Sodium is the major extracellular cation, and its concentration is tightly to ensure physiologic functioning.
While guidelines recommend less than 2.5 g of sodium daily, average intake in the West ranges from 2-10g (check this).
Amounts of water in the body is directly propotional to sodium levels, and weight gain or loss accompanies changes in sodium intake to maintain homeostatic concentrations. Abrupt changes in sodium intake will create a period of positive or negative sodium balance as the kidney takes 12-24 h to adjust levels of sodium excretion to match intake.
Sodium absorption largely occurs in the colon, where it passes through aldosterone-regulated channels. Sodium's concentration gradient is used for the absorption of monosaccharides and amino acids via co-transporters in the gut, primarily in the jejeunum. Each of these mechanisms is dependent on Na/K ATPase function.
Sodium can also be absorbed paracellularly, and as is the case for water, this is most effective in the duodenum due to its 'looser' tight junctions.
Normal plasma sodium concentration is 137-145 mmol/L.
Sodium is freely filtered in the kidney glomerulus, leaving filtrate concentration similar to that of blood. The 180 L of blood filtered daily through the kidney contain almost 2kg (25.5 Mol) of sodium, and with 2-10g taken in daily, the vast majority of it (25.4 Mol) must be reabsorbed. About 5% of salt intake is lost through sweat or through feces.
A huge amount of this occurs in the proximal tubule and loop of Henle, and the remaining amount is under precise regulation in the distal tubules and collecting ducts to maintain salt balance.
Sodium leaves the tubule lumen via electromotive and osmotic forces along its gradient, but is pumped out against its gradient into the interstitium via the Na/K ATPase. It then passes freely into the blood to complete reabsorption. The kidney uses 7-10% of the body's oxygen demands, even though they account for less than 0.5% of total body weight. This is in parge part due to activity of the Na/K ATPase and its role in Na+ reabsorption.
Site |
Mechanism |
% |
Inhibitor |
Stimulator |
|---|---|---|---|---|
proximal |
Na/H exchanger, Na-X symporter |
65 |
||
thick ascending loop |
Na/K/Cl2 triporter |
25 |
||
distal |
Na/Cl symporter |
5 |
||
collecting duct |
ENaC channels in principal cells |
2-5 |
In the proximal tubule, the sodium gradient drives co-transport of bicarbonate, amino acids, glucose, and other organic molecules.
Regulation of GFR increases or decreases the amount of sodium passing through the tubules. NaCl concentration is sensed in the macula densa of the kidney, with low levels of NaCl causing renin release.
Increased plasma osmolarity signals increased thirst and ADH secretion in order to increase plasma volume. Interestingly, it also increases salt appetite.
ADH is primarily involved with reguation of water retention. It also increases sodium channels in the TAL, increasing plasma osmolarity in order to draw water in. Volume takes precedent over free water.
Increased flow leads to elevated GFR. An increased filtration fraction decreases hydrostatic pressure in the peritubular capillaries, increasing the driving force from the interstitium to the capillaries and thereby increasing absorption of fluid and NaCl.
Sympathetic innervation has three major functions:
Ang II, activated by renin secretion:
Aldosterone increases Na channels, Na/K pumps, and ATP production in the principal cells of the distal tubule and collecting duct, increasing Na resorption. Aldoserone's effects primarily occur in the kidney, but it also works on sweat glands and the colon to increase sodium reabsorption.
ANP binds to prinicpal cells and activates guanylyl cyclase, which produces cGMP that inhibits ENaC channels. ANP also inhibits aldosterone release and renin production, increasing GFR by dilating afferent arterioles. The net effect is to increase sodium excretion.
Prostaglandins and Bradykinin are produced locally in the kidney and inhibit sodium reabsorption.
Dopamine is produced in the kidney from circulating L-dopa and causes renal vasodilation, leading to increased Na excretion. It also directly inhibits Na reabsorption.
Sodium is reabsorbed via the epithelial Na+ channel (ENaC) at the lumen and transported basolaterally by the Na/K ATPase. The hormones aldosterone and ADH both increase Na+ resorption, while prostaglandins, ANP, and nitric oxide reduce it.