Why don’t Humans have a Broader Homeostatic Range?

BY: Abel Tarango-Prieto ChunWoo Kang

April 24, 2010

Introduction

Homeostasis according to the Oxford Medical dictionary is the process by which the internal systems of the body are maintained at an equilibrium despite an external fluctuating environment.

This system of equilibrium allows for very minimal tolerance of range variation in humans compare to ectotherms. With consequences for going above or below set ranges having detrimental effects.

Examples of these conditions that will be later presented are; free radicals, glucose, lipids and iron.

Follow by a look at how ectotherms have an advantage over endotherms/humans by maintaining a broader homeostatic range.

Our interest to investigate why humans posses such a narrow homeostatic range came from what we had learned in our Bio 445 class. Starting with the first example of water intoxication that showed how going over the allowable homeostatic range in either direction, either to much or not enough, can have very serious repercussions. In the case of too much water it can lead to headaches, seizures and something more lethal as cerebral edema.

The question then became why would human adopt a system of control that can have negative impacts even from what can be generally considered essential needs for survival.

Homeostasis is also important to cite is not a system free of charge. It cost energy to maintained and operate. Energy that could be freed if humans had a more broad range of tolerance for homeostatic safe guard.

Hypothesis

If humans could benefit from having a broader range of homeostasis, then reproductive success would show an increase in adaptation of this approach.

We stipulated that due to the many toxic effects that are normally cause by different substances, which are normally non harmful to human physiology, that having a broader range of tolerance to this would be beneficial to the individual. For otherwise it would seem that humans where limiting themselves to much and putting its health on unnecessary harm.

Next would be a presentation of four different substances that normally are essential for normal body function that is until a preset level is cross in either up or down direction is cross.

Free Radical*Definition: Free radicals are molecules-super oxides- produced in living things that uses

oxygen in their respiration. Once the oxygen gas has converted to monoxide, it has to be converted into H2O2 by the SOD, which then gets catalyzed into H2O and O2. However, if the iron takes the electrons instead, the free radical forms.

Are Free Radical Toxin?

*Free radicals are toxin. Due to having an unpaired electron, free radicals are highly reactive. Thus, it goes on and takes electrons from other molecules around and disrupts the regular cellular function. As more cells become dysfunctional due to the free radical over time, it causes humans to be senile.

Effects of Free Radical

*Research conducted by Sacks et al. shows that when the endothelial cells’ Complement-activated PMN in human is damaged, then the cells produce Cr. This then stimulates the granulocytes to produce free radicals that go on to damage endothelium.

[Sacks et al., 1978]

*Research conducted by Harman tries to measure the amount of free radical activity in people by observing the mutation in mitochondrial DNA. Harman shows that in Alzheimer’s disease patients, you observed more mutation in mitochondrial DNA compare to people without the Alzheimer’s disease. This result supports Harman’s idea that the free radical makes the neurons nonfunctional. Thus, with lower free radical activity/formation, we will see less people suffering from Alzheimer’s disease.

[Harman, 1995]

What are we doing about the free radical?

*Many researches are being conducted in order to discover an antioxidant-a strong electron donor that gives off electron to the free radical instead the molecules in our body- humans can take to reduce the damage we receive from the free radicals. For example, Megala and Geetha have conducted a research in vitro using a fruit extract called hydroalcoholic (HAEPD) and tested if it can work as an antioxidant. The results show that HAEPD binds to the free radicals more readily than the molecules from our body’s cells.

[Megala and Geetha, 2010]

*Amarozicz et al. noticed that the pentadienyl free radicals takes away the hydrogen atom from the beta-cerotene, which is essential in producing vitamin A for our body. In order to prevent this activity from occurring, Amarozicz et al. have extracted DPPH+ from green lentil seeds. The results show that DPPH+ binds to the free radicals more readily than the beta-cerotene. Also, the research showed that even though just eating green lentil seeds does help to reduce the free radical activity, it’s not as effective as the extracted purified form of DPPH+.

[Amarozicz et al., 2010]

GLUCOSE

The importance of glucose for the proper function of human life has long been understood. It’s role in participation in the energy cycle is of great

importance .

The importance of glucose can not be ignore for it is found in almost everything that we consume. Been such a major part of our daily diets

it effects in our metabolism have to be taken seriously.

Specially in this country where a combination of increase consumption of highly process foods high in sugars and decrease in physical activity,

according to the Center for Disease Control (CDC), keep pushing the levels out of the normal ranges for physiological optimum performance.

Glucose overview

Glucose regulation is maintained via negative feed mechanism.

1. When glucose enters the blood system after ingestion an increase in blood sugar stimulates the release of insulin from the pancreas. Insulin in return works to stimulate formation of glycogen which is then stored in different tissues, eg. Muscle.

2. When sugar blood leves become low glucagon is then release by the pancreas stimulated the breakdown of glycogen release glucose to be use by the body.

Glucose Range Normal ranges of glucose: at

fasting is 80 to 90 milligrams per deciliter, after a meal it can go to around 120 milligrams per deciliter.

As it can be seen in the figure to the left the range for people with prediabetic inclinations and those that are diabetic have ranges that are a less narrow. It shows how the begins to develop what is called impaired glucose toleranse.

(Beaser, et al. 1995)

Glucose Toxicity

Chronic exposure to high levels of blood glucose, hyperglycemia, over the period of many years leads to adverse changes in special to beta cells that became defective or died as of consequence, severely affecting insulin secretion, reaching high levels above 180 to 200 mg/dL it starts to spill glucose into the urine damaging kidneys, as it continues to get higher it will also begin to affect the eyes, blood vessels and nerves. (Giaccari et al. 2009 and Robertson et al 2006).

When sugar falls below its normal range of 60 mg/dL that is called hypoglacemia, with some of its toxic symptoms been shakiness, hunger, and racing of the heart. When it drops lower than 50 to 40 or less then loss of mental function, unconsciousness, and seizures can result.

Lipid*Definition: Lipids are composed of fats, steroids, and fat soluble vitamins. They stores the

most amount of energy in our body and maintain our body temperature. Lipids are also called triglyceride, which is from with one glycerol with three fatty acids. Based on the formation of the fatty chain, either the triglyceride is formed with mixture of double bonds and single bonds, or only formed with single bonds, the lipid can be a low-density lipoprotein or high-density lipoprotein.

Are Lipid Toxin?

*Lipids are toxin if we have too much. The amount of lipid, in general, has a positive correlation with the cholesterol level. Thus, if people are obese, which can be measured using the Body Mass Index (BMI), they tend to have a higher cholesterol level. High cholesterol level-above 200mg/dl- has been know to cause diabetes and hypothyroidism .

Effects of Lipid

*Chow et al. conducted a research on the effect of lipids on the Andhra Pradesh Indians. Chow et al. measured the lipid levels along with the cholesterol levels in 4535 individuals throughout the 20 villages. The results show that people who have been determined to be obese and were over the age 30 showed significant increase in cardiovascular problems.

[Chow et al., 2008]

*Gordon et al. have compared a women who are diabetic, women who have low high-density lipoprotein cholesterol level, and an obese women. This was done to show the which will lead to more coronary heart disease. The results show that the obese women had the highest risk for coronary heart disease and women with low high-density lipoprotein cholesterol level showed lowest risk for coronary heart disease. The reason for this has been found to be due to the amount of triglyceride present in the blood stream. The study shows that with more triglyceride present in your blood stream, more likelihood of suffering from a coronary heart disease in the future.

[Gordon et al., 1977]

What are we doing about the lipid and its associated obesity?

*Artham et al. conducted a study to show the benefit of exercising. Artham et al. collected data from exercise training programs and measured the plasma lipid level along with the obesity. The results show that people who regularly exercise showed a much lower plasma lipid level and less obese compare to people who did not exercise regularly. Thus, people who exercise regularly has a less risk of coronary heart disease.

[Artham et al., 2008]

*Dattilo and Kris-Etherton has conducted a research to compare the metabolic rate for a low density lipoprotein cholesterol verses high density lipoprotein diet. They analyzed 70 people, 35 on low density lipoprotein cholesterol diet and other 35 on high density lipoprotein diet, and found that people metabolized the high density lipoprotein diet metabolizes quickly so it doesn’t linger and built up a plaque in the artery like the low density lipoprotein diet.

[Dattilo and Kris-Etherton, 1992]

Iron

A very abundant basic element that it is a central atom in Hemoglobin that binds with Oxygen.

Because of Iron four molecules, four Oxygen can bind to one Hemoglobin.

There are approximately 280 million molecules of hemoglobin in each red blood cell and each red blood cell can carry over 1 billion molecules of Oxygen.

But that is not the only function of Iron, it is also plays a part in brain neurotransmitter production, as well as production of connective tissue.

Iron Regulation

Iron homeostasis is controlled both at the system and cell level. With Hepcidin playing a key role as regulator at the systemic level and Proteins IRP1 and IRP2 at the intracellular level. Starting with absorption at the small intestine (duodenum) hepcidin modulates transferring transferring by inhibing FPN (the principal or only cell iron exporter). Hepcidin synthesis takes place in the liver and it’s normally regulated in two ways; first positively by body iron stores and secondly by erythropoietic activity and hypoxia. (Recalcati et al. 2009)

Iron Range

Normal readings for Iron levels are as follow; Adult males: 75-175 micrograms/dL Adult females: 65-165 micrograms/dL

Children: 50-120 micrograms/dL Newborns: 100-250 micrograms/dL.

In the box to the right there is a U.S Department Agriculture recommended %DV responding to the age and sex of individuals.

It is important to note that because of the Iron is found in a lot of the things we normally consume specially in red meats, ready-to-eat cereals and oatmeal which most are 100% fortify with iron, beans, many varieties of fish products and some vegetables such spinach. Adding to this the fact that in a good number of people in America also take vitamin supplements that also can contribute to the levels of iron already present, one has to be particular concern with it possible toxic effects.

Iron Toxicity Going over the homeostatic range for allowable iron will cause a condition

called hemochromatosis. Which would can lead to skin pigmentation changes, hepatic and cardiac complications, skeletomusucular damage and compromise of immune system. Specially lethal among patients with sickle cell diesase.

Of special interest here are those that sufer from hereditary hemochromatosis (a homozygous condition) where excessive iron is absorbed from the gut, about 2 to 3 times the normal quantities. Heterozygotes are still carries that even do might be asympomatic still remain carriers. Of those suffering from this one point mutation don’t show any symptoms until age 20, which if not treated can cause increase risk of cardiac disease and possibly early death. (Ponka, 2002)

Low plasma iron, anemia, leads to a decrease of total iron-binding capacity, decreases bone marrow sideroblast, imparing erythropoietin production. Also something new the has began to be study in primates is disruption in normal fetal brain development due to anemia. (Price et al 2010 and Golub, 2010)

Ectotherm vs. Endotherm*Ectotherms are animals(Salamanders, all reptiles, and lizards) that obtain their energy/heat

from their external environment, such as conduction, infra radiation, and convection. They are much more efficient in converting the energy/heat from one form to another than the endotherms. Thus, they have the ability to live in more extreme environments. For example, marine iguanas can live on land in moderate temperature like humans, but they can also swim for hours in the cold sea water unlike humans. This broader homeostatic range in the marine iguana/ectotherm is possible because they can efficiently convert the energy they get from their external environment.

*Endotherms are animals(Passerine birds, and placental mammals-such as human) that obtain their energy/heat by metabolizing the food they eat. They use over 50% of the energy they obtain just in generating the heat they need to survive, so their energy efficiency is low. Because of their inefficient way of converting their energy, they can’t live in two extreme environments. For example, humans/endotherm can’t stay long in the sea like the marine iguana/ectotherm since humans can’t convert their energy into heat efficiently. This shows the narrow homeostatic range endotherms have compare to ectotherms.

Discussion

*As you have seen from the comparision between ectotherms and endotherms, having a broad range of homeostasis looks to be more beneficial. Some ectotherms use the energy they have obtained from their environment efficiently so they can live in extreme environments. If humans were ectotherms then we have all the extra energy to spend in other places. For example, in order to obtain antioxidants to develop tolerance for free radicals produced in our body, we need to eat five to eight servings of fruits per day. This may not sound like much now; however, in our evolutionary past, getting even that amount of fruits and vegetables was not easy. If humans were ectotherms, we can use more energy in obtaining more antioxidants from the fruits we eat since we don’t have to waste the extra energy on producing body heat. Also, because we are so efficient in converting energy, our body won’t need to store as much lipid to maintain our body temperature. We will get most of the temperature we need from our external environment. Thus, we could potentially avoid all the unwanted effects from the toxins like free radicals and lipids and survive better. Since increased survival rate would increase one’s reproductive success, why didn’t the Natural Selection favored broader range of homeostasis and direct humans to evolve into ectotherms?

Discussion cont.

The other two examples of glucose and Iron have also shown us that there has been no selection for a broader range of tolerance. With glucose having negative effects when ever its levels where either above, hyperglacemia, or below, hypoglacemia. Negative impacts also present when Iron fail to stay with in an allowable range of tolerance too much and we had hemachromatosis, and when below the normal range anemia. While maintaining these narrow ranges seems at first hand to have adverse effects in the reproductive success of humans for it would looks like the body is limiting itself it actually not the case. It is by keeping a homeostatic balance that has allow humans to be able to adapt to many different environment’s while at the same time maintaining a highly conserved internal environment. This is of great importance because by keep and internal environment it has allowed cells to become more specialized and efficient at whatever their particular task might happened to be. Of course the disadvantage as it was demonstrated in the above examples is that when these controls of homeostatic regulations fail to act or break down it will give rise to illnesses, putting the individual at risk.

Conclusion

*Even though it seems that Natural Selection would prefer broad range of homeostasis, it didn’t grant humans with a broad range of homeostasis compare to ectotherms.

*Why would this be the case? -This is because “THERE IS NO FREE LUNCH”.

*It is true that ectotherms have broader range of homeostasis than us humans who are endotherms. However, even though humans/endotherms have narrower range of homeostasis, they have other advantages for being an endotherm. By giving up a broader range of homeostasis, humans/endotherms have acquired an ability to move around freely at their full metabolic rate during night, early in the morning, and in cloudy days when there’s no sun to provide the energy. This benefit that follows from giving up the broader range of homeostasis may have had higher reproductive success in certain animals, such as humans, to become an endotherm.

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