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The number of action potentials transmitted in the lateral pathways is further decreased by inhibitory inputs from inhibitory interneurons stimulated by the central neuron medications pain pills order naltrexone 50mg on line. Although the lateral afferent neurons (A and C) also exert inhibition on the central pathway medications jokes naltrexone 50mg for sale, their lower initial firing frequency has a smaller inhibitory effect on the central pathway medicine to stop contractions order naltrexone 50 mg online. Lateral inhibition can be demonstrated by pressing the tip of a pencil against your finger medications ms treatment discount naltrexone american express. Exact localization is possible because lateral inhibition removes the information from the peripheral regions medications for factor 8 buy genuine naltrexone online. Lateral inhibition is utilized to the greatest degree in the pathways providing the most accurate localization medications depression discount 50mg naltrexone otc. For example, lateral inhibition within the retina of the eye creates amazingly sharp visual acuity, and skin hair movements are also well-localized due to lateral inhibition between parallel pathways ascending to the brain. On the other hand, neuronal pathways carrying temperature and pain information do not have significant lateral inhibition, so we locate these stimuli relatively poorly. Once this location is known, the brain can interpret the firing frequency of neuron B to determine stimulus intensity. Because the central fiber B at the beginning of the pathway (bottom of figure) is firing at the highest frequency, it inhibits the lateral neurons (via inhibitory interneurons) to a greater extent than the lateral neurons inhibit the central pathway. Skin Area of receptor activation In some cases, for example, in the pain pathways, the afferent input is continuously inhibited to some degree. This provides the flexibility of either removing the inhibition, so as to allow a greater degree of signal transmission, or increasing the inhibition, so as to block the signal more completely. Therefore, the sensory information that reaches the brain is significantly modified from the basic signal originally transduced into action potentials at the sensory receptors. The neuronal pathways within which these modifications take place are described next. The sensory unit under the tip inhibits additional stimulated units at the edge of the stimulated area. Lateral inhibition produces a central area of excitation surrounded by an area in which the afferent information is inhibited. The sensation is localized to a more restricted region than that in which all three units are actually stimulated. Central Control of Afferent Information All sensory signals are subject to extensive modification at the various synapses along the sensory pathways before they reach higher levels of the central nervous system. The reticular formation and cerebral cortex (see Chapter 6), in particular, control the input of afferent information via descending pathways. These chains of neurons travel in bundles of parallel pathways carrying information into the central nervous system. Some pathways terminate in parts of the cerebral cortex responsible for conscious recognition of the incoming information; others carry information not consciously perceived. Sensory pathways are also called ascending pathways because they project "up" to the brain. The central processes of the afferent neurons enter the brain or spinal cord and synapse upon interneurons there. The interneurons upon which the afferent neurons synapse are called second-order neurons, and these in turn synapse with third-order neurons, and so on, until the information (coded action potentials) reaches the cerebral cortex. Most sensory pathways convey information about only a single type of sensory information. For example, one pathway conveys information only from mechanoreceptors, whereas another is influenced by information only from thermoreceptors. The olfactory cortex is located toward the midline on the undersurface of the frontal lobes (not visible in this picture). Association areas are not part of sensory pathways, but have related functions described shortly. In other words, they indicate that something is happening, without specifying just what or where. A given ascending neuron in a nonspecific ascending pathway may respond, for example, to input from several afferent neurons, each activated by a different stimulus, such as maintained skin pressure, heating, and cooling. The nonspecific ascending pathways, as well as collaterals from the specific ascending pathways, end in the brainstem reticular formation and regions of the thalamus and Cerebral cortex Thalamus and brainstem information even though all of it is being transmitted by essentially the same signal, the action potential. The ascending pathways in the spinal cord and brain that carry information about single types of stimuli are known as the specific ascending pathways. Thus, information from receptors on the right side of the body is transmitted to the left cerebral hemisphere, and vice versa. The specific ascending pathways that transmit information from somatic receptors project to the somatosensory cortex. Somatic receptors are those carrying information from the skin, skeletal muscle, bones, tendons, and joints. The specific ascending pathways from the eyes connect to a different primary cortical receiving area, the visual cortex, which is in the occipital lobe. The specific ascending pathways from the ears go to the auditory cortex, which is in the temporal lobe. Specific ascending pathways from the taste buds pass to the gustatory cortex adjacent to the region of the somatosensory cortex where information from the face is processed. The pathways serving olfaction project to portions of the limbic system and the olfactory cortex, which is located on the undersurface of the frontal and temporal lobes. Finally, the processing of afferent information does not end in the primary cortical receiving areas but continues from these areas to association areas in the cerebral cortex where complex integration occurs. Sensory Physiology 197 cerebral cortex that are not highly discriminative but are important in controlling alertness and arousal. The cortical association areas are not considered part of the sensory pathways, but they have some functions in the progressively more complex analysis of incoming information. Although neurons in the earlier stages of the sensory pathways are necessary for perception, information from the primary sensory cortical areas undergoes further processing after it is relayed to a cortical association area. The region of association cortex closest to the primary sensory cortical area processes the information in fairly simple ways and serves basic sensory-related functions. Regions farther from the primary sensory areas process the information in more complicated ways. These include, for example, greater contributions from areas of the brain serving arousal, attention, memory, and language. Some of the neurons in these latter regions also integrate input concerning two or more types of sensory stimuli. Thus, an association area neuron receiving input from both the visual cortex and the "neck" region of the somatosensory cortex may integrate visual information with sensory information about head position. Axons from neurons of the parietal and temporal lobes go to association areas in the frontal lobes and other parts of the limbic system. Through these connections, sensory information can be invested with emotional and motivational significance. For example, stretch receptors in the walls of some of the largest blood vessels monitor blood pressure as part of reflex regulation of this pressure, but people usually do not have a conscious awareness of their blood pressure. Damaged neural networks may give faulty perceptions as in the phenomenon known as phantom limb, in which a limb lost by accident or amputation is experienced as though it were still in place. The missing limb is perceived to be the site of tingling, touch, pressure, warmth, itch, wetness, pain, and even fatigue. It seems that the sensory neural networks in the central nervous system that are normally triggered by receptor activation are, instead, activated independently of peripheral input. The activated neural networks continue to generate the usual sensations, which the brain perceives as arising from the missing receptors. In fact, the most dramatic examples of a clear difference between the real world and our perceptual world can be found in drug-induced hallucinations. Various types of mental illness can alter perceptions of the world, like the auditory hallucinations that can occur in the disease schizophrenia (discussed in detail in Chapter 8). Factors such as emotions, personality, and experience can influence perceptions so that two people can be exposed to the same stimuli and yet perceive them differently. Not all information entering the central nervous system gives rise to conscious sensation. Actually, this is a very good thing because many unwanted signals are generated by the extreme sensitivity of our sensory receptors. It is possible to detect one action potential generated by a certain type of mechanoreceptor. Although these receptors are capable of giving rise to sensations, much of their information is canceled out by receptor or central mechanisms to be discussed later. In other afferent pathways, information is not canceled out-it simply does 198 Chapter 7 In summary, for perception to occur, there can be no separation of the three processes involved-transducing stimuli into action potentials by the receptor, transmitting information through the nervous system, and interpreting those inputs. We conclude our introduction to sensory system pathways and coding with a summary of the general principles of sensory stimulus processing (Table 7. In the next section, we will take a detailed look at mechanisms involved in specific sensory systems. Sensory processing begins with the transformation of stimulus energy into graded potentials and then into action potentials in neurons. Information carried in a sensory system may or may not lead to a conscious awareness of the stimulus. Receptors translate information from the external and internal environments into graded potentials. Receptors may be either specialized endings of afferent neurons or separate cells that form synapses with the afferent neurons. Receptors respond best to one form of stimulus, but they may respond to other forms if the stimulus intensity is abnormally high. Regardless of how a specific receptor is stimulated, activation of that receptor can only lead to perception of one type of sensation. The transduction process in all sensory receptors involves-either directly or indirectly-the opening or closing of ion channels in the receptor. General classes of receptor types include mechanoreceptors, thermoreceptors, photoreceptors, and chemoreceptors. Information in sensory pathways is organized such that initial cortical processing of the various modalities occurs in different parts of the brain. Detecting stimulus duration occurs in two general ways, determined by a receptor property called adaptation. Some sensory receptors respond and generate receptor potentials the entire time that a stimulus is applied (slowly adapting, or tonic receptors), while others respond only briefly when a stimulus is first applied and sometimes again when the stimulus is removed (rapidly adapting, or phasic receptors). Sensory receptor potential amplitude tends to be graded according to the size of the stimulus applied, but action potential amplitude does not change with stimulus intensity. Rather, increasing stimulus intensity is encoded by the activation of increasing numbers of sensory neurons (recruitment) and by an increase in the frequency of action potentials propagated along sensory pathways. Stimuli of a given modality from a particular region of the body generally travel along dedicated, specific neural pathways to the brain, referred to as labeled lines. The acuity with which a stimulus can be localized depends on the size and density of receptive fields in each body region. Most specific ascending pathways synapse in the thalamus on the way to the cerebral cortex after crossing the midline, such that sensory information from the right side of the body is generally processed on the left side of the brain, and vice versa. A consciously perceived stimulus is referred to as a sensation, and awareness of a stimulus combined with understanding of its meaning is called perception. This higher processing of sensory information occurs in association areas of the cerebral cortex. Receptor potential magnitude and action potential frequency increase as stimulus strength increases. Receptor potential magnitude varies with stimulus strength, rate of change of stimulus application, temporal summation of successive receptor potentials, and adaptation. Nonspecific ascending pathways convey information from more than one type of sensory unit to the brainstem reticular formation and regions of the thalamus that are not part of the specific ascending pathways. Information from the primary sensory cortical areas is elaborated after it is relayed to a cortical association area. The primary sensory cortical area and the region of association cortex closest to it process the information in fairly simple ways and serve basic sensory-related functions. Regions of association cortex farther from the primary sensory areas process the sensory information in more complicated ways. Processing in the association cortex includes input from areas of the brain serving other sensory modalities, arousal, attention, memory, language, and emotions. The type of stimulus perceived is determined in part by the type of receptor activated. Stimulus intensity is coded by the rate of firing of individual sensory units and by the number of sensory units activated. Localization of a stimulus depends on the size of the receptive field covered by a single sensory unit and on the overlap of nearby receptive fields. Lateral inhibition is a means by which ascending pathways increase sensory acuity. Information coming into the nervous system is subject to modification by both ascending and descending pathways. Afferent neurons, which usually have more than one receptor of the same type, are the first neurons in sensory pathways. The receptive field for a neuron is the area of the body that causes activity in a sensory unit or other neuron in the ascending pathway of that unit. Neurons in the specific ascending pathways convey information about only a single type of stimulus to specific primary receiving areas of the cerebral cortex. Describe the general process of transduction in a receptor that is a cell separate from the afferent neuron. Include in your description the following terms: specificity, stimulus, receptor potential, synapse, neurotransmitter, graded potential, and action potential.

When light strikes the chromophore (retinal) of the photopigment treatment 1st degree burns buy discount naltrexone 50 mg line, it changes conformation and dissociates from the opsin medicine wheel discount naltrexone 50mg overnight delivery. In fact medicine garden naltrexone 50 mg, all of these proteins are densely interspersed within the cone disc membrane treatment of strep throat buy naltrexone online. As long as you remain in bright light symptoms juvenile diabetes order naltrexone once a day, the rods are unresponsive so that only the less-sensitive cones are operating symptoms zoloft overdose order naltrexone with amex, and the image is sharp and not overwhelmingly bright. In the low levels of illumination of the darkened room, vision can only be supplied by the rods, which have greater sensitivity than the cones. During the exposure to bright light, however, the rhodopsin in the rods has been completely activated and retinal has dissociated from the opsin, making the rods insensitive to further stimulation by light. Rhodopsin cannot respond fully again until it is restored to its resting state by enzymatic reassociation of retinal with the opsin, a process requiring several minutes. Obtaining sufficient dietary vitamin A is essential for good night vision because it provides the chromophore retinal for rhodopsin. Initially, the eye is extremely sensitive to light as rods are overwhelmingly activated, and the visual image is too bright and has poor contrast. However, the rhodopsin is soon inactivated (sometimes said to be "bleached") as retinal dissociates 210 Chapter 7 Neural Pathways of Vision the distinct characteristics of the visual image are transmitted through the visual system along multiple, parallel pathways. We just described in detail how the presence or absence of light influences photoreceptor cell membrane potential, and we will now consider how this information is encoded, processed, and transmitted to the brain. Bipolar and Ganglion Cells Light signals are converted into action potentials through the interaction of photoreceptors with bipolar cells and ganglion cells. Ganglion cells, however, do have those ion channels and are therefore the first cells in the pathway where action potentials can be initiated. Light striking the photoreceptors of either pathway hyperpolarizes the photoreceptors, resulting in a decrease in glutamate release onto bipolar cells. When the bipolar cells are hyperpolarized, they are prevented from releasing excitatory neurotransmitter onto their associated ganglion cells. Retinal Processing of Signals Stimulation of ganglion cells is actually far more complex than just described-a significant amount of signal processing occurs within the retina before action potentials actually travel to the brain. Furthermore, the retina is characterized by a large amount of convergence; many photoreceptors can synapse on each bipolar cell, and many bipolar cells synapse on a single ganglion cell. As many as 100 rod cells converge onto a single bipolar cell in peripheral regions of the retina, whereas in the fovea region only one or a few cone cells synapse onto a bipolar cell. As a result of this retinal signal processing, individual ganglion cells respond differentially to the various characteristics of visual images, such as color, intensity, form, and movement. Ganglion Cell Receptive Fields the convergence of Decreased glutamate release onto bipolar cell Decreased glutamate release onto bipolar cell Reduced inhibition by glutamate receptors; bipolar cell spontaneously depolarizes and releases more excitatory neurotransmitter Reduced excitation by glutamate receptors; bipolar cell spontaneously hyperpolarizes and releases less excitatory neurotransmitter inputs from photoreceptors and complex interconnections of cells in the retina mean that each ganglion cell carries encoded information from a particular receptive field within the retina. Receptive fields in the retina have characteristics that differ from those in the somatosensory system. If you were to shine pinpoints of light onto the retina and at the same time record from a ganglion cell, you would discover that the receptive field for that cell is round. Furthermore, the response of the ganglion cell could demonstrate either an increased or decreased action potential frequency, depending on the location of the stimulus within that single field. Because of different inputs from bipolar cell pathways to the ganglion cell, each receptive field has an inner core ("center") that responds differently than the area around it (the "surround"). As a result, a great deal of information processing takes place at this early stage of the sensory pathway. The two optic nerves meet at the base of the brain to form the optic chiasm, where some of the axons cross and travel within the optic tracts to the opposite side of the brain, providing both cerebral hemispheres with input from each eye. In either case, light striking both regions results in intermediate activation due to offsetting influences. This is an example of lateral inhibition and enhances the detection of the edges of a visual stimulus, thus increasing visual acuity. Optic chiasm both eyes open, the outer regions of our total visual field is perceived by only one eye (zones of monocular vision). The ability to compare overlapping information from the two eyes in this central region allows for depth perception and improves our ability to judge distances. Parallel processing of information continues all the way to and within the cerebral cortex to the highest stages of visual neural networks. In addition to the input from the retina, many neurons of the lateral geniculate nucleus also receive input from the brainstem reticular formation and input relayed back from the visual cortex (the primary visual area of the cerebral cortex). These nonretinal inputs can control Lateral geniculate nucleus Optic tract Occipital lobe Visual cortex (b) Visual field Binocular zone is where left and right visual fields overlap. Patient 1 has lost the right optic tract, patient 2 has lost the nerve fibers that cross at the optic chiasm, and patient 3 has lost the left occipital lobe. Draw a picture of what each person would perceive through each eye when looking at a white wall. Left visual field Right visual field Left eye Right eye Answer can be found at end of chapter. The cells of the visual pathways are organized to handle information about line, contrast, movement, and color. They do not, however, form a picture in the brain but only generate a spatial and temporal pattern of electrical activity that we perceive as a visual image. We mentioned earlier that some neurons of the visual pathway project to regions of the brain other than the visual cortex. For example, a recently discovered class of ganglion cells containing an opsinlike pigment called melanopsin carries visual information to a nucleus in the hypothalamus called the suprachiasmatic nucleus, which lies just above the optic chiasm and functions as part of the "biological clock. Other visual information passes to the brainstem and cerebellum, where it is used in the coordination of eye and head movements, fixation of gaze, and change in pupil size. For example, an object appears red because it absorbs shorter (blue) wavelengths, while simultaneously reflecting the longer (red) wavelengths. Light perceived as white is a mixture of all wavelengths, and black is the absence of all light. Color vision begins with activation of the photopigments in the cone photoreceptor cells. Human retinas have three kinds of cones-one responding optimally at long wavelengths ("L" or "red" cones), one at medium wavelengths ("M" or "green" cones), and the other stimulated best at short wavelengths ("S" or "blue" cones). Each type of cone is excited over a range of wavelengths, with the greatest response occurring near the center of that range. For example, in response to light of 531 nm wavelength, the green cones respond maximally, the red cones less, and the blue not at all. Our sensation of the shade of green at this wavelength depends upon the relative outputs of these three types of cone cells and the comparison made by higher-order cells in the visual system. In other words, they receive input from all three types of cones, and they signal not a specific color but, rather, general brightness. These latter cells are also called opponent color cells because they have an excitatory input from one type of cone receptor and an inhibitory input from another. The cell gives a weak response when stimulated with a white light because the light contains both blue and yellow wavelengths. The output from these cells is recorded by multiple, and as yet unclear, mechanisms in visual centers of the brain. Our ability to discriminate color also depends on the intensity of light striking the retina. In brightly lit conditions, the differential response of the cones allows for good color vision. Under bright lighting conditions, the three types of cones respond over different frequency ranges. Hold very still and stare at the triangle inside the yellow circle for 30 seconds. Thus, objects that appear vividly colored in bright daylight are perceived in shades of gray as night falls and lighting becomes so dim that only rods can respond. Color Blindness At high light intensities, as in daylight vision, most people-92% of the male population and over 99% of the female population- have normal color vision. However, there are several types of defects in color vision that result from mutations in the cone pigments. Color blindness results from a recessive mutation in one or more genes encoding the cone pigments. Genes encoding the red and green cone pigments are located very close to each other on the X chromosome, whereas the gene encoding the blue chromophore is located on chromosome 7. Because of this close association of the red and green genes on the X chromosome, there is a greater likelihood that genetic recombination will occur during meiosis (see Chapter 17, Section A), thus eliminating or changing the spectral characteristics of the red and green pigments proSuperior oblique removed on this side duced. In males, the presence of only a single X chromosome means that a single recessive allele from the mother will result in color blindness, even though the mother herself may have normal color vision Inferior oblique due to having one normal X chromo(transparent view) some. It also means that 50% of the male offspring of that mother will be expected to be color blind. In addition, light rays are scattered less on the way to the outer segment of those cones than in other retinal regions, because the interneuron layers and the blood vessels are displaced to the edges. To focus the most important point in the visual image (the fixation point) on the fovea and keep it there, the eyeball must be Superior oblique Lateral rectus Medial rectus Superior rectus Superior levator removed from both sides Eye Movement the macula lutea region of the retina, within which the fovea centralis is located, is specialized in several ways to provide the highest visual acuity. It is comprised of densely packed cones with minimal convergence through the bipolar and ganglion cell layers. The fast movements, called saccades, are small, jerking movements that rapidly bring the eye from one fixation point to another to allow a search of the visual field. In addition, saccades move the visual image over the receptors, thereby preventing adaptation that would result from persistent photobleaching of photoreceptors in a given region of the retina. Saccades also occur during certain periods of sleep when dreaming occurs, though these movements are not thought to be involved in "watching" the visual imagery of dreams. Slow eye movements are involved both in tracking visual objects as they move through the visual field and during compensation for movements of the head. The control centers for these compensating movements obtain their information about head movement from the vestibular system, which we will describe shortly. Control systems for the other slow movements of the eyes require the continuous feedback of visual information about the moving object. In addition, there is complex neural processing along pathways to the brain and within brain regions involved in sensing and perceiving acoustic information. Anything capable of disturbing molecules-for example, vibrating objects-can serve as a sound source. When struck, the tuning fork vibrates, creating disturbances of air molecules that make up the sound wave. The sound wave consists of zones of compression, in which the molecules are close together and the pressure is increased, alternating with zones of rarefaction, in which the molecules are farther apart and the pressure is lower. As the air molecules bump against each other, the zones of compression and rarefaction ripple outward and the sound wave is transmitted over distance. The human ear can detect volume variations over an enormous range, from the sound of someone breathing in the room to a jet taking off on a nearby runway. Because of this incredible range, sound loudness is measured in decibels (dB), which are a logarithmic function of sound pressure. The threshold for human hearing is assigned a value of 0 dB, and an increase of 30 dB, for example, would represent a 1000-fold increase in sound pressure. The sounds heard most keenly by human ears are those from sources vibrating at frequencies between 1000 and 4000 Hz, but the entire range of frequencies audible to human beings extends from 20 to 20,000 Hz. Most sounds are not pure tones but are mixtures of tones of a variety of frequencies. Sequences of pure tones of varying frequencies are generally Common Diseases of the Eye Of the many diseases of the eye, three account for a large percentage of all serious problems related to human vision, particularly as we age. The first is known as cataract, an opacity (clouding) of the lens due to the accumulation of proteins in the lens tissue. As the opacity of the lens progresses, significant blurring, loss of night vision, and difficulty focusing on nearby objects occur. Cataracts are associated with smoking, trauma, certain medications, heredity, and diseases such as diabetes. Because long-term exposure to ultraviolet radiation may also have an effect, many experts recommend wearing sunglasses to delay the onset. With the aid of an implanted artificial lens or compensating corrective lenses, effective vision can be restored. A second major cause of eye damage is glaucoma, in which retinal cells are damaged as a result of increased pressure within the eye. These two fluids are colorless and permit the transmission of light from the front of the eye to the retina. The aqueous humor is constantly formed by special vascular tissue that overlies the ciliary muscle and drains away through a canal in front of the iris at the edge of the cornea. In some instances, the aqueous humor forms faster than it is removed, which results in increased pressure within the eye. Glaucoma is a significant cause of irreversible blindness, but it can be treated either with medications that reduce the production of aqueous humor or with laser surgery that reshapes the drainage structures in the eye, thereby improving removal of aqueous humor. Its causes are in many cases unknown, but glaucoma has been linked with diabetes, certain medications, physical trauma to the eye, and genetics. In a third major disease, the macula lutea region of the retina becomes impaired in a condition known as macular degeneration, producing a defect characterized by loss of vision in the center of the visual field.

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Erythrocytes are an excellent example of the general principle of physiology that structure is a determinant of-and has coevolved with-function medicine of the prophet discount 50 mg naltrexone otc. This shape and their small size (7 mm in diameter) give the erythrocytes a high surface-area-to-volume ratio symptoms celiac disease discount naltrexone online, so that oxygen and carbon dioxide can diffuse rapidly to and from the interior of the cell symptoms viral infection discount naltrexone online visa. The site of erythrocyte production is the soft interior of certain bones called bone marrow symptoms 6 months pregnant buy naltrexone paypal, specifically symptoms liver disease buy generic naltrexone 50mg on-line, the red bone marrow medicine allergy purchase naltrexone on line. Young erythrocytes in the bone marrow still contain a few ribosomes, which produce a weblike (reticular) appearance when treated with special stains, an appearance that gives these young erythrocytes the name reticulocyte. Normally, erythrocytes lose these ribosomes about a day after leaving the bone marrow, so reticulocytes constitute only about 1% of circulating erythrocytes. In the presence of unusually rapid erythrocyte production, however, many more reticulocytes can be found in the blood; this finding can be clinically useful. Because erythrocytes lack nuclei and most organelles, they can neither reproduce themselves nor maintain their normal structure for very long. The average life span of an erythrocyte is approximately 120 days, which means that almost 1% of the erythrocytes are destroyed and must be replaced every day. Destruction of damaged or dying erythrocytes normally occurs in the spleen and the liver. The major breakdown product of hemoglobin is bilirubin, which is Erythrocytes the major function of erythrocytes is gas returned to the circulation and gives plasma its characteristic yellowish color (Chapter 15 will describe the fate of bilirubin). Several substances are necessary for the production of healthy erythrocytes, including iron, vitamins, and hormones: Iron Iron is the element to which oxygen binds on a hemoglobin molecule within an erythrocyte. Small amounts of iron are lost from the body via the urine, feces, sweat, and cells sloughed from the skin. In order to remain in iron balance, the amount of iron lost from the body must be replaced by ingestion of iron-containing foods. Particularly rich sources of iron are meat, liver, shellfish, egg yolk, beans, nuts, and cereals. A significant disruption of iron balance can result in either iron deficiency, leading to inadequate hemoglobin production, or an excess of iron in the body (hemochromatosis), which results in abnormal iron deposits and damage in various organs, including the liver, heart, pituitary gland, pancreas, and joints. The homeostatic control of iron balance resides primarily in the intestinal epithelium, which actively absorbs iron from ingested foods. The body has a considerable store of iron, mainly in the liver, bound up in a protein called ferritin. About 50% of the total body iron is in hemoglobin, 25% is in other heme-containing proteins (mainly the cytochromes) in the cells of the body, and 25% is in liver ferritin. As old erythrocytes are destroyed in the spleen (and liver), their iron is released into the plasma and bound to an iron-transport plasma protein called transferrin. Transferrin delivers almost all of this iron to the bone marrow to be incorporated into new erythrocytes. Recirculation of erythrocyte iron is very important because it involves 20 times more iron per day than the body absorbs and excretes. Folic acid and vitamin B12: Folic acid is a vitamin found in large amounts in leafy plants, yeast, and liver, is required for synthesis of the nucleotide base thymine. When this vitamin is not present in adequate amounts, impairment of cell division occurs throughout the body but is most striking in rapidly proliferating cells, including erythrocyte precursors. The production of normal erythrocyte numbers also requires extremely small quantities (one-millionth of a gram per day) of a cobalt-containing molecule, vitamin B12 (also called cobalamin), because this vitamin is required for the action of folic acid. Vitamin B12 is found only in animal products, and strictly vegetarian diets can be be deficient in it. Also, the absorption of vitamin B12 from the gastrointestinal tract requires a protein called intrinsic factor, which is secreted by the stomach (see Chapter 15). Lack of this protein, therefore, causes vitamin B12 deficiency, and the resulting erythrocyte deficiency is known as pernicious anemia. In the previous section, we stated that iron, folic acid, and vitamin B12 must be present for normal erythrocyte production, or erythropoiesis. However, none of these substances constitutes the signal that regulates the production rate. The direct control of erythropoiesis is exerted primarily by a hormone called erythropoietin, which is secreted into the blood mainly by a particular group of hormone-secreting connective tissue cells in the kidneys. Erythropoietin acts on the bone marrow to stimulate the proliferation of erythrocyte progenitor cells and their differentiation into mature erythrocytes. Erythropoietin is normally secreted in small amounts that stimulate the bone marrow to produce erythrocytes at a rate adequate to replace the usual loss. The erythropoietin secretion rate is increased markedly above basal values when there is a decreased oxygen delivery to the kidneys. Situations in which this occurs include insufficient pumping of blood by the heart, lung disease, anemia (a decrease in number of erythrocytes or in hemoglobin concentration), prolonged exercise, and exposure to high altitude. As a result of the increase in erythropoietin secretion, plasma erythropoietin concentration, erythrocyte production, and the oxygen-carrying capacity of the blood all increase. Testosterone, the male sex hormone, also stimulates the release of erythropoietin. Sickle-cell disease (formerly called sickle-cell anemia) is due to a genetic mutation that alters one amino acid in the hemoglobin chain. At the low oxygen levels existing in many capillaries (the smallest blood vessels), the abnormal hemoglobin molecules interact with each other to form fiberlike polymers that distort the erythrocyte membrane and cause the cell to form sickle shapes or other bizarre forms. This causes both the blockage of capillaries, with consequent tissue damage and pain, and the destruction of the deformed erythrocytes, with consequent anemia. Sickle-cell disease is an example of a disease that is manifested fully only in people homozygous for the mutated gene (that is, they have two copies of the mutated gene, one from each parent). In heterozygotes (one mutated copy and one normal gene), people who are said to have sickle-cell trait, the normal gene codes for normal hemoglobin and the mutated gene for the abnormal hemoglobin. The erythrocytes in this case contain both types of hemoglobin, but symptoms are observed only when the oxygen level is unusually low, as at high altitude. The persistence of the sickle-cell mutation in humans over generations is due to the fact that heterozygotes are more resistant to malaria, a blood infection caused by a protozoan parasite that is spread by mosquitoes in tropical regions. Finally, there also exist conditions in which there are more erythrocytes than normal, a condition called polycythemia. An example, to be described in Chapter 13, is the polycythemia that occurs in high-altitude dwellers. In this case, the increased number of erythrocytes is an adaptive response because it increases the oxygen-carrying capacity of blood. As discussed earlier, however, increasing the hematocrit increases the viscosity of blood. Therefore, polycythemia makes the flow of blood through blood vessels more difficult and puts a strain on the heart. Abuse of synthetic erythropoietin and the subsequent extreme polycythemia have resulted in the deaths of competitive bicyclists-one reason that such "blood doping" is banned in sports. The leukocytes are involved in immune defenses and include neutrophils, eosinophils, monocytes, macrophages, basophils, and lymphocytes. A brief description of their functions follows; these functions are detailed in Chapter 18. They are found in blood but leave capillaries and enter tissues during inflammation. After neutrophils engulf microbes such as bacteria by phagocytosis, the bacteria are destroyed within endocytotic vacuoles by proteases, oxidizing compounds, and antibacterial proteins called defensins. The production and release of neutrophils from bone marrow are greatly stimulated during the course of an infection. Eosinophils are found in the blood and in the mucosal surfaces lining the gastrointestinal, respiratory, and urinary tracts, where they fight off invasions by eukaryotic parasites. In some cases, eosinophils act by releasing toxic chemicals that kill parasites, and in other cases by phagocytosis. Monocytes are phagocytes that circulate in the blood for a short time, after which they migrate into tissues and organs and develop into macrophages. Macrophages are strategically located where they will encounter invaders, including epithelia in contact with the external environment, such as skin and the linings of respiratory and digestive tracts. They secrete an anticlotting factor called heparin at the site of an infection, which helps the circulation flush out the infected site. Basophils also secrete histamine, which attracts infection-fighting cells and proteins to the site. They protect against specific pathogens, including viruses, bacteria, toxins, and cancer cells. Some lymphocytes directly kill pathogens, and others secrete antibodies into the circulation that bind to foreign molecules and begin the process of their destruction. Regulation of Blood Cell Production In children, the marrow of most bones produces blood cells. By adulthood, however, only the bones of the chest, base of the skull, spinal vertebrae, pelvis, and ends of the limb bones remain active. The bone marrow in an adult weighs almost as much as the liver, and it produces cells at an enormous rate. Blood Flow the rapid flow of blood throughout the body is produced by pressures created by the pumping action of the heart. This type of flow is known as bulk flow because all constituents of the blood move together. The extraordinary degree of branching of blood vessels ensures that almost all cells in the body are within a few cells of at least one of the smallest branches, the capillaries. Nutrients and metabolic end products move between capillary blood and the interstitial fluid by diffusion. Movements between the interstitial fluid and the cell interior are accomplished by both diffusion and mediated transport across the plasma membrane. Platelets the circulating platelets are colorless, nonnucleated cell fragments that contain numerous granules and are much smaller than erythrocytes. Yet, it is this 5% that is performing the ultimate functions of the entire circulatory system: the supplying of nutrients, oxygen, and hormonal signals and the removal of metabolic end products and other cell products. All other components of the system serve the overall function of getting adequate blood flow through the capillaries. Circulation Pulmonary circulation Pulmonary trunk and arteries Pulmonary veins Vena cava Aorta Right atrium Left atrium Left ventricle Right ventricle Systemic circulation Systemic veins Systemic arteries Systemic arterioles, capillaries, and venules in all organs and tissues except the lungs the circulatory system forms a closed loop, so that blood pumped out of the heart through one set of vessels returns to the heart by a different set. Each half of the heart contains two chambers: an upper chamber-the atrium-and a lower chamber-the ventricle. The atrium on each side empties into the ventricle on that side, but there is usually no direct blood flow between the two atria or the two ventricles in the heart of a healthy adult. The pulmonary circulation includes blood pumped from the right ventricle through the lungs and then to the left atrium. It is then pumped through the systemic circulation from the left ventricle through all the organs and tissues of the body-except the lungs-and then to the right atrium. In both circuits, the vessels carrying blood away from the heart are called arteries; those carrying blood from body organs and tissues back toward the heart are called veins. The arteries of the systemic circulation branch off the aorta, dividing into progressively smaller vessels. The smallest arteries branch into arterioles, which branch into a huge number (estimated at 10 billion) of very small vessels, the capillaries, which unite to form larger-diameter vessels, the venules. The arterioles, capillaries, and venules are collectively termed the microcirculation. The venules in the systemic circulation then unite to form larger vessels, the veins. Blood leaves the right ventricle via a single large artery, the pulmonary trunk, which divides into the two pulmonary arteries, one supplying the right lung and the other the left. In the lungs, the arteries continue to branch and connect to arterioles, leading to capillaries that unite into venules and then veins. As depicted by the color change from blue to red, blood is oxygenated (red) as it flows through the lungs and then loses some oxygen (red to blue) as it flows through the other organs and tissues. Veins appear blue beneath the skin only because long-wavelength red light is absorbed by skin cells and subcutaneous fat, whereas short-wavelength blue light is transmitted. As blood flows through the lung capillaries, it picks up oxygen supplied to the lungs by breathing. Therefore, the blood in the pulmonary veins, left side of the heart, and systemic arteries has a high oxygen content. As this blood flows through the capillaries of peripheral tissues and organs, some of this oxygen leaves the blood to enter and be used by cells, resulting in the lower oxygen content of systemic venous and pulmonary arterial blood. This arrangement (1) guarantees that systemic tissues receive freshly oxygenated blood and (2) allows for independent variation in blood flow through different tissues as their metabolic activities change. Finally, there are some exceptions to the usual anatomical pattern described in this section for the systemic circulation-for Organ Brain Heart Skeletal muscle Skin Kidneys Flow at rest (mL/min) 650 (13%) 215 (4%) 1030 (20%) example, the liver and the anterior pituitary gland. In those organs, blood passes through two capillary beds, arranged in series and connected by veins, before returning to the heart. As applied to blood, these factors are collectively referred to as hemodynamics, and they demonstrate the general principle of physiology that physiological processes are dictated by the laws of chemistry and physics. In all parts of the system, blood flow (F) is always from a region of higher pressure to one of lower pressure. The pressure exerted by any fluid is called a hydrostatic pressure, but this is usually shortened simply to "pressure" in descriptions of the circulatory system, and it denotes the force exerted by the blood. This force is generated in the blood by the contraction of the heart, and its magnitude varies throughout the system for reasons that will be described later. The units for the rate of flow are volume per unit time, usually liters per minute (L/min).

A fascinating view inside real human bodies that also incorporates animations to help you understand gastrointestinal physiology medicine balls for sale order naltrexone cheap. This chapter deals with two topics that are concerned in one way or another with those same concepts-but for the entire body treatment 4 ringworm naltrexone 50 mg free shipping. First symptoms estrogen dominance purchase naltrexone 50 mg without a prescription, this chapter describes how the metabolic pathways for carbohydrate treatment thesaurus discount naltrexone 50mg with visa, fat medications that cause high blood pressure naltrexone 50 mg sale, and protein are integrated and controlled so as to provide continuous sources of energy to the various tissues and organs symptoms of hiv buy genuine naltrexone online, even during periods of fasting. Next, the factors that determine total-body energy balance and the regulation of body temperature are described. In Section A, you will learn how the control of metabolism is a good example of the general principle of physiology that most physiological functions are controlled by multiple regulatory systems, often working in opposition. This will be particularly evident by the opposing effects of the primary regulatory hormone insulin and the counterregulatory hormones cortisol, growth hormone, glucagon, and epinephrine on the balance of glucose and other energy sources in the blood. The control of metabolism and energy balance also illustrates the general principles of physiology that homeostasis is essential for health and survival and that physiological processes require the transfer and balance of matter and energy. This section will also illustrate how physiological processes are dictated by the laws of chemistry and physics, particularly in relation to heat transfer between the body and the environment. Recall from Chapter 15 that carbohydrates and proteins are absorbed primarily as monosaccharides and amino acids, respectively, into the blood leaving the gastrointestinal tract. In contrast to monosaccharides and amino acids, fat is absorbed into the lymph in chylomicrons, which are too large to enter capillaries. It is not surprising, therefore, that mechanisms have evolved for survival during alternating periods of food availability and fasting. Because an average meal requires approximately 4 h for complete absorption, our usual three-meal-a-day pattern places us in the postabsorptive state during the late morning, again in the late afternoon, and during most of the night. Total-body energy stores are adequate for the average person to withstand a fast of many weeks, provided water is available. All tissues Protein Amino acids Absorbed Carbohydrate Some of the carbohydrates absorbed from the gastrointestinal tract are galactose and fructose. Because these sugars are either converted to glucose by the liver or enter essentially the same metabolic pathways as glucose, we will for simplicity refer to absorbed carbohydrates as glucose. Skeletal muscle makes up the majority of body mass, so it is the major consumer of glucose, even at rest. The arrow from amino acids to protein is dashed to denote the fact that excess amino acids are not stored as protein (see text). Regulation of Organic Metabolism and Energy Balance 565 catabolizes glucose during the absorptive state but also converts some of the glucose to the polysaccharide glycogen, which is then stored in muscle cells for future use. Adipose-tissue cells (adipocytes) also catabolize glucose for energy, but the most important fate of glucose in adipocytes during the absorptive state is its transformation to fat (triglycerides). Glucose is the precursor of both glycerol 3-phosphate and fatty acids, and these molecules are then linked together to form triglycerides, which are stored in the cell. This is a very important point: During the absorptive state, there is net uptake of glucose by the liver. It is either stored as glycogen, as in skeletal muscle, or transformed to glycerol 3-phosphate and fatty acids, which are then used to synthesize triglycerides, as in adipose tissue. Most of the fat synthesized from glucose in the liver is packaged along with specific proteins into molecular aggregates of lipids and proteins that belong to the general class of particles known as lipoproteins. Instead, their triglycerides are hydrolyzed mainly to monoglycerides (glycerol linked to one fatty acid) and fatty acids by the enzyme lipoprotein lipase. This enzyme is located on the blood-facing surface of capillary endothelial cells, especially those in adipose tissue. In adipose-tissue capillaries, the fatty acids generated by the action of lipoprotein lipase diffuse from the capillaries into the adipocytes. There, they combine with glycerol 3-phosphate, supplied by glucose metabolites, to form triglycerides once again. Some of the monoglycerides formed in the blood by the action of lipoprotein lipase in adipose-tissue capillaries are also taken up by adipocytes, where enzymes can reattach fatty acids to the two available carbon atoms of the monoglyceride and thereby form a triglyceride. In addition, some of the monoglycerides travel via the blood to the liver, where they are metabolized. To summarize, the major fates of glucose during the absorptive phase are (1) utilization for energy, (2) storage as glycogen in liver and skeletal muscle, and (3) storage as fat in adipose tissue. Absorbed Lipids As described in Chapter 15, many of the absorbed lipids are packaged into chylomicrons that enter the lymph and, from there, the circulation. The fatty acids of plasma chylomicrons are released, mainly within adipose-tissue capillaries, by the action of endothelial lipoprotein lipase. The released fatty acids then diffuse into adipocytes and combine with glycerol 3-phosphate, synthesized in the adipocytes from glucose metabolites, to form triglycerides. The importance of glucose for triglyceride synthesis in adipocytes cannot be overemphasized. As we have seen, sources (2) and (3) require the action of lipoprotein lipase to release the fatty acids from the circulating triglycerides. The relative amounts of carbohydrate and fat used for energy during the absorptive state depend largely on the content of the meal. One very important absorbed lipid found in chylomicrons- cholesterol-does not serve as a metabolic energy source but instead is a component of plasma membranes and a precursor for bile salts and steroid hormones. Despite its importance, however, cholesterol in excess can also contribute to disease. Specifically, high plasma concentrations of cholesterol enhance the development of atherosclerosis, the arterial thickening that may lead to heart attacks, strokes, and other forms of cardiovascular damage (Chapter 12). The control of cholesterol balance in the body provides an opportunity to illustrate the importance of the general principle of physiology that homeostasis is essential for health and survival. The two sources of cholesterol are dietary cholesterol and cholesterol synthesized within the body. Dietary cholesterol comes from animal sources, egg yolk being by far the richest in this lipid (a single large egg contains about 185 mg of cholesterol). Not all ingested cholesterol is absorbed into the blood, however; some simply passes through the length of the gastrointestinal tract and is excreted in the feces. In addition to using ingested cholesterol, almost all cells can synthesize some of the cholesterol required for their own plasma membranes, but most cannot do so in adequate amounts and depend upon receiving cholesterol from the blood. This is also true of the endocrine cells that produce steroid hormones from cholesterol. In contrast, the liver and small intestine can produce large amounts of cholesterol, most of which enters the blood for use elsewhere. Now we look at the other side of cholesterol balance-the pathways, all involving the liver, for net cholesterol loss from the body. First, some plasma cholesterol is taken up by liver cells and secreted into the bile, which carries it to the gallbladder and from there to the lumen of the small intestine. Here, it is treated much like ingested cholesterol, some being absorbed back into the blood and the remainder excreted in the feces. Most of the cholesterol that is converted to bile salts, stored in the gallbladder, and secreted into the intestine gets recycled back to the liver. Changes in dietary cholesterol can modify plasma cholesterol concentration, but not usually dramatically. Cholesterol synthesis by the liver is up-regulated when dietary cholesterol is decreased, and vice versa. After their production by the liver, these bile salts, like secreted cholesterol, eventually flow through the bile duct into the small intestine. The homeostatic control mechanisms that keep plasma cholesterol concentrations within a normal range operate on all of these hepatic processes, but the single most important response involves cholesterol synthesis. Thus, as soon as the plasma cholesterol concentration increases because of cholesterol ingestion, hepatic synthesis of cholesterol is inhibited and the plasma concentration of cholesterol remains close to its original value. Conversely, when dietary cholesterol is reduced and plasma cholesterol decreases, hepatic synthesis is stimulated (released from inhibition). The sensitivity of this negative feedback control of cholesterol synthesis differs greatly from person to person, but it is the major reason why, for most people, it is difficult to decrease plasma cholesterol concentration very much by altering only dietary cholesterol. The story is more complicated than this, however, because not all plasma cholesterol has the same function or significance for disease. Like most other lipids, cholesterol circulates in the plasma as part of various lipoprotein complexes. They then deliver this cholesterol to the liver, which secretes it into the bile or converts it to bile salts. After menopause, the cholesterol values and coronary artery disease rates in women not on estrogen-replacement therapy become similar to those in men. If untreated, this disease may result in atherosclerosis and heart disease at unusually young ages. Postabsorptive State As the absorptive state ends, net synthesis of glycogen, triglycerides, and protein ceases and net catabolism of all these substances begins. The overall significance of these events can be understood in terms of the essential problem during the postabsorptive state: No glucose is being absorbed from the gastrointestinal tract, yet the plasma glucose concentration must be homeostatically maintained because the central nervous system normally utilizes only glucose for energy. If the plasma glucose concentration decreases too much, alterations of neural activity occur, ranging from subtle impairment of mental function to seizures, coma, and even death. Like cholesterol, the control of glucose balance is another classic example of the general principle of physiology that homeostasis is essential for health and survival. The events that maintain plasma glucose concentration fall into two categories: (1) reactions that provide sources of blood glucose; and (2) cellular utilization of fat for energy, thereby "sparing" glucose. Absorbed Amino Acids Some amino acids are absorbed into liver cells and used to synthesize a variety of proteins, including liver enzymes and plasma proteins, or they are converted to carbohydrate-like intermediates known as a-keto acids by removal of the amino group. The amino groups are used to synthesize urea in the liver, which enters the blood and is excreted by the kidneys. They can also be used to synthesize fatty acids, thereby participating in fat synthesis by the liver. All cells require a constant supply of amino acids for protein synthesis and participate in protein metabolism. In other words, excess amino acids are not stored as protein in the sense that glucose is stored as glycogen or that both glucose and fat are stored as triglycerides. Rather, ingested amino acids in excess of those required to maintain a stable rate of protein turnover are converted to carbohydrate or triglycerides. Therefore, eating large amounts of protein does not in itself cause increases in total-body protein. Increased daily consumption of protein does, however, provide the amino acids required to support the high rates of protein synthesis occurring in growing children or in adults who increase muscle mass by engaging in weight-bearing exercises. Glycogenolysis, the hydrolysis of glycogen stores to monomers of glucose 6-phosphate, occurs in the liver. Glucose 6-phosphate is then enzymatically converted to glucose, which then enters the blood. Hepatic glycogenolysis begins within seconds of an appropriate stimulus, such as sympathetic nervous system activation. As a result, it is the first line of defense in maintaining the plasma glucose concentration within a homeostatic range. Glycogenolysis also occurs in skeletal muscle, which contains approximately the same amount of glycogen as the liver. Unlike the liver, however, muscle cells lack the enzyme necessary to form glucose from the glucose 6-phosphate formed during glycogenolysis; therefore, muscle glycogen is not a source of blood glucose. Some of the lactate, however, enters the blood, circulates to the liver, and is used to synthesize glucose, which can then leave the liver cells to enter the blood. The catabolism of triglycerides in adipose tissue yields glycerol and fatty acids, a process termed lipolysis. Thus, an important source of glucose during the postabsorptive state is the glycerol released when adiposetissue triglyceride is broken down. A few hours into the postabsorptive state, protein becomes another source of blood glucose. Large quantities of protein in muscle and other tissues can be catabolized without serious cellular malfunction. Some carbohydrate is stored as glycogen in liver and muscle, but most carbohydrates and fats in excess of that used for energy are stored as fat in adipose tissue. The remaining amino acids in dietary protein are used for energy or converted to fat. How is this principle apparent in the metabolic events of the postabsorptive state Before this point is reached, however, protein breakdown can supply large quantities of amino acids. These amino acids enter the blood and are taken up by the liver, where some can be metabolized via the a-keto acid pathway to glucose. Synthesis of glucose from such precursors as amino acids and glycerol is known as gluconeogenesis-that is, "creation of new glucose. Although historically this process was considered to be almost entirely carried out by the liver with a small contribution by the kidneys, recent evidence strongly suggests that the kidneys contribute much more to gluconeogenesis than previously believed. Glucose Sparing (Fat Utilization) the approximately 180 g of glucose per day produced by gluconeogenesis in the liver (and kidneys) during fasting supplies about 720 kcal of energy. As described later in this chapter, typical total energy expenditure for an average adult is 1500 to 3000 kcal/day. Therefore, gluconeogenesis cannot supply all the energy demands of the body during fasting. An adjustment must therefore take place during the transition from the absorptive to the postabsorptive state. Most organs and tissues, other than those of the nervous system, significantly decrease their glucose catabolism and increase their fat utilization, the latter becoming the major energy source. This metabolic adjustment, known as glucose sparing, "spares" the glucose produced by the liver for use by the nervous system. The essential step in this adjustment is lipolysis, the catabolism of adipose-tissue triglyceride, which liberates glycerol and fatty acids into the blood.