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Chapter 8: Homeostasis and Cellular Function

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8.1 The Concept of Homeostasis

8.2 Disease as a Homeostatic Imbalance

8.3 Measuring Homeostasis to Evaluate Health

8.4 Solubility

8.5 Solution Concentration

8.5.1 Molarity8.5.2 Parts Per Solutions8.5.3 Equivalents

8.6 Dilutions

8.7 Ion Concentrations in Solution

8.8 Movement of Molecules Across the Membrane

8.9 Summary

8.10 References

8.1 The Concept of Homeostasis

Homeostasis refers to the body’s ability to physiologically regulate its inner environment to ensure its stability in response to fluctuations in external or internal conditions. The liver, the pancreas, the kidneys, and the brain (hypothalamus, the autonomic nervous system and the endocrine system) help maintain homeostasis. The liver is responsible for metabolizing toxic substances and with signaling from the pancreas maintains carbohydrate metabolism. The liver also helps to regulate lipid metabolism and is the primary site of cholesterol production. The kidneys are responsible for regulating blood water levels, re-absorption of substances into the blood, maintenance of salt and ion levels in the blood, regulation of blood pH, and excretion of urea and other waste products. The hypothalamus is involved in the regulation of body temperature, heart rate, blood pressure, and circadian rhythms (which include wake/sleep cycles).

Homeostasis can be influenced by either internal or existing conditions (instrinsic factors) or external or environmental conditions (extrinsic factors) and is maintained by many different mechanisms. All homeostatic control mechanisms have at least three interdependent components for the variable being regulated:

sensor integrating centereffector

The sensors, integrating center, and effectors are the basic components of every homeostatic response. Positive and negative feedback are more complicated mechanisms that enable these three basic components to maintain homeostasis for more complex physiological processes.

Negative Feedback

Negative feedback mechanisms use one of the products of the reaction to reduce the output or activity of the process for the purpose of returning an organ or system to its normal range of functioning. Most homeostatic processes use negative feedback regulation to maintain a specific parameter around a setpoint range that supports life Figure 8.1. However, it should be noted that negative feedback processes are also used for other processes that are not homeostatic.

Within the realm of homeostasis, temperature control is a good example that uses negative feedback. Nerve cells (the sensors) relay information about body temperature to the hypothalamus (the integrating center). The hypothalamus then signals several effectors to return the body temperature to 37oC (the set point). Two effectors activated in the process when core temperature is too high are the sweat glands which serve to cool the skin and the blood vessels which undergo vasodilation (or enlarging) so the body can give off more heat. Once the core temperature is brought back into normal range, the sensor will send negative feedback messages to the integrating center to turn off the process (ie turn off the sweat glands and inhibit further vasodilation). Both internal and external events can induce negative feedback mechanisms. The two examples above represent internal mechanisms utilized to return the body within the normal temperature range. However, we can also mediate the cooling of the body through external factors, such as removing a warm hat and gloves or pouring a cool glass of water over our head. Both external and internal mechanisms for cooling can return the temperature of the body to within the normal range and elicit the negative feedback response. Similarly, if body temperature is below the set point, muscles shiver to generate heat and the constriction of the blood vessels helps the body retain heat.

Homeostatic processes are very complex because the setpoint or normal range might change depending on the circumstance. For example, the hypothalamus can change the body’s temperature set point, such as raising it during a fever to help fight an infection.

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Figure 8.1 Homeostatic Regulation of Temperature in Humans. Core body temperature is maintained at a normal setpoint of 37oC. If the core temperature rises above (right hand side) or drops below (left hand side) the setpoint, internal biological responses are initiated to return the core temperature back to the setpoint range. Once this is achieved, negative feedback loops are initiated to down regulate the internal biological responses so that the core temperature doesn’t overshoot the required change.

This Figure is adapted from: The Kahn Academy

Positive Feedback

Positive feedback is a mechanism in which an activated component enhances or further upregulates the process that gave rise to itself in order to create an even stronger response. Positive feedback mechanisms are designed to accelerate or enhance the output created by a stimulus that has already been activated. Positive feedback mechanisms are designed to push levels out of normal ranges and are not used as often in homeostatic responses. To achieve positive feedback, a series of events initiates a cascading process that builds to increase the effect of the stimulus.

An example of a positive feedback loop is the blood clotting cascade which is originally initiated by external damage to the vasculature (Figure 8.2). During a damage event, extrinsic factors begin the initiation of the blood clotting cascade. The proteins involved in this process are usually held inactive by being produced in a much larger form than is required. To activate the protein, the protein needs to be cleaved into a smaller, active complex. When a protein is held in a large inactive state and cleaved to yield the active component, it is called a zymogen. The blood clotting cascade contains many zymogens. The first zymogen to be activated is Factor X. When Factor X is cleaved, it becomes active and proceeds to cleave the next downstream target, Prothrombin II. This produces the active component, Thrombin IIa which has multiple effects. First, it cleaves the protein Fibrinogen to produce Fibrin. Fibrin then begins to form a clotting complex with itself. This is referred to as the loose mesh network. Activated Thrombin IIa also cleaves the inactive form of Factor XIII. Activated Factor XIIIa causes crosslinks to form in the loose mesh network creating the finalized stable mesh that forms the blood clot. To accelerate this process further, Thrombin IIa also has two positive feedback effects. It can also cleave Inactive Factor X creating more activated Factor X and ultimately more activated Throbmin IIa. It also increases the activity of the instrinsic blood clotting cascade, which further upregulates the activation of Factor X.

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Figure 8.2 The Positive Feedback Mechanism of the Blood Clotting Cascade. Extrinsic factors such as damage or injury activated the cleavage of zymogen proteins in the blood clotting cascade. Activation of the zymogen, Thrombin IIa begins the formation of the fibrin clotting network and also elicits positive feedback that further upregulates the entire clotting cascade.

This Figure is adapted from: MPT-Matthew

Many parameters are regulated within the body within a narrow homeostatic window to maintain proper functioning and balance within biological systems. Some examples of homeostatic parameters include:

Temperature

Humans are warm-blooded or endothermic, maintaining a near-constant body temperature. Thermoregulation is an important aspect of human homeostasis. Heat is mainly produced by the liver and muscle contractions. Humans have been able to adapt to a great diversity of climates, including hot humid and hot arid environments. High temperatures pose serious stresses for the human body, placing it in great danger of injury or even death. In order to deal with these climatic conditions, humans have developed physiologic and cultural modes of adaptation. When internal temperature reaches extremes of 45°C (113°F), hyperthermia, a condition where an individual’s body temperature is elevated beyond normal, occurs and cellular proteins will denature, causing metabolism to stop and ultimately lead to death. Hypothermia is the opposite condition, where internal body temperature falls below homeostatic norms. Hypothermia occurs when body core temperatures fall below 35.0 °C (95.0 °F). Symptoms depend on the temperature. In mild hypothermia there is shivering and mental confusion. In moderate hypothermia shivering stops and confusion increases. In severe hypothermia, there may be paradoxical undressing, in which a person removes their clothing, as well as an increased risk of the heart stopping. Hypothermia has two main types of causes. It classically occurs from exposure to extreme cold. It may also occur from any condition that decreases heat production or increases heat loss. Commonly this includes alcohol intoxication but may also include low blood sugar, anorexia, and advanced age. 

Iron

Iron is an essential element for human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease. Hematologists have been especially interested in the system of iron metabolism because iron is essential to red blood cells. In fact, most of the human body’s iron is contained in red blood cells’ hemoglobin protein where it aids in the binding and transport of oxygen for cellular respiration, and iron deficiency is the most common cause of anemia.

When body levels of iron are too low, an iron-sensitive hormone called hepcidin is decreased in the duodenal epithelium (lining of the small intestine). This causes an increase in ferroportin activity, an iron-selective protein channel embedded in the membrane of intestinal cells. Activation of this channel stimulates iron uptake in the digestive system. An iron surplus will stimulate the reverse of this process.

Sugar

Blood glucose is regluated with two hormones, insulin and glucagon, both released from the pancreas.

When blood sugar levels become too high, insulin is released from the pancreas. Glucose, or sugar, is taken up by cells (especially liver and muscle tissue) where it is stored as glycogen. This results in a lowering of the blood sugar levels. On the other hand, when blood sugar levels become too low, glucagon is released by the pancreas. It promotes the breakdown of glycogen into the glucose monomers within liver cells. The liver cells then release free glucose back into the blood stream and restore blood sugar levels.

Improper glucagon functioning results in hypoglycemia, a condition where blood sugar is too low. This can be life threatening leading to coma and death if not treated promptly. Improper insulin function results in hyperglycemia or increased blood sugar levels. If this state is prolonged the disease called diabetes results. Diabetes will be discussed in more detail in section 8.2 below.

Osmoregulation

Osmoregulation is the active regulation of the osmotic pressure of bodily fluids to maintain the homeostasis of the body’s water content; that is it keeps the body’s fluids from becoming too dilute or too concentrated. Osmotic pressure is a measure of the tendency of water to move into one solution from another by osmosis. The higher the osmotic pressure of a solution the more water wants to go into the solution.

The kidneys are used to remove excess ions (such as Na+, K+ and Ca2+) from the blood, thus affecting the osmotic pressure. These are then expelled as urine. The kidneys are also important for maintaining acid/base levels, such that the pH of the blood remains close to the neutral point.

Water Volume

The kidneys also determine the overall water volume maintained within the body. The hormones Anti-Diuretic Hormone (ADH), also known as vasopressin, and Aldosterone play a major role in regulating kidney function.

deficientexcessive
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Figure 8.3: Effects of Aldosterone and ADH on Kidney Function. When fluid levels in the body are low, ADH (Vasopressin) is secreted by the pituitary gland and Aldosterone is secreted by the adrenal glands. ADH decreases the loss of water whereas Aldosterone increases the reabsorbtion of Na+ within the collecting duct of the kidneys. Water is reabsorbed with the Na+ causing an increase in fluid retention and decreased urine output.

This figure has been modified from: EEOC and Wikimedia Commons.

Hemostasis

Hemostasis is the process whereby bleeding is halted. A major part of this is the coagulation cascade highlighted in Figure 8.2.

Platelet accumulation causes blood clotting in response to a break or tear in the lining of blood vessels. Unlike the majority of control mechanisms in human body, the hemostasis utilizes positive feedback, for the more the clot grows, the more clotting occurs, until the blood stops.

Sleep

Sleep timing depends upon a balance between homeostatic sleep propensity, the need for sleep as a function of the amount of time elapsed since the last adequate sleep episode, and circadian rhythms which determine the ideal timing of a correctly structured and restorative sleep episode. A sleep deficit will elicit a compensatory increase in the intensity and duration of sleep, while excessive sleep reduces sleep propensity.

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8.2 Disease as a Homeostatic Imbalance

What Is Disease?

Disease is any failure of normal physiological function that leads to negative symptoms. While disease is often a result of infection or injury, most diseases involve the disruption of normal homeostasis. Anything that prevents positive or negative feedback system from working correctly could lead to disease if the mechanisms of disruption become strong enough.

Aging is a general example of disease as a result of homeostatic imbalance. As an organism ages, weakening of feedback loops gradually results in an unstable internal environment. This lack of homeostasis increases the risk for illness and is responsible for the physical changes associated with aging. Heart failure is the result of negative feedback mechanisms that become overwhelmed, allowing destructive positive feedback mechanisms to compensate for the failed feedback mechanisms. This leads to high blood pressure and enlargement of the heart, which eventually becomes too stiff to pump blood effectively, resulting in heart failure. Severe heart failure can be fatal.

Diabetes: A Disease of Failed Homeostasis

Diabetes, a metabolic disorder caused by excess blood glucose levels, is a key example of disease caused by failed homeostasis. In ideal circumstances, homeostatic control mechanisms should prevent this imbalance from occurring. However, in some people, the mechanisms do not work efficiently enough or the amount of blood glucose is too great to be effectively managed. In these cases, medical intervention is necessary to restore homeostasis and prevent permanent organ damage.

Normal Blood Sugar Regulation

The human body maintains constant levels of glucose throughout the day. After a meal, blood glucose levels rise, as glucose is transported from the small intestine into the blood stream. In response to this, the pancreas (the sensor) releases insulin into the bloodstream where it acts as a hormone. As you learned in Chapter 6, hormones are molecules that are made in one part of the body, secreted into the bloodstream and are transported to a distant part of the body, where they mediate an effect or reaction at that secondary target. Insulin is a peptide hormone that is released by the pancreas in response to elevated levels of blood glucose. Insulin binds with high efficiency to receptor proteins on the surface of liver cells, where it turns on signaling within the liver to increase the uptake of glucose from the bloodstream (Figure 8.4). Other body cells, such as skeletal muscle, adipose tissue, and brain cells are also activated by insulin. When a molecule has multiple different effects on the body, these multiple effects are called pleiotropic effects. These other cell types will also take up glucose to use as an energy source. This lowers blood glucose levels back to normal levels. The liver can take up more glucose than other tissue types and convert it into a large carbohydrate molecule called glycogen, that you learned about in Chapter 6. It is stored as this carbohydrate until glucose is needed when it can then be broken down to released back into the blood stream. Up to 10% of the volume in liver cells is in the form of glycogen.

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Figure 8.4 Glucose Homeostasis. When blood sugar rises due to a meal (Path 1), the pancreas senses the increase in blood glucose levels. In response, it releases the peptide hormone, insulin. Insulin interacts with downstream target cells in the body, including liver and muscle tissue, where it causes the uptake of glucose from the blood stream into the cell. The excess glucose is stored as the carbohydrate, glycogen. This returns blood glucose levels back to normal. If it has been several hours after eating a mean, blood glucose levels will begin to fall (Path 2). This signals liver cells to breakdown glycogen into glucose monomers. The glucose can then be realeased back into the bloodstream.

Figure is by: Shannan Muskopf from Biologycorner.com

In between meals or during times of fasting, blood glucose levels begin to drop. This activates the pancreas to secrete a different hormone, called glucagon. Glucagon signaling activates the liver to begin breaking down the glycogen storage molecule into free glucose. The glucose is then released back into the blood stream, increasing blood glucose levels (Figure 8.4).

Over the course of a day, blood glucose levels will fluctuate modestly around the homeostatic set point (Figure 8.5). As meals are eaten, this triggers a rise in blood glucose that is counteracted by the secretion of insulin. In between meals, blood glucose levels fall, and glucagon is released by the pancreas to signal to the liver to release glucose back into the blood stream.