Homeostasis and Feedback Loops Homeostasis relates to dynamic physiological processes that help us maintain an internal environment suitable for normal function. Homeostasis is not the same as chemical or physical equilibrium. Such equilibrium occurs when no net change is occurring: add milk to the coffee and eventually, when equilibrium is achieved, there will be no net diffusion of milk in the coffee mug. Homeostasis, however, is the process by which internal variables, such as body temperature, blood pressure, etc., are kept within a range of values appropriate to the system. When a stimulus changes one of these internal variables, it creates a detected signal that the body will respond to as part of its ability to carry out homeostasis. HOMEOSTASIS Homeostasis is the tendency of biological systems to maintain relatively constant conditions in the internal environment while continuously interacting with and adjusting to changes originating within or outside the system. Consider that when the outside temperature drops, the body does not just “equilibrate” with (become the same as) the environment. Multiple systems work together to help maintain the body’s temperature: we shiver, develop “goose bumps”, and blood flow to the skin, which causes heat loss to the environment, decreases. Many medical conditions and diseases result from altered homeostasis. This section will review the terminology and explain the physiological mechanisms that are associated with homeostasis. We will discuss homeostasis in every subsequent system. Many aspects of the body are in a constant state of change—the volume and location of blood flow, the rate at which substances are exchanged between cells and the environment, and the rate at which cells are growing and dividing, are all examples. But these changes actually contribute to keeping many of the body’s variables, and thus the body’s overall internal conditions, within relatively narrow ranges. For example, blood flow will increase to a tissue when that tissue becomes more active. This ensures that the tissue will have enough oxygen to support its higher level of metabolism. Maintaining internal conditions in the body is called homeostasis (from homeo-, meaning similar, and stasis, meaning standing still). The root “stasis” of the term “homeostasis” may seem to imply that nothing is happening. But if you think about anatomy and physiology, even maintaining the body at rest requires a lot of internal activity. Your brain is constantly receiving information about the internal and external environment, and incorporating that information into responses that you may not even be aware of, such as slight changes in heart rate, breathing pattern, activity of certain muscle groups, eye movement, etc. Any of these actions that help maintain the internal environment contribute to homeostasis. We can consider the maintenance of homeostasis on a number of different levels. For example, consider what happens when you exercise, which can represent challenges to various body systems. Yet instead of these challenges damaging your body, our systems adapt to the situation. At the whole-body level, you notice some specific changes: your breathing and heart rate increase, your skin may flush, and you may sweat. If you continue to exercise, you may feel thirsty. These effects are all the result of your body trying to maintain conditions suitable for normal function: Your muscle cells use oxygen to convert the energy stored in glucose into the energy stored in ATP (adenosine triphosphate), which they then use to drive muscle contractions. When you exercise, your muscles need more oxygen. Therefore, to maintain an adequate oxygen level in all of the tissues in your body, you breathe more deeply and at a higher rate when you exercise. This allows you to take in more oxygen. Your heart also pumps faster and harder, which allows it to deliver more oxygen-rich blood to your muscles and other organs that will need more oxygen and ATP. As your muscles carry out cellular respiration to release the energy from glucose, they produce carbon dioxide and water as waste products. These wastes must be eliminated to help your body maintain its fluid and pH balance. Your increased breathing and heart rates also help eliminate a great deal of carbon dioxide and some of the excess water. Your muscles use the energy stored in ATP molecules to generate the force they need to contract. A byproduct of releasing that energy is heat, so exercising increases your body temperature. To maintain an appropriate body temperature, your body compensates for the extra heat by causing blood vessels near your skin to dilate and by causing sweat glands in your skin to release sweat. These actions allow heat to more easily dissipate into the air and through evaporation of the water in sweat. As you exercise for longer periods of time, you lose more and more water and salts to sweat (and, to a smaller extent, from breathing more). If you exercise too long, your body may lose enough water and salt that its other functions begin to be affected. Low concentrations of water in the blood prompt the release of hormones that make you feel thirsty. Your kidneys also produce more concentrated urine with less water if your fluid levels are low. These actions help you maintain fluid balance. Homeostasis Terminology The maintenance of homeostasis in the body typically occurs through the use of feedback loops that control the body’s internal conditions. Feedback loop is defined as a system used to control the level of a variable in which there is an identifiable receptor (sensor), control center (integrator or comparator), effectors, and methods of communication. We use the following terminology to describe feedback loops: Variables are parameters that are monitored and controlled or affected by the feedback system. Receptors (sensors) detect changes in the variable. Control centers (integrators) compare the variable in relation to a set point and signal the effectors to generate a response. Control centers sometimes consider information other than just the level of the variable in their decisionmaking, such as time of day, age, external conditions, etc. Effectors execute the necessary changes to adjust the variable. Methods of communication among the components of a feedback loop are necessary in order for it to function. This often occurs through nerves or hormones, but in some cases receptors and control centers are the same structures, so that there is no need for these signaling modes in that part of the loop. Terminology in this area is often inconsistent. For example, there are cases where components of a feedback loop are not easily identifiable, but variables are maintained in a range. Such situations are still examples of homeostasis and are sometimes described as a feedback cycle instead of a feedback loop. Feedback Cycle is defined as any situation in which a variable is regulated and the level of the variable impacts the direction in which the variable changes (i.e. increases or decreases), even if there is not clearly identified loop components. With this terminology in mind, homeostasis then can be described as the totality of the feedback loops and feedback cycles that the body incorporates to maintain a suitable functioning status. Feedback Loops Remember that homeostasis is the maintenance of a relatively stable internal environment. When a stimulus, or change in the environment, is present, feedback loops respond to keep systems functioning near a set point, or ideal level. Feedback is a situation when the output or response of a loop impacts or influences the input or stimulus. Typically, we divide feedback loops into two main types: 1. Positive feedback loops, in which a change in a given direction causes additional change in the same direction. For example, an increase in the concentration of a substance causes feedback that produces continued increases in concentration. 2. Negative feedback loops, in which a change in a given direction causes change in the opposite direction. For example, an increase in the concentration of a substance causes feedback that ultimately causes the concentration of the substance to decrease. Positive feedback loops are inherently unstable systems. Because a change in an input causes responses that produce continued changes in the same direction, positive feedback loops can lead to runaway conditions. The term positive feedback is typically used as long as a variable has an ability to amplify itself, even if the components of a loop (receptor, control center and effector) are not easily identifiable. In most cases, positive feedback is harmful, but there are a few instances where positive feedback, when used in limited fashion, contributes to normal function. For example, during blood clotting, a cascade of enzymatic proteins activates each other, leading to the formation of a fibrin clot that prevents blood loss. One of the enzymes in the pathway, called thrombin, not only acts on the next protein in the pathway but also has an ability to activate a protein that preceded it in the cascade. This latter step leads to a positive feedback cycle, where an increase in thrombin leads to further increases in thrombin. It should be noted that there are other aspects of blood clotting that keep the overall process in check, such that thrombin levels don’t rise without limit. But if we just consider the effects of thrombin on itself, it is considered a positive feedback cycle. Although some may consider this a positive feedback loop, such terminology is not universally accepted. Negative feedback loops are inherently stable systems. Negative feedback loops, in conjunction with the various stimuli that can affect a variable, typically produce a condition in which the variable oscillates around the set point. For example, negative feedback loops involving insulin and glucagon help to keep blood glucose levels within a narrow concentration range. If glucose levels get too high, the body releases insulin into the bloodstream. Insulin causes the body’s cells to take in and store glucose, lowering the blood glucose concentration. If blood glucose gets too low, the body releases glucagon, which causes the release of glucose from some of the body’s cells. Positive Feedback In a positive feedback mechanism, the output of the system stimulates the system in such a way as to further increase the output. Common terms that could describe positive feedback loops or cycles include “snowballing” and “chain reaction”. Without a counter-balancing or “shut-down” reaction or process, a positive feedback mechanism has the potential to produce a runaway process. As noted, there are some physiologic processes that are commonly considered to be positive feedback, although they may not all have identifiable components of a feedback loop. In these cases, the positive feedback loop always ends with counter-signaling that suppresses the original stimulus. Air conditioning is a technological system that can be described in terms of a feedback loop. The thermostat senses the temperature, an electronic interface compares the temperature against a set point (the temperature that you want it to be). If the temperature matches or is cooler, then nothing happens. If the temperature is too hot, then the electronic interface triggers the air-conditioning unit to turn on. Once the temperature is lowered sufficiently to reach the set point, the electronic interface shuts the air-conditioning unit off This is an example of a _________________________ feedback loop. Cruise control is another technological feedback system. The idea of cruise control is to maintain a constant speed in your car. The car’s speed is determined by the speedometer and an electronic interface measures the car’s speed against a set point chosen by the driver. If the speed is too slow, the interface stimulates the engine; if the speed is too fast, the interface reduces the power to the tires. This is an example of a ________________________ feedback loop. A good example of a ____________________ feedback involves the amplification of labor contractions. The contractions are initiated as the baby moves into position, stretching the cervix beyond its normal position. The feedback increases the strength and frequency of the contractions until the baby is born. After birth, the stretching stops and the loop is interrupted. Another example of a ________________________ feedback occurs in lactation, during which a mother produces milk for her infant. During pregnancy, levels of the hormone prolactin increase. Prolactin normally stimulates milk production, but during pregnancy, progesterone inhibits milk production. At birth, when the placenta is released from the uterus, progesterone levels drop. As a result, milk production surges. As the baby feeds, its suckling stimulates the breast, promoting further release of prolactin, resulting in yet more milk production. This positive feedback ensures the baby has sufficient milk during feeding. When the baby is weaned and no longer nurses from the mother, stimulation ceases and The above provide examples of beneficial positive feedback mechanisms. However, in many instances, positive feedback can be potentially damaging to life processes. For example, blood pressure can fall significantly if a person loses a lot of blood due to trauma. Blood pressure is a regulated variable that leads to the heart increasing its rate (i.e. heart rate increases) and contracting more strongly. These changes to the heart cause it to need more oxygen and nutrients, but if the blood volume in the body is too low, the heart tissue itself will not receive enough blood flow to meet these increased needs. The imbalance between oxygen demands of the heart and oxygen supply can lead to further heart damage, which actually lowers blood pressure, providing a larger change in the variable (blood pressure). The loop responds by trying to stimulate the heart even more strongly, leading to further heart damage…and the loop goes on until death ensues. Negative Feedback Most biological feedback systems are negative feedback systems. Negative feedback occurs when a system’s output acts to reduce or dampen the processes that lead to the output of that system, resulting in less output. In general, negative feedback loops allow systems to self-stabilize. Negative feedback is a vital control mechanism for the body’s homeostasis. Terms Applied to Temperature: Consider one of the feedback loops that controls body temperature. Variable: In this instance, the variable is body temperature. Receptors: Thermo receptors detect changes in body temperature. For example, thermo receptors in your internal organs can detect a lowered body temperature and produce nerve impulses that travel to the control center, the hypothalamus. Control Center: The hypothalamus controls a variety of effectors that respond to a decrease in body temperature. Effectors: There are several effectors controlled by the hypothalamus. o blood vessels near the skin constrict, reducing blood flow (and the resultant heat loss) to the environment. o Skeletal muscles are also effectors in this feedback loop: they contract rapidly in response to a decrease in body temperature. This shivering helps to generate heat, which increases body temperature. This is an important example of how a negative feedback loop maintains homeostasis is the body’s thermoregulation mechanism. The body maintains a relatively constant internal temperature to optimize chemical processes. Neural impulses from heatsensitive thermoreceptors in the body signal the hypothalamus. The hypothalamus, located in the brain, compares the body temperature to a set point value. When body temperature drops, the hypothalamus initiates several physiological responses to increase heat production and conserve heat: Narrowing of surface blood vessels (vasoconstriction) decreases the flow of heat to the skin. Shivering commences, increasing production of heat by the muscles. Adrenal glands secrete stimulatory hormones such as norepinephrine and epinephrine to increase metabolic rates and hence heat production. These effects cause body temperature to increase. When it returns to normal, the hypothalamus is no longer stimulated, and these effects cease. When body temperature rises, the hypothalamus initiates several physiological responses to decrease heat production and lose heat: Widening of surface blood vessels (vasodilation) increases the flow of heat to the skin and get flushed. Sweat glands release water (sweat) and evaporation cools the skin. These effects cause body temperature to decrease. When it returns to normal, the hypothalamus is no longer stimulated, and these effects cease. Many homeostatic mechanisms, like temperature, have different responses if the variable is above or below the set point. When temperature increases, we sweat, when it decreases, we shiver. These responses use different effectors to adjust the variable. In other cases, a feedback loop will use the same effector to adjust the variable back toward the set point, whether the initial change of the variable was either above or below the set point. CASE STUDY: Diabetes: Type 1 and Type 2 An important example of negative feedback is the control of blood sugar. 1. After a meal, the small intestine absorbs glucose from digested food. Blood glucose levels rise. 2. Increased blood glucose levels stimulate beta cells in the pancreas to produce insulin. 3. Insulin triggers liver, muscle, and fat tissue cells to absorb glucose, where it is stored. As glucose is absorbed, blood glucose levels fall. 4. Once glucose levels drop below a threshold, there is no longer a sufficient stimulus for insulin release, and the beta cells stop releasing insulin. Due to synchronization of insulin release among the beta cells, basal insulin concentration oscillates in the blood following a meal. The oscillations are clinically important, since they are believed to help maintain sensitivity of insulin receptors in target cells. This loss of sensitivity is the basis for insulin resistance. Thus, failure of the negative feedback mechanism can result in high blood glucose levels, which have a variety of negative health effects. Let’s take a closer look at diabetes. In particular, we will discuss diabetes type 1 and type 2. Diabetes can be caused by too little insulin, resistance to insulin, or both. Type 1 Diabetes occurs when the pancreatic beta cells are destroyed by an immunemediated process. Because the pancreatic beta cells sense plasma glucose levels and respond by releasing insulin, individuals with type 1 diabetes have a complete lack of insulin. In this disease, daily injections of insulin are needed. Also affected are those who lose their pancreas. Once the pancreas has been removed (because of cancer, for example), diabetes type 1 is always present. Type 2 Diabetes is far more common than type 1. It makes up most of diabetes cases. It usually occurs in adulthood, but young people are increasingly being diagnosed with this disease. In type 2 diabetes, the pancreas still makes insulin, but the tissues do not respond effectively to normal levels of insulin, a condition termed insulin resistance. Over many years the pancreas will decrease the levels of insulin it secretes, but that is not the main problem when the disease initiates. Many people with type 2 diabetes do not know they have it, although it is a serious condition. Type 2 diabetes is becoming more common due to increasing obesity and failure to exercise, both of which contribute to insulin resistance. While you are reading, consider these questions below: 1. Define homeostasis. 2. Why is homeostasis different from equilibrium? 3. List and describe 2 ways your body responds to exercise to maintain homeostasis. 4. What are the 4 parts of a feedback loop? List and describe/define them. 5. How does communication throughout a feedback loop work? 6. Compare and contrast positive and negative feedback loops. 7. Which type of feedback loop is generally more stable? Why? Explain. 8. Air conditioning is an example of a (positive or negative) feedback loop? 9. A woman having labor contractions is an example of a (positive or negative) feedback loop. For this example, identify the variable, receptor, control center, and effector. 10. Regulating blood sugar is an example of example of a (positive or negative) feedback loop. For this example, identify the variable, receptor, control center, and effector.