The Arg83Gly SNP specifically results in a large reduction in the flow of chloride ions through the ClC-Ka channel in the thin and thick ascending limb of the nephrons.
22.
In the kidneys, elimination of potassium is passive ( through the glomeruli ), and reabsorption is active in the proximal tubule and the ascending limb of the loop of Henle.
23.
Also, the medullary interstitium is highly concentrated ( because of the activity of the ascending limb ), leading to a strong osmotic gradient from the descending limb to the medulla.
24.
The Na + / K + / 2Cl " transporter in the ascending limb of the loop of Henle helps to create a gradient by shifting Na + into the medullary interstitium.
25.
For example, the large majority of passive transport of water occurs in the proximal tubule and the descending thin limb, or the active transport of NaCl largely occurs in the proximal tubule and the thick ascending limb.
26.
It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla as the descending limb, and then returns to the cortex as the ascending limb to empty into the distal convoluted tubule.
27.
Loss of function of this reabsorption system results in decreased sodium, potassium, and chloride reabsorption in the thick ascending limb, as well as abolishment of the lumen-positive voltage, resulting in decreased calcium and magnesium reabsorption.
28.
Proper function of all of these transporters is necessary for normal ion reabsorption along the thick ascending limb, and loss of any component can result in functional inactivation of the system as a whole and lead to the presentation of Bartter syndrome.
29.
The Differentiator Model proposes that individuals at greatest risk for developing alcohol use disorder ( or those who already meet criteria for alcohol use disorder ) are more sensitive to the stimulating effects of alcohol on the ascending limb of intoxication and less sensitive to the sedative effects on the descending limb.
30.
However, Bartter syndrome is also characterized by high renin, high aldosterone, hypercalciuria, and an abnormal Na +-K +-2Cl " transporter in the thick ascending limb of the loop of Henle, Gitelman syndrome causes hypocalciuria and is due to an abnormal thiazide transporter in the distal segment.
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