In the scientific study of human physiology, the goal of which is to understand the functioning of the body, it is integral to understand the tendency of the body to drive it self towards homeostasis. Human physiology requires an understanding of the mechanisms that work at the cellular level which in turn drive the organs and organ systems. In simple words, homeostasis is the state of steady internal conditions maintained by living organisms. It is derived from the two roots- “homeo” meaning similar, and “stasis” meaning stable.
The environment, can cause changes in the internal physiology of the body. This makes homeostatic regulation a central feature of bodily maintenance so that optimal functioning can be established even in the presence of adverse condition. For instance: excessive exercising causes the body to heat up. This sensation travels to the temperature regulatory center in the brain (part of the hypothalamus), through the nerves. The brain signals the sweat glands to open up. In order to maintain the human temperature, the body sweats. Evaporation of sweat from the body surface, causes it to cool down. This is a way through which the body brings back its temperature to normal.
Maintenance of optimal water levels in the blood is a key aspect of optimal bodily functioning. Drinking less water (a condition of dehydration) causes the water levels in the blood to fall. This can again be detected by the hypothalamus. Upon detection of low water levels in the body, the hypothalamus signals the pituitary gland to release excessive antidiuretic hormone (ADH). ADH acts in a paracrine manner and signals the kidneys to excrete less amount of water in urine and return more water into the bloodstream. Urine colour changes to yellow as a result of less water component. This way the homeostatic level of water, in the bloodstream can be reached again. The opposite occurs when the human body intakes too much water. In this case the hypothalamus signals the pituitary glands to decrease the release of ADH. The kidneys, as a result of detecting less ADH, excrete more water into urine. Thus, establishing the steady state again.
Homeostatic regulation requires lot of communication between the cells of the body. Paracrine (cells release signals that affect nearby cells) and autocrine factors (cells release signals that cause changes in the cell itself) mediate local control. The other, more systemic form of control is reflex control, that involves the endocrine and the nervous system. It involves the participation of the sensor cells, detector cells, the integration center (usually the brain), and the effector cells. The nervous system and the endocrine system play an important role in this. The main mechanisms of reflex control are discussed below-
Negative feedback loop: this act to reverse the direction of change of the causative stimuli. The example discussed earlier on maintaining water levels in the blood via ADH is an example of a negative feedback loop.
Feed- forward loop: the stimuli results in the increase in the rate of change in the direction of the response. For example: suckling by the baby, results in production of more prolactin by the pituitary gland, resulting in more lactation.
Tonic control: nervous control, maintains a normal level of activity in the effector organs. They are usually slow and graded in nature. The sympathetic and parasympathetic nervous system have several targets in the cardiovascular system that control hemodynamics and blood pressure.
Antagonistic control: opposing factors counterbalance each other’s effects in order to maintain optimal levels in the body. For instance: insulin signals the body to take up glucose from the blood and store it as glycogen. Glucagon is released as a result of lower blood glucose levels. It triggers the cells in the body to convert the stored glycogen into glucose and release it back into the blood stream.
The main regulatory systems that the body needs are - osmoregulation, thermoregulation, and chemical regulation.
The human body can be divided into two compartments- intracellular fluid and extracellular fluid. The intracellular fluid (ICF) is the compartment inside the cell membrane- i.e. the cytoplasm. The extracellular fluid (ECF) lies outside and acts as a buffer. Flow of ions and other small soluble compounds take place through the cellular membrane between the ECF and ICF. The ECF undergoes changes due to external factors and its osmolarity is maintained by flow of water and solute particles through the plasma membrane. For instance: if the ECF has excess levels of water then water will flow into the cell (ICF).
Several chemical reactions take place in the body in order to maintain homeostasis. An example is calcium homeostasis. Excess calcium in the blood, is stored in the bones. Calcium exists as a cation in the blood and as calcium hydroxyapatite in the bones. The interconversion of the phosphate bound state to the free cation state is a chemical reaction.
Lastly, thermoregulatory mechanisms involve cellular respiration to produce heat in the body and mechanisms such as sweating as mentioned earlier.
Recent studies have proposed three models to explain body weight homeostasis. Body weight is believed to be under the control energy mechanisms, fat storage mechanisms, and genetic and environmental factors. The first model proposes a “set point” for body weight. Overfeeding mice, resulted in disproportionate weight gain. However, diet restriction after this, resulted in the mice regaining its original weight. This suggests that there is a genetic control over the set point of the body weight. Leptin is a hormone that regulates energy balance in the body. Its release is controlled by the hypothalamus which is in turn sensitive to the adiposity of the body. A modification suggests that “the anabolic response to leptin becomes evident only when plasma leptin levels have fallen under a certain threshold level, which may resemble a low set point related to starvation and the risk of death.”  This is asymmetric because there is no biological control associated with overfeeding.
A second model proposes that, over- feeding and under- feeding leads to changes in the “difference” between energy intake and expenditure. Changes in this difference causes the body to “settle” for a new intermediate steady state body weight. There exists a third model to explain body weight and it combines the above two models. It proposes that there exist two set points (upper limit and lower limit) to the body weight and a settling point in between. This allows incorporation of the genetic control as well as modulation in the leptin feedback cycle due to environmental factors. More experiments still need to be done in order to verify these theories on body weight homeostasis.
There have also been advances in the understanding of the role of gut microbiota in maintaining a steady state in the gastrointestinal system. The microbial flora differs from person to person and vary in healthy and diseased persons. The microbiome cross-talks with the mucosal immune system and also the digestive signals. They play a crucial role in mediating tolerance to certain opportunistic pathogens. They also act upon ingested antibiotics and can potentially mediate drug efficacy or resistance. Shotgun analysis is being used to analyze the phylogenetic make-up of the microbiota in different people. It has been suggested that use of probiotics can be very helpful in warding off bacterial infection and re-establishing homeostasis. Probiotics are live microorganisms derived from the human gut that have beneficiary effects on the natural gut flora and also on host immunity. They interact with the intestinal epithelia and dendritic cells. There is a close interplay between this microbiome and the host immune system. It has been found that administration of probiotics in intestinal disease and certain enteric diseases can be useful in establishing intestinal homeostasis. Fecal microbiota transplant is also based on the same concept. The goal is to restore the diversity of the intestinal microbiota essential for intestinal homeostasis, reflective of a healthy person. It is effective against recurrent C. difficile infection and other gastrointestinal (GI) and non- GI tract infections.
The crucial role played by homeostatic regulation has been highlighted in this answer. Any deviations from homeostasis and inability to reinstate it, results in diseased conditions. An example of this is Type II diabetes or diabetes mellitus which is a result of inability of the body to produce enough insulin. This results in abnormally high blood sugar levels. Hyper immunity and inability to keep T cells count in check also results in chronic inflammation and organ failure (like in COVID- 19 patients). This is also an example of deviation from homeostasis. These examples highlight how important it is to maintain a balance in the body and prevent wear and tear. We can help our body maintain homeostasis by proper fluid and diet intake and regular exercise. It also increases the longevity of the organs and the body itself.
Human Physiology, Duke University, Coursera
Anatomy and Physiology, BC Campus, Rice University
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