Kidneys control the fluid, potassium, and sodium balance in our bodies. This balance is the major determinant of blood pressure. The kidneys seem to allow a large intake of potassium, and they do an excellent job of conserving large amounts of sodium. Evolution probably explains why this occurs. Thousands of years ago potassium was easy to get in food and sodium was hard to get. Food was mostly alkaline. But the question remains of how the kidneys do this. The Yanomami provide the clues.
Scientists have discovered many potassium channels, sodium channels, active pumps, and proteins called co-transporters in our cells to balance sodium and potassium. They come in a variety of forms, and use differing mechanisms to perform their balancing work.
One Balancing Method Kidneys Use
One of the best known methods of balancing potassium and sodium involves an exchange of potassium and sodium in the distal part of the kidney in the principal cells (PC) of the connecting tubule. These kidney cells are located between blood vessels and tubules that carry urine to the bladder.
The principal cells (PC) have channels, pumps, and co-transporters that move potassium, sodium and other ions around. Two channels in the PC are located on the cell surface that lines the tubule that carries urine eventually to the bladder. The Epithelial Sodium Channel (ENaC) lets sodium into the cell from the urine and the Renal Outer Medullary Potassium channel (ROMK) lets potassium out of the cell into the urine.
On the cell surface that is against blood vessels, the sodium-potassium-ATPase pump (Na-K-pump) gets energy from ATP to move sodium out of the cell into the bloodstream and potassium into the cell from the bloodstream. It needs energy to do this since the natural tendency is for potassium to move out of the cell and sodium into the cell. It can do this through the two channels, ENaC and ROMK.
So the overall process would be as follows. The pump pushes sodium out of the cell into the bloodstream. This creates a lack of sodium inside the cell, so sodium leaves the urine to enter the cell through the ENaC on the opposite side of the cell. The pump pulls in potassium from the blood stream which creates too much potassium in the cell. So potassium leaves the cell to enter the urine through the ROMK channel. This is how the cell can keep the right number of potassium and sodium molecules inside the cell.
Limitation Of This Method
One problem with this mechanism is that the ratio of potassium excreted to sodium absorbed from the urine is limited. Because the Na-K-pump exchanges 2 potassium for 3 sodium, the best ratio that this pump can achieve in the urine is 0.67. This would be a big problem for early animals, including mankind. The food that was available had lots of potassium and little sodium. For most food the ratio of potassium to sodium was 7 to 1 up to 50 to 1. So the food that was eaten and absorbed into the bloodstream would overload the bloodstream with potassium and starve the bloodstream of sodium.
Another method to balance potassium and sodium was needed. Studies in the 1960s and 1970s of the blood pressure of indigenous peoples gave some clues. Some of the best clues came from studies of the Yanomami. They provided a lot of clues. Yanomami can get a much higher ratio of potassium out than allowed by this pump mechanism. In the report from 1975 (1), they had a ratio of potassium to sodium excreted in the urine of over 150 to 1. The North American controls in that study had a ratio of less than 0.4. So there must be another way to get rid of so much potassium. The question is how the Yanomami do it. To do it, the potassium secretion would have to be independent of the ENaC-sodium pump that we just mentioned, since it has such limited potassium excretion and sodium reabsorption.
The 1975 paper gives a clue about how the Yanomami do it. It showed the Yanomami excrete only 10% of the amount of chloride that the North American controls do. This would indicate a much more alkaline urine than the North Americans had. The Yanomami had to excrete some other anion besides chloride. The most abundant anions in their diet were bicarbonate and bicarbonate precursors, because of the alkalinity of their diet. So bicarbonate became the primary suspect for the authors of the study (2) to be discussed.
Another curious finding in the 1975 study is the huge increase in aldosterone and renin in the Yanomami. Their blood levels were 10 times the levels of the North American controls. Levels that high in the North Americans would indicate hypertension, but the Yanomami had no hypertension.
Renin is understandable since the blood pressure is low and there is so little sodium in the urine. Aldosterone could also be increased somewhat from this. But 10 fold? Could it be that the Yanomami have normal aldosterone and renin levels, but modern humans have abnormally suppressed levels from the poor potassium sodium ratio of our diet?
Aldosterone should help increase the amount of potassium excreted. Aldosterone has been shown to increase sodium-potassium-ATPase, ENaC, and ROMK and thus increase the amount of potassium secreted into the urine. But the ratio of potassium excreted to sodium reabsorbed is still limited to a ratio of 0.67, the exchange ratio of sodium-potassium-ATPase pump. So once again, we have an indication that the kidney must have another way to get rid of potassium and hold onto sodium.
How The Kidneys Do It
The researchers (2) looked at how another cell besides the PC, the intercalated cell (IC), might allow more potassium to be excreted and how an alkali, such as bicarbonate, might contribute to increased potassium excretion. They previously had found a great many BK channels in the intercalated cells.
The BK channel is an important potassium channel. In the kidney, most of these BK channels are in the intercalated cells (IC). But these cells have very little sodium-potassium-ATPase. If they are pushing out potassium into the urine, where do they get the energy to do so?
The IC have a different way to use ATP for energy. Intercalated cells mostly transport acid and base. The IC have much more H-ATPase (proton pump) than sodium-potassium-ATPase (Na-K-pump). Since these cells are involved in acid base balance and sit next to the PC, might the IC and PC work together in some manner?
The researchers found that these cells do work together. The researchers found that when there is little sodium and little chloride, and lots of potassium and lots of bicarbonate, the IC and PC can work together to recycle sodium and chloride by getting rid of potassium and bicarbonate. In the IC, chloride gets reabsorbed from and bicarbonate gets excreted into the tubule.
There are two mechanisms for getting rid of the bicarbonate and reabsorbing chloride. One mechanism uses pendrin. Pendrin sits on the tubular side of the cell and pushes out bicarbonate in exchange for chloride, independent from sodium. The second mechanism uses an exchange of bicarbonate for chloride performed by a co-transporter known as the Sodium Dependent Cl-Bicarbonate Exchanger (NDCBE). It requires a sodium to also be excreted into the urine in addition to the bicarbonate-chloride exchange.
Sodium that gets excreted, though, can be reabsorbed by the PC. The PC then drives sodium into the bloodstream with the sodium pump. The sodium then gets recycled into the IC from the bloodstream by the Sodium-Potassium-2Chloride co-transporter 1 (NKCC1).
This recycling of sodium and chloride is driven by the H-ATPase (proton pump) in the IC. It provides the energy needed without the 0.67 limit of the Na-K-ATPase pump. It allows a large amount of potassium to be passively excreted by the abundant BK channels in the IC, and a large amount of bicarbonate to be excreted by the NDCBE co-transporter and pendrin.
The study validates the epidemiological and experimental human group studies showing the importance of a diet of foods with a high ratio of potassium to sodium with alkaline bicarbonate precursors, that is, high potassium foods. But it also shows how, when the kidneys are not functioning well, this mechanism may not work. It partly explains how kidney failure is related to high blood pressure. And it shows how the high potassium foods diet could be unsafe for those with poor kidney function or whenever this mechanism is unavailable.
What The Study Means To You
But what does this study mean to you? It means that if you are healthy you can eat foods that have lots of potassium, and bicarbonate precursors like citrate. Your body has you covered. It means that you can eat foods with little sodium or chloride. Your body knows how to recycle them. When you do eat this way, you will be eating like the Yanomami who have no hypertension.
1. Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Oliver WJ, Cohen EL, Neel JV. Circulation. 1975 Jul;52(1):146-51.
2. Relation between BK-a/ß4-mediated potassium secretion and ENaC-mediated sodium reabsorption. Wen D, Cornelius RJ, Rivero-Hernandez D, Yuan Y, Li H, Weinstein AM, Sansom SC. Kidney Int. 2014 Jul;86(1):139-45. doi: 10.1038/ki.2014.14. Epub 2014 Feb 26.