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homeostasis Physiology • In the distant past, humans thought that good health was somehow associated with a "balance" among the multiple life-giving forces ("humours") in the body – Today we know that living tissue is composed of trillions of small cells, all are packaged to permit movement of certain substances, but not others, across the cell membrane. – also we know that cells are in contact with the interstitial fluid. • The interstitial fluid is in a state of flux, with chemicals, gases, and water moving it in two directions between the cell interiors and the blood. Fluid compartments of the body • most of the common physiological variables found in normal, healthy organisms are maintained at relatively steady states. – i.e. blood pressure, body temperature, blood oxygen, and sodium. – This is true despite external conditions that are not constant. Homeostasis defined • homeostasis is simply defined as a state of reasonably stable balance between the physiological variables – NO variable is constant over time. • Blood glucose can have dramatic swings. • Homeostasis is in DYNAMIC balance, not static. • It is relatively stable, if disturbed mechanisms can restore it to normal values. What does it mean to be relatively constant? • It depends on what is being monitored. – Arterial oxygen must be tightly controlled – Blood glucose can vary wildly • A person can be in homeostasis for one variable but not for another. – You could be in sodium homeostasis but have abnormally high levels of CO2. • This is a life threatening condition. • Just one variable out of homeostasis can have life-threatening consequences. Physiology vs. Pathophysiology • If all your major organ systems are in homeostasis, then you are in good health. • diseases take one or more systems out of homeostasis. • Physiology:When homeostasis is maintained • Pathophysiology: homeostasis is not maintained. How do you know if a variable is in homeostasis? • You have to observe a person over time to find out what is “normal.” • Not usually possible because you only go to a doctor when you are sick (out of homeostasis). – Usually, doctors rely on normal values for large populations of people. • Body temperature – Normal values are useful, but not if a person has been exercising. – There are rhythms to a person’s body temperature. Many variables are cyclical • Examples – – – – Body temperature, sleep/wake, levels of certain hormones If you took one measurement, they may be normal, but might not detect when they are abnormally high or low. • Measure over 24 hour period to get a better picture of homeostasis. Characteristics of homeostatic control systems • cells, tissue and organ activity must be integrated so that changes in the ECF initiate a reaction to correct the change. • Homeostasis, then, denotes the relatively stable conditions of the internal environment – These conditions result from compensating regulatory responses controlled by homeostatic control systems. Regulation of body temperature • Man w/ body temp. of 370 C is in room at 200 C – He is losing heat to the environment – Chemical reactions in his cells are releasing heat at a rate = to loss – Body is in a steady state but state is maintained by input of energy • Steady state is not equilibrium • Steady state temperature is the set-point Lower room temp to • This increases loss of heat from skin and body temp starts to fall – What responses will occur? • Blood vessels to skin constrict • Person curls to reduce skin surface area • Shivering occurs producing large amounts of heat 0 5 C Negative Feedback • Defined – an increase or decrease in the variable being regulated brings about responses that tend to move the variable in the direction opposite ("negative" to) the direction of the original change – It can occur at the organ, cellular, or molecular level negative feedback example Negative feedback in an enzyme pathway • When energy is needed by a cell, – glucose is converted into ATP. • The ATP that accumulates in the cell inhibits the activity of some of the enzymes involved in the conversion of glucose to ATP • As ATP levels increase within a cell, production of ATP is slowed down Not all feedback is negative • Positive feedback is less common but does occur – In nerve cells, when a stimulus is received, pore-like channels open letting Na+ in – In childbirth • The baby’s head presses against the uterus stimulating the release of oxytocin • Oxytocin causes uterine contractions, pushing the baby’s head against the uterine wall releasing more oxytocin. Feedforward regulation • While your body can respond to changes in external temperatures AFTER the body’s internal temperature changes, it can also respond to changes BEFORE your body temp. starts to fall. – Nerve cells in the skin detect changes and send information to the brain. – Often this response is a result of LEARNING Parts of homeostatic control systems- Reflexes • reflex is a specific involuntary,unlearned "built in" response to a particular stimulus – The stimulus is a detectable change in the internal or external environment. – Detected by a nerve receptor – The stimulus causes the receptor to send a signal to the integrating center (afferent) Reflex Arc Reflex part 2 • Integrating center receives signals from many receptors – Receptors may be for different kinds of stimuli – Output from center (efferent) goes to effector to alter its activity Reflex for minimizing decrease in body temperature Reflexes are not just part of the nervous system • We usually think of reflexes are part of the nervous system (hand on a hot stove), but now we include many other systems as part of reflexes. – Hormone-secreting glands serve as integrating centers – Chemical messengers travel through the blood. Intercellular chemical messengers • reflexes and other responses depend on the ability of cells to communicate w/ each other. – Most often occurs with chemical messengers. • Hormones- allow hormone secreting cell to communicate with target cells. – Blood delivers the hormone to the cell. • Neurotransmitters- allow nerve cells to communicate with each other – One nerve cell can alter the activity of another cell. – Neurotransmitters released into the area around effector cells can alter their activity. • Paracrine agents- chemical messengers in local responses Categories of chemical messengers Paracrine/autocrine agents • Paracrine agents are made by cells (given a stimulus) and released into the ECF. – Agents diffuse to neighboring cells which are their target cells. • Autocrine agents are made by a cell, released and the target cell is the one that released it. (?) Why do you care about these agents? • We are finding many different paracrine/autocrine agents that have many diverse effects. – They are not just proteins. – Secreted by many cell types in many kinds of tissues – So many that they can be organized into families • i.e. Growth factor family has 50 distinct molecules that can cause cells to divide/differentiate. Processes related to homeostasis • Some seemingly unrelated processes have implications for homeostasis – Adaptation and acclimatization – Biological rhythms – Apoptosis Adaptation/ acclimatization • Adaptation is a characteristic that favors survival in specific environments. – Your ability to respond to a specific environmental stress isn’t fixed, but it can be enhanced by prolonged exposure to the stress. – Acclimatization: A specific type of adaptationthe improved functioning of an existing homeostatic system. Acclimatization is reversible (usually) • If daily exposure to the stress is eliminated, then acclimatization is reversible… • Some acclimatizations that happen early in life may become permanent. – Natives of the Andes Mountains • Low oxygen levels cause increased chest sizes, wide nostrils, broad dental arches Biological rhythms • Many body functions are rhythmic – Occur in 24 hour (circadian rhythm) cycles – Sleep/wake, body temp., hormone levels, etc… – Are anticipatory (kind of like feedforward systems without detectors) Rhythms allow responses to occur automatically • Remember that most homeostatic responses are corrective, they occur after homeostasis is perturbed – Rhythms cause responses to occur when a challenge is likely but before it actually does. • Urinary excretion of potassium is high during the day and low at night. Body rhythms are internally driven • Environmental factors don’t drive the rhythms, but provide timing cues. – Sleeping experiment (no light cues) – Sleep/wake cycle is a free-running rhythm – Sleep/wake cycles can vary between 23-27 hours but not more or less than that. Other environmental cues • Light/dark cycle is very important, but not the only one. • External environmental temperature • Meal timing • Social cues – Sleep experiment people are separated, their cycles are each different. – Put them together and their cycles synchronize Jet Lag • Environmental time cues can phase-shift rhythms. – Going from LA to Atlanta and staying for a week. – Circadian rhythm will adjust, but it takes time – In the meantime, you suffer jet lag • Sleep disruption, gastrointestinal trouble, decreased vigilance and attention span, general malaise Neural basis of body rhythms • In the hypothalamus – A group of nerve cells (suprachiasmatic nucleus) – Acts as the pacemaker for rhythms • Pacemaker receives input from the eyes and other senses. • Then it sends signals to other parts of the brain that control other systems, activating some and inhibiting others. • Not well understood Sleep and the Pineal gland • Pacemaker sends signal to pineal gland – – – – Gland releases melatonin Pineal secretes during darkness, not daylight Melatonin influences other organs Makes you sleepy Apoptosis • Defined– The ability to self-destruct by activation of an intrinsic program within the cell • Important for – sculpting a developing organism or – Eliminating undesirable cells (cancerous) Importance of Apoptosis • Crucial for regulating the number of cells in a tissue or organ. – Control of cell number is determined by a balance between cell proliferation (addition of new cells by mitosis) and cell death (apoptosis) • Neutrophils (cells alive) How does it occur? • Controlled autodigestion of cell organelles. – Enzymes breakdown the nucleus and then other organelles • The cell membrane isn’t digested. • The cell sends out chemical signals that recruit phagocytic cells (cells that “eat” other cells). – This is different than what happens when a cell is injured (necrosis) How is it kept off? • Virtually all cells have the apoptosis enzymes. – Why aren’t they turned on? • A large number of molecules called “survivor signals” keep the cell from activating the enzymes. • So most cells are programmed to commit suicide UNLESS they receive a signal to stay alive. – Prostate gland cells will die if testosterone is not present What about cancer? Degenerative diseases? • Cancer cells undergo uncontrolled cell proliferation. – So the apoptosis enzymes are always turned off. • In degenerative diseases (osteoporosis) – The rate of cell death is higher than that of cell proliferation. • Drugs that reduce rate of apoptosis Balance in the homeostasis of chemicals • Most homeostatic systems control the balance of specific chemicals. 3 states of total body balance • Negative balance – Loss exceeds gain, total amount of substance in body is decreasing. • Positive balance – Gain exceeds loss • Stable balance – Gain equals loss Water, sodium balance • Water – Stable balance is upset with excessive sweating. – Restored by? • Sodium (Na+) – Kidneys excrete Na+ into urine in approx. = amounts of ingested daily. – If intake were to increase dramatically, kidneys will excrete more in urine, but only so much can be excreted. – If the increase is continued, it can have effects on other systems – A small change in blood sodium has been linked to hypertension. A quick summary • Homeostasis is a complex, dynamic process. – It regulates the adaptive responses of the body to changes in external and internal environments. – homeostatic systems require a sensor to detect changes and a means to produce a response. • Responses can include: muscle activity, synthesis of chemical messengers (hormones) and behavioral changes. • All responses require energy. • You get energy to respond from the food you eat.