** Osmoregulation and Intercranial Pressure

” Regulation of the cerebral circulation relies on the complex interplay between cardiovascular, respiratory, and neural physiology. In health, these physiologic systems act to maintain an adequate cerebral blood flow [CBF] through the modulation of hydrodynamic parameters; the resistance of cerebral vessels, and the arterial, intracranial, and venous pressures. In critical illness, however, one or more of these parameters can be compromised, raising the possibility of disturbed CBF regulation and its pathophysiologic sequelae.” Crit. Care 2016 May 5;20(1):129. doi: 10.1186/s13054-016-1293-6. Regulation of the cerebral circulation: bedside assessment and clinical implications Joseph Donnelly 1Karol P Budohoski 1Peter Smielewski 1Marek Czosnyka 2 3

In physiologybody water is the water content of an animal body that is contained in the tissues, the blood, the bones and elsewhere. The percentages of body water contained in various fluid compartments add up to total body water (TBW). This water makes up a significant fraction of the human body, both by weight and by volume. Ensuring the right amount of body water is part of fluid balance, an aspect of homeostasis.

Body water changes with age. It is an important component to consider when evaluating mental status .especially during major hormonal and developmental physical changes of development and growth.

 Up to 60% of the human adult body is water. According to H.H. Mitchell, Journal of Biological Chemistry 158, the brain and heart are composed of 73% water, and the lungs are about 83% water. The skin contains 64% water, muscles and kidneys are 79%, and even the bones are watery: 31%. https://www.usgs.gov/special-topic/water-science-school/science/water-you-water-and-human-body?qt-science_center_objects=0#qt-science_center_objects

The brain is incased in bone. Maintaining water and salt balance [osmoregulation] in bodily fluids is a dynamic ongoing process. Osmoregulation must be trickier to regulate in the head and in the spinal column. Bone is rigid. It is likely that if one experiences a sudden change in mental ability and in locomotor activity, that the problem may involve water and salt [solute] balance disturbances pushing on and affecting the brain and the spinal cord. Our futuristic biological clinic for disturbances in mind, mood, and motor function would gather clues by measuring physical functioning to explore the hypothesis of homeostatic failure to some part of the system explaining the changes in mental function. Changes in sodium and water balance have a profound effect on the brain and central nervous system (CNS) 

Osmoreceptors, located in the hypothalamus (and also in the carotid artery) are capable of sensing the concentrations of solutes, particularly sodium ion. This leads to a secretion of vasopressin. Vasopressin regulates the  tonicity of body fluids. It is released from the posterior pituitary in response to hypertonicity and causes the kidneys to reabsorb solute-free water and return it to the circulation from the tubules of the nephron, thus returning the tonicity of the body fluids toward normal. Vasopressin selectively raises free water reabsorption through the upregulation of aquaporin-2 water channels in the collecting duct, resulting in blood pressure elevation An incidental consequence of this renal reabsorption of water is concentrated urine and reduced urine volume.(Elliot et al., 1996; Linshaw 2011).
Vasopressin – an overview | ScienceDirect Topicshttps://www.sciencedirect.com › medicine-and-dentistry

No one in the 21st century really understands how the brain regulates osmosis given the wide range of interaction between food, drink and internal bodily processes. How Does the Brain Sense Osmolality? Joseph G. VerbalisJASN December 2007,  18 (12) 3056-3059; DOI: https://doi.org/10.1681/ASN.2007070825

In the 22nd century, people know that careful assessment of hydration status, looking for possible evidence of oedema, dehydration and poor general body condition, as well as vital signs help to evaluate the process of homeostasis. This evaluation takes time in order to understand what is going on in the body and how the brain is being affected. It involves collecting physical clues and figuring out what we are unable to see but able to puzzle out, by looking to see if any homeostatic feedback mechanisms are impaired……….

Kraepelin’s studies are useful to the scientists of the 22nd century because medications were not available then and so he was able to establish the signs and symptoms of bipolar patients in different stages of illness as they got sicker.

Kraepelin could easily see poor body condition and dehydration and weight loss in his depressed bipolar patients with altered mental status. And he taught others on staff to do the same. Measurement and observation of the patient was key. Dehydration should result in lower blood pressure. Kraepelin found very high blood pressure in these patients.

Kraepelin’s results were similar to those we saw in Paula during her depressive episode. In the 22nd century clinic, her loss of appetite, loss of thirst and loss of weight would be noted as her physical condition worsened. She seemed not to urinate or defecate [not many trips to the bathroom] and in 3 weeks she looked poorly, although she did not look as poorly as the patients Kraepelin described in in his descriptions of body condition in depression.

” In states of depression, …the skin becomes pale, wrinkled, withered, dry, rough; the eye becomes dull the growth of nails stops and becomes irregular, the menses become scant or intermittent ; the secretion of tears dries up; the whole being appears prematurely old. “ Emile Kraepelin Manic Depressive Insanity, 1926.

In hypomanic periods, the skin acquires a fresh color and tension; the movements become elastic and vigorous,; the scanty hair grows afresh, even with renewed colour.

All these changes indicate that in manic depressive insanity, marked disorders of metabolism must take place”. page 48, Emile Kraepelin Manic Depressive Insanity, 1926.

The clinic of the 22nd century was looking at the vital signs of patients like Paula. They did not find low blood pressure that usually accompanies dehydration and volume contraction. Instead they found extremely high blood pressure , same as Kraepelin did. . They also found palpitations, arrhythmia’s and heart murmurs.

Verify this: And they found abnormal breathing, in Paula’s case, they found hypoventilation [a low minute volume with normal lungs but a depressed breathing rate.] Intracranial hypertension can cause changes to breathing drive and effort. These changes are seen in both the depressive and manic stages of this syndrome and have got to be significant.

Could Paula’s bipolar depressive attack be due to increasing hypercapnia? . Hypercapnia triggers vasodilation, which leads to an increase in cerebral blood volume [CBV ] and a subsequent increase in intracranial pressure [ ICP]. This results in blood pressure being raised in order to maintain failing cerebral perfusion which accompanies intracranial hypertension.

What if the depression and the inhibition of normal mental function was a result of growing pressure inside the head from the failure of motor control of breathing ? Activation of the sympathetic nervous system due to an internal emergency should result in faster breathing yet Paula’s breathing was still depressed. Even in the 22nd century, they were struggling to understand what was happening. What is becoming clear though, is that the main stressor in bipolar attacks seems to involve motor impairment of the ventilatory system underlying breathing. The lungs are fine. As a result, the function of the brain and the mind is altered when pressure begins to increase in a rigid skull.

Not eating or drinking will stop growth, and will reduce body water and this will also slow down accumulation of pressure in the head. Not moving much helps lower body temperature and this too keeps pressure in the head in check.

 A classic triad of bradycardia, respiratory depression, and hypertension is known as Cushing’s triad and is highly indicative of intracranial hypertension. Two out of three is what Paula had during her attack of bipolar depression. She did have a bunch of heart disturbances but not bradycardia, to the best of our knowledge.

Bradycardia was more likely to occur in mania, oddly enough, with hypertension [not as high as in the depressed state] and irregular respirations. Again, indicative of intracranial hypertension. This was what Jerry presented at the height of his illness.

Careful monitoring of vital signs and respiratory rate and depth are key to understanding the hormonal responses of bipolar depressive and manic episodes.

This is why altered mental status and mood and locomotor activity are indicative of critical illness which, even if it does not immediately kill you, will certainly prevent you from leading a normal life.

to be continued….

To investigate changes in mental function, simple basic tests of reading, comprehension, arithmetic were given to patients, tests that any grade school child could do. The simple basic tests were timed to look for speed of mental function. It was easy to get an idea of normal performance by doing the test yourself to get an idea of disturbed or altered function in someone else, [hence pointing to “altered mental status”].

There are many ways to test whether mental status is altered or not. Asking a family member to quietly accompany and quietly assess the person’s ability to conduct their daily activities is another. Can they perform as they did before they got ill. Do they remember to shower, can they dress themselves and look appropriate ,have they put on different coloured socks, do they forget to brush the back of their hair, as they would usually [if they did usually], can they perform their job, can they interact in their usually way with others. In short, evaluating mental status will require having a person do something to evaluate if they can still do it A simple basic timed test asking a person to do grade 6 level work will do . Or simple observation of the person to see if they can maintain their usual level of function. [preferably by someone who knows their usually level of functioning.].

In the 22nd century the Biological Clinic investigating mental disturbance would give inexpensive, basic training to learn to correctly measure all the vital signs at rest when awake. At rest, the vital signs will be easy to study, will be reproducible, and will react in predictable patterns to disturbances in osmoregulation, especially as it affects the brain, mood, mind and locomotor activity rate and speed in spontaneously behaving people.

This is hy the 22nd century developed the biological clinic for the study of mental disturbances.

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