
Luxcia Kugathasan, Lisa Dubrofsky, Andrew Advani, David Z.I. Cherney
Under normal physiological conditions, blocking sodium transport in the proximal tubule increases distal tubular load and promotes a compensatory enhancement of sodium, chloride, and potassium reabsorption at the loop of Henle primarily by Na-K-2Cl (NKCC2) cotransporters. However, owing to the natriuretic-diuretic coupling effect of SGLT2 inhibition at the proximal tubule, it has been postulated that a diluted load with a low chloride concentration is delivered to the distal nephron and renders tubular reabsorption at the loop of Henle ineffective (Figure 3) [96]. Specifically, since the proximal tubule is highly permeable to water and SGLT2 inhibition renders glucose non-resorbable, isotonicity between the tubular fluid and blood is maintained by osmoregulation. The resulting diuresis is thought to decrease the chloride ion concentration in the proximal tubular filtrate [92]. Therefore, it is speculated that the requirement of two chloride ions for each cotransport at the thick ascending limb subsequently reduces NKCC2 cotransporter activity in a diluted chloride environment [92,96]. The off-target impact of SGLT2 inhibitors at the thick ascending limb may indicate similar activity to that of a loop diuretic to promote plasma volume contraction, although this effect has yet to be proven [96].
The role of dietary salt and alcohol use reduction in the management of hypertension
Published in Expert Review of Cardiovascular Therapy, 2021
According to the theoretical description, hypertension could result from a rise in cardiac output or in total peripheral resistance, or both. The evidence has proposed that excessive sodium retention is a contributing factor in genetically predisposed (salt-sensitive) persons [46]. Sodium sensitivity is the responsiveness of BP to the variations in salt ingestion. The degree of BP variation after sudden variations in salt ingestion differs significantly from person to person [161,162]. The diminished kidney sodium excretion can cause the preliminary volume increase and afterward, it will lead to hypertension [163,164]. The way by which sodium reabsorption rise is not well known. The probable mechanism of action includes; the thick ascending limb Na-K-2Cl cotransporter, raised an action of the proximal tubular Na-H exchanger, the distal tubular Na-Cl cotransporter, and the collecting duct epithelial sodium channel [165–167]. The association between hypertension and the activity of the proximal Na-H exchanger has been supported by evidence [166]. The raised action of the epithelial sodium channel in the collecting tubule is blamed for hypertension [167]. The abnormality of a bidirectional sodium-calcium exchanger leads to enlarged calcium entrance into the smooth muscle of the blood vessel in reply to excessive sodium ingestion. The raised calcium entrance leads to vasoconstriction and hypertension as evidence by a study conducted on sodium-sensitive hypertensive rats and transgenic mice [168,169].
The furosemide stress test: current use and future potential
Published in Renal Failure, 2021
Blaithin A. McMahon, Lakhmir S. Chawla
To gain access to the peritubular region, loop diuretics must be secreted across the proximal tubule via binding to the organic anion transporters OAT1 and OAT3 on the basolateral membrane of the thick ascending limb cells. These organic acid secretory sites have an avid affinity for loop diuretics and free the diuretic from albumin. OAT 2 is also expressed on basolateral membrane but has a lower affinity for loop diuretics [13]. States of extreme hypoalbuminemia can interfere with the delivery of diuretic to the proximal tubule and can affect drug efficacy [14]. On the luminal side, multidrug resistance-associated protein 4 (Mrp-4) appears to mediate at least a portion of secretion into the tubular fluid. Knockout mice for OAT1, OAT3, and Mrp-4 are resistant to loop diuretics [15]. Uremic toxins, metabolic acidosis, hypokalemia, NSAIDs and cephalosporin’s all interfere with OAT1 and OAT3-mediated transport of loop diuretics to their site of action [13,16,17].