Dr Luigi Camporota

• Specialist Registrar in Intensive Care Medicine
• Department of Adult Intensive Care
• Guy? and St Thomas?NHS Foundation Trust
• London, UK

List the general categories of intercellular messengers and briefly describe how they differ symptoms of strep throat buy generic flexeril 15mg online. However symptoms queasy stomach purchase 15mg flexeril with visa, as you likely know from personal experience 911 treatment center discount flexeril 15mg online, evaporation of water from the body is less effective in humid environments medicine kit order generic flexeril from india, which makes it more dangerous to exercise when it is not only hot but also humid medicine 44 159 generic flexeril 15 mg online. The sources of perspiration are the sweat glands treatment 5ths disease buy flexeril on line amex, which are located beneath the skin and which secrete a salty solution through ducts to the surface of the skin. Consequently, the profuse sweating that initially occurred in this man caused his extracellular fluid levels to decrease. In fact, the fluid levels decreased so severely that the amount of blood available to be pumped out of his heart with each heartbeat also decreased. The relationship between fluid volume and blood pressure is an important one that you will learn about in detail in Chapter 12. Generally speaking, if extracellular fluid levels decrease, blood pressure decreases as a consequence. This explains why our subject felt light-headed, particularly when he tried to stand up too quickly. As his blood pressure decreased, the ability of his heart to pump sufficient blood against gravity up to his brain also decreased; when brain cells are deprived of blood flow, they begin to malfunction. Perhaps you have occasionally experienced a little of this light-headed feeling when you have jumped out of a chair or bed and stood up too quickly. Normally, your nervous system quickly compensates for the effects of gravity on blood flowing up to the brain, as will be described in Chapters 6 and 12. In a person with decreased blood volume and pressure, however, this compensation may not happen and the person can lose consciousness. If you have ever tasted the sweat on your upper lip on a hot day, you know that it is somewhat salty. That is because sweat is derived from extracellular fluid, which as you have learned is a watery solution of ions (derived from salts, such as NaCl) and other substances. Sweat, however, is slightly more dilute than extracellular fluid because more water than ions is secreted from sweat glands. Consequently, the more heavily one perspires, the more concentrated the extracellular fluid becomes. In other words, the total amount of water and ions in the extracellular fluid decreases with perspiration, but the remaining fluid is "saltier. A homeostatic balance of ion concentrations in the body fluids is absolutely essential for normal heart and brain function, as you will learn in Chapters 4 and 6. Throughout this text, you will find a feature at the end of each chapter called the "Clinical Case Study. The clinical case studies will increase in complexity as you progress through the text and will enable you to integrate recent material from a given chapter with information learned in previous chapters. In this first clinical case study, we examine a serious and potentially lifethreatening condition that can occur in individuals in whom body temperature homeostasis is disrupted. All of the material presented in this clinical case study will be explored in depth in subsequent chapters, as you learn the mechanisms that underlie the pathologies and compensatory responses illustrated here in brief. Notice as you read that the first two general principles of physiology described earlier are particularly relevant to this case. It is highly recommended that you return to this case study as a benchmark at the end of your semester; we are certain that you will be amazed at how your understanding of physiology has grown in that time. A 64-year-old, fair-skinned man in good overall health spent a very hot, humid summer day gardening in his backyard. After several hours in the sun, he began to feel light-headed and confused as he knelt over his vegetable garden. Although earlier he had been perspiring profusely and appeared flushed, his sweating had eventually stopped. Because he also felt confused and disoriented, he could not recall for how long he had not been perspiring, or even how long it had been since he had taken a drink of water. He called to his wife, who was alarmed to see that his skin had since turned a pale-blue color. She asked her husband to come indoors, but he fainted as soon as he tried to stand. The wife called for an ambulance, and the man was taken to a hospital and diagnosed with a condition called heatstroke. Based on that, what would you expect to occur to skin blood vessels when a person first starts feeling warm As you learned in this chapter, body temperature is a physiological function that is under homeostatic control. Conversely, as in our example here, if body temperature increases, heat production decreases and heat loss increases. When our patient began gardening on a hot, humid day, his body temperature began to increase. At first, the blood vessels in his skin dilated, making him appear flushed and helping him dissipate heat across his skin. To understand this, we must consider that several homeostatic variables were disrupted by his activities. As the sweating continued, it resulted in decreased fluid levels and a negative balance of key ion concentrations in his body; this contributed to a decrease in mental function, and he became confused. As his body fluid levels continued to decrease, his blood pressure also decreased, further endangering brain function. Though it is potentially life threatening for body temperature to increase too much, it is also life threatening for blood pressure to decrease too much. Eventually, many of the blood vessels in regions of the body that are not immediately required for survival, such as the skin, began to constrict, or close off. By doing so, the more vital organs of the body-such as the brain-could receive sufficient blood. It also made it more difficult for sweat glands in the skin to obtain the fluid required to produce sweat. The man gradually decreased perspiring and eventually stopped sweating altogether. This case illustrates a critical feature of homeostasis that you will encounter throughout this textbook and that was emphasized in this chapter. Often, when one physiological variable such as body temperature is disrupted, the compensatory responses initiated to correct that disruption cause, in turn, imbalances in other variables. These secondary imbalances must also be compensated for, and the significance of each imbalance must be "weighed" against the others. In this example, the man was treated with intravenous fluids made up of a salt solution to restore his fluid levels and concentrations, and he was immersed in a cool bath and given cool compresses to help reduce his body temperature. Although he recovered, many people do not survive heatstroke because of its profound impact on homeostasis. Efferent pathways carry information away from the integrating center of a reflex arc. In a reflex arc initiated by touching a hand to a hot stove, the effector belongs to which class of tissue The type of tissue involved in many types of transport processes, and which often lines the inner surfaces of tubular structures, is called. Physiological changes that occur in anticipation of a future change to a homeostatic variable are called processes. A is a chemical factor released by cells that acts on neighboring cells without having to first enter the blood. When loss of a substance from the body exceeds its gain, a person is said to be in balance for that substance. The Inuit of Alaska and Canada have a remarkable ability to work in the cold without gloves and not suffer decreased skin blood flow. Does this prove that there is a genetic difference between the Inuit and other people with regard to this characteristic Explain how an imbalance in any given physiological variable may produce a change in one or more other variables. For example, shivering would not occur (muscles may even become more relaxed than usual), and blood vessels in the skin would not constrict. Indeed, in such a scenario, skin blood vessels would dilate to bring warm blood to the skin surface, where the heat could leave the body across the skin. This personalized adaptive learning tool serves as a guide to your reading by helping you discover which aspects of homeostasis you have mastered, and which will require more attention. A fascinating view inside real human bodies that also incorporates animations to help you understand homeostasis, the central idea of physiology. To fully appreciate the mechanisms by which homeostasis is achieved, we must first understand the basic chemistry of the human body, including the key features of atoms and molecules that contribute to their ability to interact with one another. Such interactions form the basis for processes as diverse as maintaining a healthy pH of the body fluids, determining which molecules will bind to or otherwise influence the function of other molecules, forming functional proteins that mediate numerous physiological processes, and maintaining energy homeostasis. In this chapter, we also describe the distinguishing characteristics of some of the major organic molecules in the human body. The specific functions of these molecules in physiology will be introduced here and discussed more fully in subsequent chapters where appropriate. This chapter will provide you with the knowledge required to best appreciate the significance of one of the general principles of physiology introduced in Chapter 1, namely that physiological processes are dictated by the laws of chemistry and physics. Each type of atom-carbon, hydrogen, oxygen, and so on- is called a chemical element. A one- or two-letter symbol is used as an abbreviated identification for each element. Although more than 100 elements occur naturally or have been synthesized in the laboratory, only 24 (Table 2. Components of Atoms the chemical properties of atoms can be described in terms of three subatomic particles-protons, neutrons, and electrons. The larger the atom, the more electrons it contains, and therefore the more orbitals that exist around the nucleus. Orbitals are found in regions known as electron shells; additional shells exist at greater and greater distances from the nucleus as atoms get bigger. An atom such as carbon has more shells than does hydrogen with its lone electron, but fewer than an atom such as iron, which has a greater number of electrons. The second shell can hold up to eight electrons; the first two electrons fill a spherical orbital, and subsequent electrons fill three additional, propeller-shaped ("p") orbitals. Additional shells can accommodate further orbitals; this will happen once the inner shells are filled. First electron shell is filled with two electrons s orbital of second electron shell is filled with two electrons Major Elements: 99. Up to two electrons may occupy an orbital, shown here as regions in which an electron is likely to be found. The orbitals exist within electron shells at progressively greater distances from the nucleus as atoms get bigger. Chemical Composition of the Body and Its Relation to Physiology 21 An atom is most stable when all of the orbitals in its outermost shell are filled with two electrons each. If one or more orbitals do not have their capacity of electrons, the atom can react with other atoms and form molecules, as described later. For many of the atoms that are most important for physiology, the outer shell requires eight electrons in its orbitals in order to be filled to capacity. Protons have one unit of positive charge, electrons have one unit of negative charge, and neutrons are electrically neutral. Because the protons are located in the atomic nucleus, the nucleus has a net positive charge equal to the number of protons it contains. One of the fundamental principles of physics is that opposite electrical charges attract each other and like charges repel each other. It is the attraction between the positively charged protons and the negatively charged electrons that serves as a major force that forms an atom. The entire atom has no net electrical charge, however, because the number of negatively charged electrons orbiting the nucleus equals the number of positively charged protons in the nucleus. Atomic Number Each chemical element contains a unique and specific number of protons, and it is this number, known as the atomic number, that distinguishes one type of atom from another. For example, hydrogen, the simplest atom, has an atomic number of 1, corresponding to its single proton. As another example, calcium has an atomic number of 20, corresponding to its 20 protons. Because an atom is electrically neutral, the atomic number is also equal to the number of electrons in the atom. In one example, high-energy radiation can be focused onto cancerous areas of the body to kill cancer cells. In one common method, the sugar glucose can be chemically modified so that it contains a radioactive isotope of fluorine. When injected into the blood, the cells of all of the organs of the body take up the radioactive glucose just as they would ordinary glucose. The gram atomic mass of a chemical element is the amount of the element, in grams, equal to the numerical value of its atomic mass. Thus, 12 g of carbon (assuming it is all 12C) is 1 gram Atomic Mass Atoms have very little mass. By convention, this scale is based upon assigning the carbon atom a mass of exactly 12. On this scale, a hydrogen atom has an atomic mass of approximately 1, indicating that it has one-twelfth the mass of a carbon atom. Although the number of neutrons in the nucleus of an atom is often equal to the number of protons, many chemical elements can exist in multiple forms, called isotopes, which have identical numbers of protons but which differ in the number of neutrons they contain.

The lateral geniculate body (part of the visual pathway) project s to the visual cortex medicine 2015 song purchase flexeril online now, while the m edial geniculate body (part of the auditory pathway) project s to the auditory cortex medications you cant donate blood order 15 mg flexeril visa. The lateral nuclei consist of the lateral dorsal nucleus and lateral posterior nucleus medications vascular dementia generic flexeril 15mg. They represent the dorsal portion of the ventrolateral group and receive their input from other thalam ic nuclei (hence the term "integration nuclei treatment gastritis cheap 15mg flexeril otc," see p asthma medications 7 letters generic 15mg flexeril amex. D Synopsis of some clinically important connections of the speci c thalamic nuclei the speci c thalam ic nuclei project to the cerebral cortex medications metabolized by cyp2d6 discount 15mg flexeril visa. The table below lists the origins of the tracts that term inate in the nuclei, the nuclei them selves, and the sites to which their a erent bers project. The hypothalam us is the lowest level of the diencephalon, situated below the thalam us. The hypothalam us is a sm all nuclear complex located ventral to the thalam us and separated from it by the hypothalam ic sulcus. Despite its sm all size, the hypothalam us is the com m and center for all autonom ic functions in the body. The Term inologia Anatom ica lists over 30 hypothalam ic nuclei located in the lateral wall and oor of the third ventricle. Only a few of the larger, m ore clinically important nuclei are m entioned in this unit. The coronal section (c) shows the further subdivision of the hypothalam us by the fornix into lateral and m edial zones. The three nuclear groups described above are part of the medial zone, whereas the nuclei in the lateral zone are not subdivided into speci c groups. Bilateral lesions of the m am m illary bodies and their nuclei are m anifested by the K orsako syndrome, which is frequently associated with alcoholism (cause: vitam in B1 [thiam ine] de ciency). A m ajor neuropathological nding is the presence of hem orrhages in the m am m illary bodies, which are sectioned at autopsy to con rm the diagnosis. Diencepha lon Stria term inalis Fornix To reticular form ation Mam m illothalam ic fasciculus Stria m edullaris thalam i Posterior nucleus Medial forebrain bundle Preoptic nucleus Supraoptic nucleus Amygdala Paraventricular nucleus Supraoptic nucleus Tuberohypophyseal tract Hypothalam ichypophyseal tract Posterior lobe of pituitary gland a Hippocam pus Mam m illary body Peduncle of mam m illary body b Retroflex tract Mam m illotegm ental tract Dorsal longitudinal fasciculus C Important a erent and e erent connections of the hypothalamus Midsaggital section of the right hem isphere viewed from the m edial side. Because the hypothalam us coordinates all the autonom ic functions in the body, it establishes a erent (blue) and e erent (red) connections with m any brain regions. The bers of this tract m ediate the exchange of autonom ic inform ation bet ween the hypothalam us, cranial nerve nuclei, and spinal cord. D Functions of the hypothalamus the hypothalam us is the coordinating center of the autonom ic nervous system. Certain functions can be assigned to speci c regions or nuclei in the hypothalam us, and these relationships are outlined in the table. Region or nucleus Function Anterior preoptic region Maintains constant body temperature; Lesion: central hypothermia Responds to temperature changes. While the posterior pituitary lobe is an extension of the diencephalon, the anterior pituitary lobe is derived from the epithelium of the roof of the pharynx. The pituitary stalk (infundibulum) at taches both lobes of the gland to the hypothalam us. Pituitary horm ones are not synthesized in the posterior pituitary lobe (neurohypophysis) but in neurons located in the paraventricular nucleus and supraoptic nucleus of the hypothalam us. They are then transported by axons of the hypothalam ic-hypophyseal tract to the neurohypophysis, where they are released as needed. The peptide horm ones are stored in vesicles (aggregated into large "Herring bodies") in the cell bodies of the neurosecretory neurons and are carried to the posterior lobe by anterograde axoplasm ic transport. Diencepha lon Dorsom edial nucleus C Hypophyseal portal circulation and connections of the hypothalamic nuclei to the anterior pituitary lobe the superior hypophyseal arteries from each side of the body form a vascular plexus around the infundibulum (pituitary stalk). The axons from neurons of the hypothalam ic nuclei (dark red and dark blue arrows) term inate at this plexus and secrete horm ones that have been produced in sm aller (parvocellular) neurons of the hypothalam us. Ventrom edial nucleus Superior hypophyseal artery Tuberoinfundibular tract Inferior hypophyseal artery Capillary Chrom ophobic cells Basophilic cells Acidophilic cells D Histology of the anterior pituitary gland Three t ypes of cells can be distinguished in the anterior pituitary gland using classic histologic m ethods: acidophilic cells, basophilic cells, and chrom ophobic cells. The lat ter have already released their horm ones, and are therefore negative in im m unohistochem ical tests that speci cally detect peptide horm ones; they are not listed in E. The acidophilic (a) cells secrete horm ones that act directly on target cells (non-glandotropic horm ones) while the basophilic (b) cells stim ulate subordinate endocrine cells (glandotropic horm ones). The appropriateness of the term "epithalam us" can be appreciated in this plane of section, which shows the epithalam us riding upon the thalam us (epi = "upon"). The subthalam us contains nuclei of the m edial m otor system (m otor zones of the diencephalon), and has connections with the m otor nuclei of the tegm entum. In fact, the subthalam us can be considered the cranial extension of the tegm entum. It is connected to the diencephalon by the habenula, which contains both a erent and e erent tract s. Its topographical relationship to the third ventricle is seen particularly well in m idsagit tal section (pineal recess). In reptiles, the calvaria over the pineal gland is thinned so that it is receptive to light stim uli. This is not the case in hum ans, although retinal afferent s still com m unicate with the pineal through relay stations in the hypothalam us and the superior cervical (sym pathetic) ganglion, helping to regulate circadian rhythm s. Calci cations (corpora arenacea, "brain sand") are frequently present and m ay be visible on radiographs; they have no pathological signi cance. The pinealocytes produce melatonin, which plays a role in the regulation of circadian rhythm s; it m ay be taken prophylactically, for example, to m oderate the e ects of jet lag. If the pineal ceases to function during childhood, the individual m ay undergo precocious pubert y given that the pineal has signi cant, m ostly inhibitory, e ects on various endocrine system s. Diencepha lon Fornix Habenulointerpeduncular tract Septal nucleus Preoptic region Anterior perforated substance (olfactory area) Interpeduncular nucleus Amygdala Stria term inalis Stria m edullaris of thalam us Habenula Pineal gland Habenulotectal tract Quadrigem inal plate Habenulotegm ental tract Dorsal tegm ental nucleus D Habenular nuclei and their ber connections Midsagit tal section of the right hem isphere viewed from the m edial side. The habenula ("reins") and their nuclei function as a relay station for a erent olfactory impulses. After their relay in the habenular nuclei, their e erent bers are distributed to the salivatory and m otor nuclei (m astication) in the brainstem. A erent connections (blue): A erent im pulses from the anterior perforated substance (olfactory area), septal nuclei, and preoptic region are transm it ted by the stria m edullaris to the habenular nuclei. Certain sm all nuclei are exempt from this m igration and rem ain near the m idline: these are the zona incerta and subthalamic nucleus. The subthalam ic nucleus, substantia nigra, and putam en send a erent bers to the globus pallidus. The globus pallidus in turn distributes e erent bers to these regions and also to the thalam us through a tract called the lenticular fasciculus. Compared to the telencephalon, the brainstem is so sm all that it s part s becom e visible only in m idsagit tal section (b). The purely topographical dem arkation of zones in the brainstem from cranial to caudal is based on its external, m acroscopic structure. The mesencephalon begins im m ediately at the diencephalon and extends to the cranial transverse gyrus of the pons which at its caudal end is separated from the m edulla oblongata by the bulbopontine sulcus. The brainstem extends to the point of exit of the rst spinal nerve after which the spinal cord begins. Also purely topographical criteria are used to subdivide each brainstem section into four parts (see B). All com m unication bet ween the spinal cord and the m ore rostral regions of the brain diencephalon passes though these tract s within the brainstem. Depending on the ow of inform ation, a distinction is drawn bet ween ascending (a erent, to the telencephalon) and descending (e erent, away from the telencephalon) tract s. Note: Since so m any nuclei and tracts lie so closely together in the brainstem, even sm all lesions, for example, in case of bleeding brainstem stroke can cause severe dam age. Cranial to the pons lie the crus cerebri, which contain descending m otor pathways. A part of these bers extend to the pyram ids of the the m edulla oblongata and m ost of them cross over in the pyram idal decussation. The olive, located lateral to the pyram id, contains a large m otor nuclear group, the olivary nuclei. What is striking is the view of the diam ond-shaped fourth ventricle, the oor of which is outlined by several cranial nerve nuclei. The superior colliculi are integrative centers related to visual inform ation and the inferior colliculi are relay stations of the auditory pathway. The brachium ("arm ") of the superior colliculus and the brachium of the inferior colliculus connect these colliculi with their corresponding thalam ic nuclei. Lateral to the fourth ventricle, as a topographic connection between cerebellum and brainstem, are three paired cerebellar peduncles: the superior, m iddle, and inferior cerebellar peduncles. Very clearly displayed in this view is the fact that the ventral curvature of the pons extends into the m iddle cerebellar peduncle, which connects the pons with the cerebellum. The diagram s show the nuclei them selves and the course of the nerves (to save space, the vestibular and cochlear nuclei are not shown). The arrangem ent of the cranial nerve nuclei is easier to understand when we divide them into functional nuclear colum ns. The arrangem ent of these nuclei can be derived from the arrangem ent of the nuclei in the spinal cord (see p. The function and connections of som e of these cranial nerves can be clinically evaluated by testing the brainstem re exes (whose relay centers are located in the brainstem). Bra instem Pallidum C Location of the substantia nig ra and red nucleus in the mesencephalon Both of these nuclei, like the cranial nerve nuclei, are well-de ned structures that belong functionally to the extrapyramidal motor system. Anatom ically, the substantia nigra is part of the cerebral peduncles and therefore is not located in the tegm entum of the m esencephalon (see A, p. Owing to their high respective content s of m elanin and iron, the substantia nigra and red nucleus appear brown and red, respectively, in sections of fresh brain tissue. Both nuclei extend into the diencephalon and are connected to it s nuclei by ber tracts (see E). A feature com mon to all three sections is the dorsally situated tegm entum ("hood," medium gray), the phylogenetically old part of the brainstem. Anterior to the tegmentum are the large ascending and descending tracts that run to and from the telencephalon. This region is called the cerebral peduncle (crus cerebri) in the mesencephalon, the basilar part (base) of the pons at the pontine level, and the pyramids in the medulla oblongata. The tegmentum is covered dorsally by the tectum (= "roof") only in the region of the mesencephalon. In the mature brain pictured here, this structure forms the quadrigeminal plate containing the superior and inferior colliculi ("lit tle hills"), shown faintly in Da. The brainstem is covered by the cerebellum at the level of the medulla oblongata and pons and therefore lacks a tectal covering at those levels. E A erent (blue) and e erent (red) connections of the red nucleus and substantia nigra these t wo nuclei are important relay stations in the m otor system. It receives a erent axons from the dentate nucleus (dentatorubral tract), superior colliculi (tectorubral tract), inner pallidum (pallidorubral tract), and cerebral cortex (corticorubral tract). The red nucleus sends its axons to the olive (rubro-olivary bers and reticulo-olivary bers, part of the central tegm ental tract) and to the spinal cord (rubrospinal tract). A lesion of the red nucleus produces resting trem or, abnorm al m uscle tone (tested as involuntary m uscular resistance of the joints in the relaxed patient), and choreoathetosis (involuntary writhing m ovem ents, usually involving the distal parts of the lim bs). The substantia nig ra consist s of a compact part (dark, contains m elanin) and a reticular part (reddish, contains iron; for sim plicit y, the entire substantia nigra appears dark in the drawing). Most of its axons project di usely to other brain areas and are not collected into tract s. Som e axons from the caudate nucleus and putam en (striatonigral bers), and precentral cortex (corticonigral bers) term inate in the substantia nigra. The morphological term "reticular formation" incorrectly im plies a hom ogeneit y when in fact it represent s di erent centers. Thus, it would be bet ter to refer to them as reticular nuclei, which m orpologically are di cult to distinguish from one another. The reticular nuclei use di erent neurotransm it ters to serve their di erent functions. Locus coeruleus Median raphe nucleus Pontine raphe nucleus Trigem inal m otor nucleus Nucleus of abducent nerve Facial nucleus Pneumotaxic region Raphe nucleus magnus Raphe nucleus obscurus Nucleus ambiguus Nucleus of oculomotor nerve Nuclear region for visual orientation in space, autonom ic center for coordinating food intake C Cyto - and transmitter architectonics Dorsal view of the brainstem after the cerebellum has been rem oved; left hem isphere: Cytoarchitectonics; right hem isphere: transm it ter architectonics.

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Furthermore treatment 5th disease discount 15 mg flexeril, the pattern of injury and degree of displacement are less significant for poor outcome than the quality of the reduction or the extent of soft tissue injury to the foot symptoms 11dpo buy discount flexeril 15mg online. Therefore the simple distinction between direct and indirect injuries is more useful for prognosis medicine 852 cheap flexeril 15mg free shipping. Purely ligamentous injury to the Lisfranc ligament is possible and is seen in patients with usually subtle injuries medicine 93 flexeril 15 mg online. There have been reports of primary fusion of Lisfranc joints for pure ligamentous instability medicine hat news cheapest generic flexeril uk, with good results in the medium term being described by Coatzee symptoms 9dpiui order flexeril american express, although more recent research has suggested that simple fixation may prove to give results that are as good. Due to the nature of the injury, the foot develops significant swelling, and it often 7 to 10 days before surgery can be performed. In essence, the steps for fixation are, first and foremost, to reduce the keystone second metatarsal base to its correct position. Answers these are anteroposterior and oblique views of a skeletally mature left foot showing a dislocation through the Chopart joint. The talonavicular and calcaneocuboid joints are dislocated, with plantar displacement of the distal foot. For the foot, a thorough and documented neurological and vascular examination, with an assessment of the soft tissues, is mandatory. I would plan to reduce the foot in theatre under anaesthetic on the first available trauma list. I would only do this overnight if I was concerned about the viability of the foot or if there was obvious vascular compromise. Concentrating on the foot I would assess the degree of soft tissue injury, swelling, and neurovascular status. Pain that increases despite opioids and pain on passive stretch of the muscle compartments is characteristic, with evolving neurological and vascular compromise being late signs. If the diagnosis was clinically confirmed I would proceed to surgical decompression. If there was doubt I would try and measure compartment pressure, with a value of greater then 30 mmHg being highly suggestive of compartment syndrome. Up to nine compartments have been described, but these may not all be functional because some have been demonstrated to communicate with other compartments at low pressure. The nine compartments are five in the forefoot (four interosseous and the adductor hallucis) and four in the hindfoot (medial, lateral, superficial central, and calcaneal compartments). Others have disagreed, stating there may be up to six compartments with only four compartments being functionally important. The technique I use is two dorsal incisions centred over M2 and M4 passing either side to decompress the interosseous and lateral compartments. A medial incision beneath and parallel to the first metatarsal will allow decompression of the medial compartment and lateral progression will release the central compartment. To complete release of the central compartment and the calcaneal compartment an incision is made from the posterior tuberosity of the calcaneus on the medial side to the inferior portion of the first metatarsal. The abductor is retracted superiorly to allow access through the intramuscular septum to the calcaneal compartment. Injuries of fifth metatarsal can be grouped into neck, shaft, and proximal fractures. Fractures of the neck of the fifth metatarsal are uncommon and often associated with injuries of multiple metatarsals. It is not clear, but is thought to be either inversion with a fixed forefoot or adduction of the forefoot with rapid application of forces to the proximal metatarsal. The options vary between a simple Tubigrip (compression) bandage, boot and plaster cast, or functional brace. It is recommended that a non-weight-bearing plaster cast should be tried for 6 weeks first, unless in athletes or patients who wish to have it fixed surgically. Some fractures of the fifth metatarsal occur in diaphysis, often as a result of repetitive stress in runners and athletes. These range from an undisplaced fracture to established fracture with sclerosis at the fracture site and in the cortex. The treatment often is surgical with intramedullary screw fixation with or without bone grafting as there is a high rate of non-union in this group. I would like to discuss this with a foot and ankle specialist in our department, although I am confident of dealing with these fractures. The general preference is to fix these fractures using a partially threaded screw, either cannulated or simple, under radiological control. The screw should be long enough to pass the fracture line with good purchase in the bone-a 4. The surgical risks are minimal, rehabilitation is enhanced, and healing is often achieved with internal fixation. There are reports of using tension band wiring and small plates with or without bone graft. The common risk is of delayed or non-union, but infection, intra-operative fracture, sural nerve injury, and complications related to metal work can also occur. Analysis of failed surgical management of fractures of the base of the fifth metatarsal distal to the tuberosity: the Jones fracture. There is a dorsally and radially severely angulated midshaft ulna fracture with an associated anterior dislocation of the radiocapitellar joint. This is a Bado type I injury where there is a fracture of the ulna with an anterior dislocation of the radial head. The goal of treatment is to achieve anatomical restoration of the length, alignment, and rotation of the ulna. I would therefore debride and extend the skin wound to allow delivery of the fracture ends followed by meticulous debridement of any unviable tissue. I would reduce the fracture anatomically and, because this is a simple fracture pattern, aim for absolute stability which I would achieve by using a lag screw and 3. I would first re-check my ulna fixation, as that is the most common reason why this might occur. I would radiograph the opposite elbow to be sure the patient did not have a congenital radial head dislocation (this can occur) before proceeding to open reduction of the radial head. It may be possible to flip it out but it may need to be divided then repaired after reduction has been achieved. I would discontinue antibiotics after a maximum of 72 hours and follow the patient up every week for at least the first 3 weeks to ensure there is no late subluxation of the radial head. I would use an above-elbow plaster for 6 weeks as this is a child and stiffness will not be a major issue. This is an anteroposterior view of the right clavicle of a skeletally immature patient showing a simple fracture in the midshaft of the clavicle with over 100% displacement and shortening. Paediatric fractures are broadly classified into physeal or extraphyseal injuries. This is an extraphyseal injury and the classification is similar to that used in adults-the Allman classification. I would manage this injury by first taking a full history and making an examination of the child. The other pertinent points I would note are the presence of any open wounds, whether skin integrity is compromised, whether this is an isolated injury (polytrauma or floating shoulder), and the presence of neurovascular injury-all of which would be indications for operative stabilization. In this scenario, I would opt for conservative management in a broad arm sling with progression to mobilization as pain allows. In children, the periosteal sleeve is thick and has great propensity to remodel, especially considering the clavicle is last bone to fully ossify (at about 25 years old). Complications from clavicle fractures are therefore very rare; hence they have traditionally been treated conservatively. I am aware, however, that displaced midshaft clavicle fractures have recently gained attention in the literature. The same is thought to be true in adolescents who do not possess the same remodelling potential as younger children: most heal with some degree of malunion. Surgery has therefore been recommended as an option for older children who have displaced fracture of more than 2 cm. Nonoperative treatment compared with plate fixation of displaced midshaft clavicular fractures. Operative versus nonoperative care of displaced midshaft clavicular fractures: a meta-analysis of randomized clinical trials. Displaced clavicle fractures in adolescents: facts, controversies, and current trends. Operative versus nonoperative treatment of midshaft clavicle fractures in adolescents. If you were to manage this fracture surgically in a 15-year-old, how would you do this This is an anteroposterior view of the left shoulder of a skeletally immature patient showing an extraphyseal fracture of the proximal humerus. I would like to look at other views of a shoulder trauma series, specifically a scapular Y-view and an axillary view, to further assess the degree of displacement and to rule out dislocations. I would manage this injury by first taking a full history and examination of the child, in particular the neurological status of the limb (axillary nerve/brachial plexus) followed by plain radiographs (full shoulder trauma series) and ensuring that they are all consistent with the injury pattern. The other pertinent points I would elicit are the presence of any open wounds, whether this is an isolated injury (or polytrauma), and the presence of a vascular injury. In this scenario, based on the age of the child and the minor degree of displacement, I would opt for conservative management with a collar and cuff sling with progression to mobilization as pain allows, usually within 3 weeks. If this was an older child, say a 15-year-old, would you manage it any differently If this injury occurred in a 15-year-old I would still aim to manage it conservatively with a sling. There is no controversy in the management of proximal humeral fractures in younger children (<10 years)-regardless of the degree of displacement, they uniformly do well with non-operative management as there is tremendous remodelling potential and a wide functional arc of motion of the shoulder. However, I am aware of recent changes in thinking that suggests that an older child may benefit from operative intervention. Previous studies advocating universal conservative management of paediatric proximal humeral fractures tended to include younger children, with very few adolescents in the cohort. A recent systematic review of over 550 cases suggests that children aged over 13 may benefit from open reduction and fixation due to poorer outcomes with conservative management (shortening, varus malunion), particularly for those fractures with more displacement. If this fails, then I would proceed to open reduction via a deltopectoral approach. Other impediments to reduction include the deltoid or the presence of comminution. Once the fracture is reduced adequately, I would stabilize it with percutaneous K-wires. A recent study comparing flexible intramedullary nails with percutaneous pinning showed both to be effective in stabilizing severely displaced fractures, with nails having fewer complications but requiring a longer surgical time and higher blood loss, and they need subsequent surgical removal. Intramedullary nailing versus percutaneous pin fixation of pediatric proximal humerus fractures: a comparison of complications and early radiographic results. How would you assess a patient who had a radiograph as above but with absent radial and ulnar pulses Answers this lateral radiograph shows a displaced supracondylar humeral fracture in a paediatric patient. The distal fragment is in extension and is rotated when compared with the long axis of the humeral shaft. There is some comminution and, looking at the soft tissue shadows, I am suspicious that the distal humeral shaft has buttonholed through the brachialis. Paediatric supracondylar distal humeral fractures are classified into extension type, which account for 95% of injuries, and flexion type. First and foremost, a history should be taken to include pertinent medical information and assess the risk of non-accidental injury or neglect. A through documented neurological examination, specifically to include the anterior interosseous, ulnar, and radial nerves, is mandated. The fracture should be splinted in a position of comfort and appropriate analgesia administered. Historically, cast treatment of supracondylar fractures led to significant rates of malunion. Later, these fractures were treated as surgical emergencies, often being fixed out of hours.

This increases the sensitivit y of the inner hair cells (the actual receptor cells) treatment 2nd degree heart block order flexeril online from canada. The peripheral receptors of the vestibular system are located in the m em branous labyrinth (see petrous bone medicine tour 15mg flexeril mastercard, pp treatment improvement protocol generic 15mg flexeril. The m aculae of the utricle and saccule respond to linear acceleration symptoms 20 weeks pregnant best buy for flexeril, while the sem icircular canal organs in the ampullary crest s respond to angular (rotational) acceleration medications safe in pregnancy discount flexeril 15mg otc. Like the hair cells of the inner ear treatment vitiligo discount flexeril 15mg with amex, the receptors of the vestibular system are secondary sensory cells. The basal portions of the secondary sensory cells are surrounded by dendritic processes of bi- polar neurons with their bodies located in the vestibular ganglion. The axons from these neurons form the vestibular nerve and term inate in the four vestibular nuclei (see C). Besides input from the vestibular apparatus, these nuclei also receive sensory input (see B). Functiona l Systems Hypothalam us Cerebral cortex Thalamus Brainstem Medial rectus B Central role of the vestibular nuclei in the maintenance of balance the a erent bers that pass to the vestibular nuclei and the e erent bers that em erge from them dem onstrate the central role of these nuclei in m aintaining balance. The vestibular nuclei receive a erent input from the vestibular system, proprioceptive system (position sense, m uscles, and joint s), and visual system. They then distribute e erent bers to nuclei that control the m otor system s im portant for balance. The e erent bers from the lateral vestibular nucleus pass to the lateral vestibulospinal tract. This tract extends to the sacral part of the spinal cord, its axons term inating on m otor neurons. Functionally it is concerned with keeping the body upright, chie y by increasing the tone of the extensor m uscles. The vestibulocerebellar bers from the other three nuclei act through the cerebellum to modulate m uscular tone. All four vestibular nuclei distribute ipsilateral and contralateral axons via the m edial longitudinal fasciculus to the three m otor nuclei of the nerves to the extraocular m uscles. Unlike other receptor cells, the receptor cells of the taste buds are specialized epithelial cells (secondary sensory cells given that they do not have an axon). When these epithelial cells are chem ically stim ulated, the base of the cells releases glutam ate, which stim ulates the peripheral processes of a erent cranial nerves. Peripheral processes from pseudounipolar ganglion cells (which correspond to pseudounipolar spinal ganglion cells) term inate on the taste buds. The central portions of these processes convey taste inform ation to the gustatory part of the nucleus of the solitary tract. Their cell bodies are located in the geniculate ganglion for the facial nerve, in the inferior (petrosal) ganglion for the glossopharyngeal nerve, and in the inferior (nodose) ganglion for the vagus nerve. However, som e of the axons of the second neurons travel to an additional interm ediate station in the brainstem, the m edial parabrachial nucleus, which in turn projects (as third neurons) to the thalam us, which further projects (as fourth neurons) to the insular cortex and postcentral gyrus. Collaterals from the rst and second neurons of the gustatory a erent pathway are distributed to the superior and inferior salivatory nuclei. A erent impulses in these bers induce the secretion of saliva during eating ("salivary re ex"). Besides this purely gustatory pathway, spicy foods m ay also stim ulate trigem inal bers (not shown), which contribute to the sensation of taste. The taste buds (see C) are em bedded in the epithelium of the lingual m ucosa and are located on the surface expansions of the lingual m ucosa- vallate papillae (printhe cipal site, b), the fungiform papillae (c), and the foliate papillae (d). Ad- ditionally, isolated taste buds are located in the m ucous m em branes of the soft palate and pharynx. The surrounding serous glands of the tongue (Ebner glands), which are m ost closely associated with the vallate papillae, constantly wash the taste buds clean to allow for new tasting. Hum ans can perceive ve basic tastes: sweet, sour, salt y, bit ter, and a fth "savory" taste, called um am i, which is activated by glutam ate (a taste enhancer). Taste bud Gustatory pore Squam ous epthelium of the tongue C Microscopic structure of a taste bud (after: Chandrashekar, Hoon et al. Processes of neurons of the three above m entioned cranial nerves, which grow into the oral m ucosa from the basal side, induce the epithelium to di erentiate into the depicted taste cells (m odi ed epithelial cells). Specialized taste receptor proteins in the cell m em brane of the m icorvilli are responsible for taste perception (for details, see physiology textbooks). After low-m olecular-weight avored substances bind to the receptor proteins, a signal transduction is induced, which causes the release of glutam ate. This in turn excites the peripheral processes of the pseudounipolar neurons with the bodies in the ganglia of the m entioned three cranial nerves. Based on their features, each receptor cell is specialized in one of the ve tastes (see color coding); the entire range of the perception of taste qualities is coded within each individual taste bud. This explains why the old notion that particular areas of the tongue are sensitive to speci c taste qualities is incorrect. Their peripheral receptor-bearing processes are found in the epithelium of the nasal m ucosa, while their central processes pass to the olfactory bulb (see B for details). The olfactory bulb, where the second neurons of the olfactory pathway (m itral and tufted cells) are located, is considered an extension of the telencephalon. In front of the anterior perforated substance, the olfactory tract widens to form the olfactory trigone and split s into the lateral and m edial olfactory striae. The prepiriform area (Brodm ann area 28) is considered to be the prim ary olfactory cortex in the strict sense. Note: the prepiriform area is shaded in b, lying at the junction of the basal side of the frontal lobe and the m edial side of the temporal lobe. This nucleus is located in the olfactory trigone, which lies bet ween the t wo olfactory striae and in front of the anterior perforated substance. Am bient gyrus b Sem ilunar gyrus Diagonal stria Anterior perforated substance Note: None of these three tracts are routed through the thalam us. Thus, the olfactory system is the only sensory system that is not relayed in the thalam us before reaching the cortex. There is, however, an indirect route from the prim ary olfactory cortex to the neocortex passing throug the thalam us and term inating in the basal forebrain. The olfactory signals are further analyzed in these basal portions of the forebrain (not shown). The olfactory system is linked to other brain areas well beyond the prim ary olfactory cortex, with the result that olfactory stim uli can evoke complex em otional and behavioral responses. Noxious sm ells m ay induce nausea, while appetizing sm ells evoke watering of the m outh. Presum ably these sensations are processed by the hypothalam us, thalam us, and lim bic system (see next unit) via connections established m ainly by the m edial forebrain bundle and the m edullary striae of the thalam us. This tract also continues to the brainstem, where it stim ulates salivation in response to sm ell. At the m olecular level, the olfactory receptor proteins are located in the cilia of the sensory cells (b). Each sensory cell has only one specialized receptor protein that m ediates signal transduction when an odorant m olecule binds to it. Although hum ans are m icrosm atic, having a sense of sm ell that is feeble compared with other m am m als, the olfactory receptor proteins still m ake up 2% of the hum an genom. The prim ary olfactory sensory cells have a life span of approxim ately 60 days and regenerate from the basal cells (lifelong division of neurons). The bundled central processes (axons) from hundreds of olfactory cells form olfactory bers (a) that pass through the cribriform plate of the ethm oid bone and term inate in the olfactory bulb (see C), which lies above the cribriform plate. Mate selection in m any anim al species is known to be m ediated by olfactory im pulses that are perceived in the vom eronasal organ. Mucus-water film b To/from opposite side Olfactory tract Anterior olfactory nucleus Granule cell Apical dendrite Olfactory glom erulus Olfactory bulb Mitral cell Periglom erular cells C Synaptic patterns in an olfactory bulb Specialized neurons in the olfactory bulb, called m itral cells, form apical dendrites that receive synaptic contact from the axons of thousands of prim ary sensory cells. Axons from sensory cells with the sam e receptor protein form glom eruli with only one or a sm all num ber of m itral cells. The axon collaterals of the m itral cells pass to granule cells: both granule cells and periglomerular cells inhibit the activit y of the m itral cells, causing less sensory inform ation to reach higher centers. These inhibitory processes are believed to heighten olfactory contrast, which aids in the m ore accurate perception of sm ells. The tufted cells, which also project to the prim ary olfactory cortex, are not shown. The term "lim bic system " (Latin limbus: "border" or "fringe") was rst used by Broca in 1878, who col-lectively described the gyri surrounding the corpus callosum, diencephalon, and basal ganglia as the grand lobe limbique. The lim bic system encompasses neo-, archi- and paleocortical regions as well as subcortical nuclei. The anatom ical extent of the lim bic system is such that it can exchange and integrate inform ation bet ween the telencephalon (cerebral hem ispheres), diencephalon, and m esencephalon. Viewed from the m edial aspect of the cerebral hem ispheres, the lim bic system is seen to consist of an inner arc and an outer arc. The following nuclei are also considered part of the lim bic system but are not shown: the anterior thalam ic nucleus, habenular nucleus, dorsal tegm ental nucleus, and interpeduncular nucleus. The lim bic system is concerned with the regulation of drive and a ective behavior and plays a crucial role in m em ory and learning. Corpus callosum Cingulate gyrus Thalam ocingular tract Cingulohippocampal fibers Anterior thalam ic nuclei Mam illothalam ic tract Mam illary body Hippocam pus Fornix B Neuronal circuit (Papez circuit) View of the m edial surface of the right hem isphere. Several nuclei of the lim bic system are interconnected by a neuronal circuit (see below) called the Papez circuit after the anatom ist who rst described it. This neuronal circuit interconnect s ontogenically distinct part s of the lim bic system. It establishes a connection bet ween inform ation stored in the unconscious and conscious behavior. Note: the hippocam pal form ation has a threelayered allocortex instead of a six-layered isocortex (lower left in diagram). The m ost important a erent pathway to the hippocampus is the perforant path (blue), which extends from the entorhinal region (triangular pyram idal cells of Brodm ann area 28) to the hippocam pus (where it ends in a synapse). The neurons that project from area 28 into the hippocampus receive a erent input from m any brain regions. Includes the following telencephalic structures: cingulate gyrus, parahippocampal gyrus, hippocampal form ation, septal nuclei, and amygdala. Its diencephalic components include the anterior thalamic nucleus, mamm illary bodies, nucleus accum bens, and habenular nucleus. The m edial forebrain bundle and the dorsal longitudinal fasciculus contribute to the ber tracts of the limbic system. Periarchicortex A broad transitional zone around the hippocampus, consisting of the cingulate gyrus, the isthm us of the cingulate gyrus, and the parahippocampal gyrus 483 Neuroanatomy 20. The prim ary sensory and m otor areas are shown in red, and the areas of the association cortex are shown in di erent shades of green. More than 80% of the cortical surface area is association cortex, which is secondarily connected to the prim ary sensory or prim ary m otor areas. The neuronal processing of di erentiated behavior and intellectual perform ance takes place in the association cortex, which has increased greatly in size over the course of hum an evolution. The functional organization pat tern shown here, such as the localization of the prim ary m otor cortex in the precentral gyrus, can be dem on-strated in living subject s with m odern im aging techniques. Interestingly, the correlations described in these studies correspond reasonably well with the cortical areas de ned by Brodm ann. These brain m aps illustrate the local pat terns of cerebral blood ow at rest (a) and during m ovem ent of the right hand (b). When the right hand is m oved, increased blood ow is recorded in the left precental gyrus, which contains the m otor representation of the right hand (see m otor hom unculus in B on p. Sim ultaneous activation is noted in the sensory cortex of the postcentral region, showing that the sensory cortex is also active during m otor function (feedback loop). This provides a noninvasive m ethod for investigating the m etabolic activit y of the brain. Because no hum an brain is identical to any other, a comparison of several brains will show slight variations in the distribution of speci c functions. By superimposing the result s of exam inations in di erent brains, we can produce a ge- neralized m ap that shows the approxim ate distribution of brain functions. Both groups of subject s were given phonological tasks based on recognizing di erences in the m eaning of spoken sounds. While the fem ale subject s activated both sides of their brain when solving the tasks, the m ale subject s activated only the left side (the sectional im ages are viewed from below). Synapses in the cerebral cortex D Modulating subcortical centers the cerebral cortex, the seat of our conscious thoughts and actions, is in uenced by various subcortical centers. The part s of the lim bic system that are crucial for learning and m em ory are indicated in light red. Because lesions of the corpus callosum were once considered to have no clinical e ect s, surgical division of the corpus callosum was com m only perform ed at one tim e in epileptic patient s to keep epileptic seizures from spreading across the brain.

Water is the solvent in which most of the chemical reactions in the body take place treatment xdr tb generic flexeril 15mg on-line. Substances dissolved in a liquid are solutes medicine hunter generic flexeril 15mg visa, and the liquid in which they are dissolved is the solvent medicine descriptions cheap flexeril 15 mg online. Substances that have polar or ionized groups dissolve in water by being electrically attracted to the polar water molecules medications multiple sclerosis cheap 15 mg flexeril with visa. In water treatment plans for substance abuse 15mg flexeril with mastercard, amphipathic molecules form clusters with the polar regions at the surface and the nonpolar regions in the interior of the cluster medicine quetiapine discount flexeril line. The molecular weight of a molecule is the sum of the atomic weights of all its atoms. One mole of any substance is its molecular weight in grams and contains 6 3 1023 molecules. The acidity of a solution is determined by its free hydrogen ion concentration; the greater the hydrogen ion concentration, the greater the acidity. Hydrogen bonds between peptide bonds along a polypeptide force much of the chain into an alpha helix or beta pleated sheet (secondary structure). Covalent disulfide bonds can form between the sulfhydryl groups of cysteine side chains to hold regions of a polypeptide chain close to each other; together with hydrogen bonds, ionic bonds, hydrophobic interactions, and van der Waals forces, this creates the final conformation of the protein (tertiary structure). Nucleic acids are responsible for the storage, expression, and transmission of genetic information. Both types of nucleic acids are polymers of nucleotides, each containing a phosphate group; a sugar; and a base of carbon, hydrogen, oxygen, and nitrogen atoms. The chains are held together by hydrogen bonds between purine and pyrimidine bases in the two chains. The most abundant monosaccharide in the body is glucose (C6H12O6), which is stored in cells in the form of the polysaccharide glycogen. Most lipids have many fewer polar and ionized groups than carbohydrates, a characteristic that makes them nearly or completely insoluble in water. Triglycerides (fats) form when fatty acids are bound to each of the three hydroxyl groups in glycerol. Phospholipids contain two fatty acids bound to two of the hydroxyl groups in glycerol, with the third hydroxyl bound to phosphate, which in turn is linked to a small charged or polar compound. The polar and ionized groups at one end of phospholipids make these molecules amphipathic. Steroids are composed of four interconnected rings, often containing a few hydroxyl and other groups. One fatty acid (arachidonic acid) can be converted to a class of signaling substances called eicosanoids. Proteins, macromolecules composed primarily of carbon, hydrogen, oxygen, and nitrogen, are polymers of 20 different amino acids. Amino acids are bound together by peptide bonds between the carboxyl group of one amino acid and the amino group of the next. The primary structure of a polypeptide chain is determined by (1) the number of amino acids in sequence and (2) the type of amino acid at each position. Describe the electrical charge, mass, and location of the three major subatomic particles in an atom. Describe the distinguishing characteristics of the three classes of essential chemical elements found in the body. How many covalent bonds can be formed by atoms of carbon, nitrogen, oxygen, and hydrogen What is the molar concentration of 80 g of glucose dissolved in sufficient water to make 2 L of solution What effect does increasing the pH of a solution have upon the ionization of a carboxyl group Describe the types of interactions that determine the conformation of a polypeptide chain. At that point, he went to a local emergency room, where he was subjected to a number of tests that revealed a disorder in his red blood cells due to an abnormal form of the protein hemoglobin. The three-dimensional (tertiary) structure of each subunit spatially aligns the individual amino acids in such a way that the bonding forces exert themselves between specific amino acid side groups. Therefore, anything that disrupts the tertiary structure of hemoglobin also disrupts the way in which subunits bond with one another. Such individuals are carriers of the gene that causes -Continued next page Chemical Composition of the Body and Its Relation to Physiology 41 An athletic, 21-year-old African-American male in good health spent part of the summer before his senior year in college traveling with friends in the western United States. Although not an experienced mountain climber, he joined his friends in a professionally guided climb partway up Mt. Despite his overall fitness, the rigors of the climb were far greater than he expected, and he found himself breathing heavily. At an elevation of around 6000 feet, he began to feel twinges of pain on the left side of his upper abdomen. By the time he reached 9000 feet, the pain worsened to the point that he stopped climbing and descended the mountain. Reflect and Review #1 Which level or levels of protein structure may be altered by a mutation in a gene Glutamic acid has a charged, polar side group, whereas valine has a nonpolar side group. Thus, in hemoglobin containing the mutation, one type of intermolecular bonding force is replaced with a completely different one, and this can lead to abnormal bonding of hemoglobin subunits with each other. This happens most noticeably when the amount of oxygen in the red blood cell is decreased. Such a situation can occur at high altitude, where the atmospheric pressure is low and consequently the amount of oxygen that diffuses into the lung circulation is also low. However, in the event of a sudden, large increase in the number of sickled cells, the spleen can become overfilled with damaged cells and painfully enlarged. Why would our subject attempt to climb a mountain to high altitude, knowing that the available amount of oxygen in the air is decreased at such altitudes Individuals with sickle-cell trait produce enough normal hemoglobin to be symptom free their entire lives and may never know that they are carriers of a mutated gene. However, when pushed to the limits of oxygen deprivation by high altitude and exercise, as our subject was, the result is sickling of some of the red blood cells. Clinical term: sickle-cell trait See Chapter 19 for complete, integrative case studies. Match the following compounds with choices (a) monosaccharide, (b) disaccharide, or (c) polysaccharide: Sucrose Glucose Glycogen Fructose Starch 7. Potassium has an atomic number of 19 and an atomic mass of 39 (ignore the possibility of isotopes for this question). How many neutrons and electrons are present in potassium in its nonionized (K) and ionized (K1) forms A protein is a functional molecule formed by the folding of a polypeptide into a characteristic shape, or conformation. At other times, hepatic glycogen can be broken down into many glucose molecules, which are released back into the blood and from there are transported to all cells. The breakdown of glucose within cells supplies the energy required for most cellular activities. A fascinating view inside real human bodies that also incorporates animations to help you understand the chemistry underlying physiological mechanisms. The human body is composed of trillions of cells with highly specialized structures and functions, but you learned in Chapter 1 that most cells can be included in one of four major functional and morphological categories: muscle, connective, nervous, and epithelial cells. In this chapter, we briefly describe the structures that are common to most of the cells of the body regardless of the category to which they belong. Having learned the basic structures that make up cells, we next turn our attention to how cellular proteins are synthesized, secreted, and degraded, and how proteins participate in the chemical reactions required for cells to survive. As described in Chapter 2, proteins have a unique shape or conformation that is established by their primary, secondary, tertiary, and-in some cases-quaternary structures. This conformation enables them to bind specific molecules on portions of their surfaces known as binding sites. This chapter includes a discussion of the properties of protein-binding sites that apply to all proteins, as well as a description of how these properties are involved in one special class of protein functions-the ability of enzymes to accelerate specific chemical reactions. We then apply this information to a description of the multitude of biochemical reactions involved in metabolism and cellular energy balance. As you read this chapter, think about where the following general principles of physiology apply. The general principle that structure is a determinant of-and has coevolved with-function was described at the molecular level in Chapter 2; in Section A of this chapter, you will see how that principle is important at the cellular level, and in Sections C and D at the protein level. Also in Sections C and D, you will see how the general principle that physiological processes are dictated by the laws of chemistry and physics applies to protein function. The general principle that homeostasis is essential for health and survival will be explored in Sections D and E. Finally, the general principle that physiological processes require the transfer and balance of matter and energy will be explored in Section E. To form an image with an electron beam, most of the electrons must pass through the specimen, just as light passes through a specimen in a light microscope. However, electrons can penetrate only a short distance through matter; therefore, the observed specimen must be very thin. Cells to be observed with an electron microscope must be cut into sections on the order of 0. Cellular Structure, Proteins, and Metabolic Pathways 45 Nucleus Nuclear envelope some particles and filaments, are known as cell organelles. The cytoplasm contains cell organelles and fluid surrounding the organelles, known as the cytosol. As described in Chapter 1, the term intracellular fluid refers to all the fluid inside a cell-in other words, cytosol plus the fluid inside all the organelles, including the nucleus. The chemical compositions of the fluids in cell organelles may differ from that of the cytosol. Although membranes perform a variety of functions that are important in physiology (Table 3. The plasma membrane regulates the passage of substances into and out of the cell, whereas the membranes surrounding cell organelles allow the selective movement of substances between the organelles and the cytosol. One of the advantages of restricting the movements of molecules across membranes is confining the products of chemical reactions to specific cell organelles. The hindrance a membrane offers to the passage of substances can be altered to allow increased or decreased flow of molecules or ions across the membrane in response to various signals. In addition to acting as a selective barrier, the plasma membrane has an important function in detecting chemical signals from other cells and in anchoring cells to adjacent cells and to the extracellular matrix of connective-tissue proteins. Structures that appear as separate objects in the electron micrograph may actually be continuous structures connected through a region lying outside the plane of the section. As an analogy, a thin section through a ball of string would appear to be a collection of separate lines and disconnected dots even though the piece of string was originally continuous. Two classes of cells, eukaryotic cells and prokaryotic cells, can be distinguished by their structure. The cells of the human body, as well as those of other multicellular animals and plants, are eukaryotic (true-nucleus) cells. These cells contain a nuclear membrane surrounding the cell nucleus and also contain numerous other membrane-bound structures. What is immediately obvious from both figures is the extensive structure inside the cell. Cells are surrounded by a limiting barrier, the plasma membrane (also called the cell membrane), which covers the cell surface. The cell interior is divided into a number of compartments surrounded by membranes. These membrane-bound compartments, along with 46 Chapter 3 Membrane Structure the structure of membranes determines their function, just one of a great many cellular illustrations of the general principle of physiology that structure is a determinant of-and has coevolved with- function. One end of a phospholipid has a charged or polar region, and the remainder of the molecule, which consists of two long fatty acid chains, is nonpolar; therefore, phospholipids are amphipathic (see Chapter 2). The phospholipids in plasma membranes are organized into a bilayer with the nonpolar fatty acid chains in the middle. The polar regions of the phospholipids are oriented toward the surfaces of the membrane as a result of their attraction to the polar water molecules in the extracellular fluid and cytosol. The lipid bilayer accounts for one of the fundamental functions of plasma membranes, that of acting as a barrier to the movement of polar molecules into and out of cells. With some exceptions, chemical bonds do not link the phospholipids to each other or to the membrane proteins. This results in considerable random lateral movement of both membrane lipids and proteins parallel to the surfaces of the bilayer. Like a piece of cloth, a membrane can be bent and folded but cannot be significantly stretched without being torn. As you will learn in Chapter 4, these structural features of membranes permit cells to undergo important physiological processes such as exocytosis and endocytosis, and to withstand slight changes in volume due to osmotic imbalances. The plasma membrane also contains cholesterol, whereas intracellular membranes contain very little. Like the phospholipids, therefore, cholesterol is inserted into the lipid bilayer with its polar region at the bilayer surface and its nonpolar rings in the interior in association with the fatty acid chains. The polar hydroxyl group forms hydrogen bonds with the What compartments constitute the entire intracellular fluid Regulate the passage of substances into and out of cells and between cell organelles and cytosol.

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