The overflow switch
(appeared in Mar 2018)

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The body knows how to call for help and to speak up when it has had enough, says S.Ananthanarayanan.

The body knows how to call for help and to speak up when it has had enough

Vineet Augustine, Sertan Kutal Gokce, Sangjun Lee, Bo Wang, Thomas J. Davidson, Frank Reimann, Fiona Gribble, Karl Deisseroth, Carlos Lois and Yuki Oka from the California Institute of Technology, the University of California, Stanford University and the University of Cambridge, in the journal, Nature, describe their study of the mechanism. They find that while the sending the thirst signal has a chemical origin and the surfeit signal has a mechanical origin there is an arrangement by which the second kind of signal suppresses the response to the first!

It is needless to state that the complexity of the processes going on in the body would dwarf that of other systems - man-made chemical factories, computers and machinery, or the interplay of market forces. Most of the processes in the body are chemical and there is need to maintain the necessary conditions, of temperature, saltiness, acidity and the concentration of components, including the available water content. The fluid that surrounds them is called homeostasis.

The human body has a huge number of conditions that have to stay, all the time, within narrow limits. And there is a complex of sensors, control centers and effectors that regulate the levels, which is necessary for the body to function without disease and often to function at all. The regulation is done through organs that act as the sensor of what needs control, the control centre and then the organ that brings about the control. An example of the trio is the mechanism to control the sugar level in the bloodstream. The liver has the marked ability and the function of extracting glucose from the bloodstream or of pouring glucose back into the bloodstream. The liver is thus the effecter.

The liver needs a signal from the control centre to get into action. The signal is the level of insulin in the bloodstream. When there is insulin, the liver absorbs sugar and when the insulin level drops, it puts sugar back into the bloodstream. The control center, which secretes the insulin, is the pancreas and the pancreas acts through cells that sense the level of sugar in the bloodstream.

When the sugar content is at its normal level, there is no secretion of insulin and other cells, liver cells particularly, do not absorb glucose from the bloodstream. And then, when the glucose level drops below normal, the pancreas produces glucagon, which prompts the liver act in reverse, by using its store of energy to created glucose units and glucose alternatives for different cells to use.

Mother substance

While the control of sugar is one example of maintaining homeostasis, there are a great many other substances whose levels and concentration need to be controlled. And the mother substance for most cell processes is water. When the amount of water in the bloodstream falls, the water content of cells diffuses through the cell walls and the water contents of cells gets depleted. This can disable all kinds of body processes and needs to be reversed as soon as possible.

While brain does not have blood flow in the normal sense, there are clusters of cells that are attached to the brain and do have normal blood supply. When the glucose levels drop, these cells detect the change and communicate the condition to the brain. The brain then sends ‘thirst’ signals to different parts of the body, and the person or animal responds by drinking water. The paper in Nature explains that the role of the cells in the brain that receive the signals of levels of the body water content has been verified by artificial stimulation of these regions of the brain in mice, leading to vigorous water drinking.

The question that now arises is, how to the cells attached to the brain, and hence the brain, know that the person or animal has drunk enough water and the sensation of thirst can be turned off? It would take some time, typically a few minutes, for the water that has entered the body to be absorbed and to enter the bloodstream and then the cells. If the sensation of thirst persists, the person would drink too much water, leading to dilution of the bloodstream and the swelling of cells, like prunes soaked in clear water. The cell processes would also be affected by dilution of the cell contents.

The authors of the paper in Nature then studied the factors that inhibit the desire to drink, or the suppression of thirst. Using methods of blanking different brain components and imaging the activity of others, they identified a glucaagon-like main factor that inhibited the action of cells that were first activated when the water content dropped. They found that this factor was acutely activated when the animal started the physical action of drinking – even of lightly salted water or a liquid that was not water. As a control test, it was found that this factor responded when a food deprived mouse licked a source of sucrose solution, but not when it was given solid peanut butter, which was equally nutritious. It was clear that the factor was activated by the physical action of ingesting a fluid and this did not depend on the nature of the fluid. The factor was not activated even if the animal gently sipped real water, the gulping action was necessary. ““These neurons act like fluid flow-meters that tell the brain when the body has had enough to drink. This circuit may be the reason why the brain knows to stop drinking well before the stomach has fully absorbed the all the water an animal has drunk,” says Vineet Augustine, one of the authors of the paper.

The value of the study is that it has revealed a hierarchy in the structure of the brain, which regulates water ingestion by the body. This is important as the regulation of the water content of the body is the issue in a number of diseases, like diabetes, control of the blood pressure, even schizophrenia.

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