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The extensor movement of the first toe in response to Reference stroking the plantar aspect of the foot 10mg torsemide amex, termed Babinski Drachman DA discount 10mg torsemide with mastercard. JAMA sign, is thought to occur because of modification of flexor 1998;280:2111–2118. The Cushing response (described by famous neurosurgeon flex when the plantar surface is stimulated. Harvey Cushing) consists of the development of hyperten- The neurophysiological details of how the deficit in sion, bradycardia, and apnea in patients with increased in- corticospinal input actually produces these commonly tracranial pressure most often a result of tumors or other le- encountered abnormalities in muscle tone and reflex sions, such as hemorrhage, that compress the brain. A current theory is pressure is transmitted downward to the brainstem and dis- that the disturbance of central control reduces the torts the medulla, where the centers for blood pressure, threshold of the stretch reflex but does not alter its gain. Correct interpre- References tation of these abnormalities in vital signs permits begin- Lance JW. The control of muscle tone, reflexes, and move- ning treatments that reduce intracranial pressure. Quantitative relations an artificial respirator, and then instituting hyperventilation between hypertonia and stretch reflex threshold in spastic to lower the blood PCO2 to produce cerebral vasoconstric- hemiparesis. Another autonomic reaction from the CNS that is uti- CASE STUDY FOR CHAPTER 6 lized daily in hospitals is the response of fetal heart rate Autonomic Dysfunction as a Result of CNS Disease to compression of the head during labor. During uterine A 30-year-old patient came to the hospital emergency contractions, the fetal head is temporarily compressed. Previously he the cranium are not yet fused, the pressure of the con- had experienced only mild, infrequent tension traction is transmitted to the brain. Because of the nism of cardiac slowing as cited for the Cushing re- intensity of this new headache, he is treated with in- sponse is presumed to cause the temporary bradycardia. Additional factors, such as umbilical cord com- consciousness declines to the point of responding only pression, may also produce patterns of slowing outside to painful stimuli. The central nervous system and cardiovascular the blood is thought to be a ruptured cerebral artery control in health and disease. Philadelphia: Lippincott-Raven, 1997 During the next 24 hours, the patient’s ECG begins to show abnormalities consisting of both tachycardia and changes in the configuration of the waves suggestive of CASE STUDY FOR CHAPTER 7 a heart attack. For the preceding 2 days, the patient’s wife had no- Questions ticed that he did not seem to make sense when he spoke. What is the explanation for the cardiac abnormalities in this She also indicated that he seemed a little disoriented situation? Describe two other scenarios in which there are prominent has no obvious motor or somatic sensory deficits. The consulting cardiologist reviewed the situation and man’s visual fields and notices a decreased awareness stated that the ECG abnormalities were all a result of sub- of stimuli presented to one visual field. What information from the case history gives the answers stimulate excessive activity of the sympathetic nervous to questions 1 and 2? The stroke involved the superior posterior temporal lobe en- norepinephrine from sympathetic nerve endings and epi- compassing Wernicke’s area and the occipital lobe encom- nephrine by the adrenal medulla. Language deficits indicate involvement of the left hemi- duce the same ECG abnormalities in experimental ani- sphere. The fluent but nonsensical speech indicates involve- mals as were found in this patient. The visual field deficit indicates a lease of norepinephrine and epinephrine stimulates the loss in the visual cortex. The lack of motor or somatic sen- cardiac conducting system and may also produce direct sory deficits excludes the posterior frontal and anterior pari- damage of the myocardium. The right visual field would be affected, because visual ters can be lifesaving. PART III Muscle Physiology CHAPTER Contractile Properties of Muscle Cells Richard A. Changes in the length of a skeletal muscle result in anatomic location, histological structure, and mode of con- changes in the degree of overlap of the myofilaments. Skeletal (striated) muscle is used for voluntary movement transform the energy stored in ATP into mechanical energy of the skeleton. Cardiac muscle provides the motive power for circulation bridges to release from the actin filaments. The contractile proteins of muscle are arranged into two the cumulative effects of millions of crossbridges acting to overlapping sets of myofilaments, one predominantly move myofilaments past one another. Crossbridge interaction and the events of the crossbridge containing (thin).

This release is prevented by an inhibitor of GABA uptake but unaffected by the presence of GABAA receptor antagonists generic 10 mg torsemide otc, such as bicuculline 20mg torsemide. There is no doubt that this form of release depends on vesicular exocytosis because it is Ca2‡-dependent, sensitive to tetrodotoxin and, like impulse- dependent release, it is attenuated by a2-adrenoceptor agonists (see above). The extent to which this process occurs under normal physiological conditions in vivo remains to be seen. NEURONAL REUPTAKE OF NORADRENALINE In common with other monoamines, the actions of released noradrenaline are terminated by its rapid reuptake from the synaptic cleft. This uptake process relies on membrane-bound noradrenaline transporters which are glycoproteins closely related Figure 8. Binding domains for specific ligands are thought to be within regions indicated by the solid bars. All these transporters have 12 hydrophobic transmembrane domains (TMDs), a large hydrophyllic loop between TM3 and TM4, and intracellular N- and C-termini. The hypothetical structure of the noradrenaline transporter is illustrated in Fig. Because co-transport of both Cl7 and Na‡ is required for the uptake of noradrenaline, this is regarded as one of the family of Na‡/Cl7 transporters. Exactly how this transporter carries noradrenaline across the neuronal membrane is not known but one popular model proposes that it can exist in two interchangeable states. This process enables the translocation of noradrenaline from the extracellular space towards the neuronal cytosol. Point-mutation and splicing studies indicate that different zones of the transporter determine its substrate affinity and selectivity, ionic dependence, Vmax, and the binding site for uptake inhibitors such as desipramine (Povlock and Amara 1997). Because the cloned transporter is a target for the reuptake inhibitor, desipramine, it is thought to reflect the native transporter in the brain and peripheral tissues. These are quite distinct uptake mechanisms because they have different substrate affinities and antagonist sensitivities. As yet, few studies have investigated the possibility that more than one uptake process exists in the brain but since two mRNAs for noradrenaline transporters have been isolated from brain tissue (Pacholczyk, Blakely and Amara 1991) there could be more than one transcription factor. At the very least, intracellular messengers could modify substrate affinity of the transporter, by causing its phosphorylation or glycosylation (Bonisch, Hammermann and Bruss 1998), and so markedly affect its function. Whether or not there are different gene products, splice variants, or posttranslational changes, it has been suggested that abnormal distributions of functionally distinctive noradrena- line transporters could underlie some psychiatric and neurological disorders. METABOLISM After reuptake into the cytosol, some noradrenaline may be taken up into the storage vesicles by the vesicular transporter and stored in the vesicles for subsequent release (see above). However, it is thought that the majority is broken down within the cytosol of the nerve terminal by monoamine oxidase (MAO; EC1. The metabolic pathway for noradrenaline follows a complex sequence of alternatives because the metabolic product of each of these enzymes can act as a substrate for the other (Fig 8. This could enable one of these enzymes to compensate for a deficiency in the other to some extent. MAO is bound to the outer membrane of mitochondria and is responsible for the oxidative deamination of noradrenaline. There are two isoforms of this enzyme, MAO-A 176 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Figure 8. MAO is responsible for the oxidative deamination of noradrenaline derivatives while COMT O-methylates noradrenaline. Most intraneuronal metabolism involves MAO while COMT is mainly found extraneuronally. The reasons for this complex network of metabolites are not known and MAO-B, which hybridise to different cDNAs and are encoded by different genes on the X chromosome. MAO-A is the more important in vivo because it preferentially metabolises noradrenaline. However, in vitro, MAO-B will metabolise noradrenaline at high substrate concentrations. MAO probably also has an important role in development: a genetic deficiency of MAO-A causes some mental retardation and a tendency to bouts of aggression.

Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN:Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 19 nxiety S order 10 mg torsemide overnight delivery. STANFORD INTRODUCTION Emotional states that would now be classified as anxiety were recognised as long ago as the classical Greek period but have undergone many phases of medical classification since then buy generic torsemide 20mg. The extent to which they share a common neurobiological basis is far from clear but it is evident that different anxiety disorders do not all respond to the same drug treatments. In fact, it is antidepressant drugs, especially the selective serotonin reuptake inhibitors (SSRIs), that are turning out to be the most effective treatments for some anxiety disorders and their use has undoubtedly been encouraged by fears that prolonged treatment with benzodiazepines might induce a dependence syndrome. The beneficial effects of antidepressants in anxiety are often interpreted as support for a neurobiological link between anxiety and depression. Also, because anxiety often progresses to depression and because these disorders can co-exist in the same patients, it has even been suggested that they might be different manifestations of a single problem (Tyrer 1989). However, whereas anxiety drives people to seek medical help, the response to stress is a normal physiological event. A distinctive feature of anxiety, therefore, is that it can be regarded as an inappropriate stress response that is chronic or intermittent, for which the stimulus is either not obvious (as in GAD) or irrational (as in the phobias), or provokes a prolonged emotional disturbance (as in post-traumatic stress disorder). The first is to establish experimental models of anxiety in animals and humans in order to discover its neuro- biological basis. The second is to investigate the actions of anti-anxiety drugs in the brain in the hope that this will give some clues to the cause(s) of anxiety. Webster &2001 John Wiley & Sons Ltd 396 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Table 19. Agoraphobia: Fear of places or situations from which escape is difficult Ð can occur with or without a history of panic disorder Social phobia: Fear of social or performance situations Specific phobia: Fear of a specific object or situation ANXIETY STATES Panic disorder (with or without agoraphobia): Recurrent unexpected panic attacks Generalised anxiety disorder: At least 6 months of persistent and excessive anxiety and worry Obsessive compulsive disorder: Obsessions (which cause anxiety) and or compulsions (which serve to neutralise anxiety) Post-traumatic stress disorder (PTSD): Re-experiencing of traumatic event outside normal human experience with increased arousal and avoidance of stimuli associated with the trauma Acute stress disorder: Symptoms similar to PTSD but occur within 1 month of the traumatic event Anxiety disorder due to a general medical condition: e. Disorders of thyroid function, cardiovascular system, respiratory system, head injury, etc. Caffeine, cocaine, alcohol Anxiety disorder not otherwise specified: Prominent symptoms of anxiety that do not fit any of the above categories SYMPTOMS AND SIGNS OF ANXIETY (Modified from Nutt 1990) Mood: Apprehension, worry, difficulty in concentration, irritability, insomnia Cognitions: Fear of (for example): death, ineffectiveness, failure, humiliation, mental illness Somatic: Cardiovascular (tachycardia, palpitations), sweating, respiration, GIT, muscle tension, tremor, muscle aches or soreness, nausea, exaggerated startle reflex, increased urinary frequency Behaviour: Hypervigilance, nail-biting, scratching ANIMAL MODELS OF ANXIETY All preclinical animal models of anxiety involve exposing animals (usually rats or mice) to environmental stimuli that disrupt their normal pattern of behaviour (Table 19. Obviously, it can never be confirmed that animals are actually experiencing the equi- valent of human anxiety and so the validity of all preclinical models rests largely on confirming that the change in behaviour is prevented by drugs that have established anti-anxiety effects in humans. The signal can either warn that behaviour which is reinforced by reward will also be punished (e. In the following sections, specific behavioural models used to study anxiety and the effects of anti- anxiety drugs are described. EVALUATING DRUG EFFECTS ON INNATE BEHAVIOUR (ETHOLOGICAL MODELS) Most of these models evaluate the effects of drugs on the behaviour of animals when they are exposed to a novel environment. When placed on the 398 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Figure 19. Animals are placed in the central zone (usually facing an open arm) and their movements scored for: number of entries to the open and closed arms and the percentage time spent in the open arms. File) apparatus for the first time, animals explore all zones of the maze but spend most time (approximately 75%) in, and make most entries to, the closed arms. Pretreatment with an anti-anxiety drug increases exploration of the open arms so that approximately equal times are spent on the open and closed arms of the maze. Detailed insight into some of the many assumptions and refinements of the use of the plus-maze is to be found in Rodgers and Dalvi (1997). Social interaction test In this test, it is the interaction (sniffing, grooming, etc. Social interaction is dependent on the familiarity of the animals with the test arena (social interaction is reduced in an unfamiliar arena) and the intensity of illumination (social interaction is reduced in bright light). The reduction in social ANXIETY 399 interaction under aversive conditions (unfamiliar arena and bright light) is prevented by pretreatment with anti-anxiety drugs (File and Hyde 1979). However, it is again important to establish that any drug effects are directed specifically at the behavioural response to the test environment, rather than overall locomotor activity. One of these, the fear-potentiated startle reflex, rests on the development of an exaggerated startle on presentation of the conditioned cue. This is named after the two scientists who developed it and is still often used to screen putative anti-anxiety drugs (Geller, Kulak and Seifter 1962). After reaching a stable response on the lever, the rats are then trained to realise that when a (normally) neutral stimulus is presented, such as a buzzer or a light, they will experience a mild footshock, as well as receive the reward, when they press on the lever. Anti-anxiety drugs abolish the inhibition of responding during the punished phase but do not affect unpunished responding (Fig. A drug-induced reduction in the discomfort caused by the footshock (as is achieved with analgesics) or amnesia (i.

This volume increases ap- proximately 100 to 150 ml/day for each 1° C elevation in body temperature order 10mg torsemide fast delivery. For each hour of hard physical work out-of-doors in the summertime torsemide 10 mg otc, a person may produce 1 to 10 L of perspiration. A serious danger of continued exposure to heat and excessive water and salt loss is heat exhaustion, characterized by nau- sea, weakness, dizziness, headache, and a decreased blood pres- sure. Heat stroke is similar to heat exhaustion, except that in heat stroke sweating is prevented (for reasons that are not clear) and body temperature rises. Red and yellow indi- Excessive heat loss triggers a shivering response in muscles, cate the warmest parts of the body. The initial symptoms of hypothermia are When the body’s heat-producing mechanisms cannot keep numbness, paleness, delirium, and uncontrolled shivering. A lengthy exposure temperature falls below 32° C (90° F), the heart loses its ability to to temperatures below 20° C (68° F) and dampness may lead to this pump blood and will go into fibrillation (erratic contractions). This is why it is so important that a hiker, for example, victim is not warmed, extreme drowsiness, coma, and death follow. Integumentary System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 114 Unit 4 Support and Movement (a) (b) FIGURE 5. During the rainy season, which may last 5 to 6 months, the children are kept indoors. Rickets develops from an improper diet and also from lack of the sunlight needed to synthesize vitamin D. Called cuta- neous receptors, these sensory nerve cells are especially abun- Because of the effective protective barriers of the integument al- dant in the skin of the face and palms, the fingers, the soles of ready described, cutaneous absorption (absorption through the the feet, and the genitalia. Some gases, such as oxygen and carbon dioxide, back and on the back of the neck and are sparse in the skin over may pass through the skin and enter the blood. Generally speaking, the thinner the UV light, necessary for synthesis of vitamin D, are absorbed read- skin, the greater the sensitivity. Of clinical consideration is the fact that certain chemicals such as lipid-soluble toxins and pesticides can easily enter the body through the skin. Communication Humans are highly social animals, and the integument plays Synthesis an important role in communication. Various emotions, such The integumentary system synthesizes melanin and keratin, which as anger or embarrassment, may be reflected in changes of remain in the skin synthesis of vitamin D, which is used elsewhere skin color. The contraction of specific facial muscles pro- in the body and begins in the skin with activation of a precursor duces facial expressions that convey an array of emotions, in- molecule by UV light. The molecule is modified in the liver and cluding love, surprise, happiness, sadness, and despair. Only small amounts of UV light are necessary for vita- frequently elicit subconscious responses from others who de- min D synthesis, but these amounts are very important to a grow- tect them. Active vitamin D enters the blood and helps regulate the metabolism of calcium and phosphorus, which are important Knowledge Check in the development of strong and healthy bones. List five modifications of the integument that are struc- turally or functionally protective. Explain how the integument functions to regulate body flu- Sensory Reception ids and temperature. Integumentary System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 5 Integumentary System 115 EPIDERMAL DERIVATIVES Hair, nails, and integumentary glands form from the epidermal layer, and are therefore of ectodermal derivation. Hair and nails are structural features of the integument and have a limited func- tional role. By contrast, integumentary glands are extremely im- portant in body defense and maintenance of homeostasis. Objective 6 Describe the structure of hair and list the three principal types. Objective 8 Compare and contrast the structure and function of the three principal kinds of integumentary glands. Humans are relatively hairless, with only the scalp, face, pubis, and axillae being densely haired. Men and women have about the same density of hair on their bodies, but hair is generally more obvious on men (fig.