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Without external adaptive devices order 20mcg atrovent otc medications kidney patients should avoid, cipient is crucial to prevent serious aller- such as wheelchairs atrovent 20 mcg discount medicine 72, crutches, or canes, or gic reactions, which could be fatal. In any other signs of disability, individuals addition to the risk of such a reaction, may react by denying the seriousness of there is a risk that a blood transfusion will their condition and resist medical direc- transmit a disease, such as hepatitis or tives. For example, individuals with hemo- HIV, although careful screening by philia may engage in risk-taking behaviors, blood banks has significantly reduced even though injury and subsequent bleed- this risk. Individuals with sickle Psychosocial Issues in Conditions Affecting the Blood or Immune System 253 cell anemia may engage in a flurry of ac- variety of ways, ranging from the adop- tivity, even though the associated stress tion of a philosophical view toward life to and fatigue may precipitate a sickle cell passivity and withdrawal. Individuals with HIV infection may The way in which individuals cope with withhold their diagnosis from others with a condition they have had since child- whom they engage in sexual activity, even hood depends on a wide variety of factors, though their behavior could put those some of which relate to the coping mech- others at risk. Individuals’ Some disorders occur later in life, neces- reaction as an adult to their condition is sitating adjustment at the time the disabil- dependent to some extent on how well ity occurs. Disorders such as sickle cell their psychological adjustment was man- anemia and hemophilia are lifelong disor- aged throughout development. Consequently, individuals who were encouraged to live as normal a with these disorders have had to cope life as possible, despite their condition, with their condition in one way or anoth- may exhibit a greater sense of self-esteem er from childhood into adulthood, and and autonomy as adults than do those most of them have experienced frequent who were kept in a dependent, overpro- illness and medical care throughout their tected state. Although these experiences can build confidence in Lifestyle Issues the ability to cope with adversity, they can also have a negative impact on develop- Different conditions affecting the blood ment. Individuals may carry the coping or immune system affect activities of dai- behaviors and attitudes learned in child- ly living in varying degrees, depending on hood into the adult years, where they con- the associated symptoms. Symptoms of tinue to affect their perception of them- fatigue or difficulty in breathing with exer- selves, their condition, and their abilities. Although hemophilia can everyone; however, because of the in- be controlled to some degree, there is creased susceptibility to infection that is always the fear that an accident or trau- part of many conditions affecting the matic event may occur in which bleeding blood or immune system (especially HIV may not be controlled. Individuals with infection), individuals must take extra care sickle cell anemia are aware of the possi- to have well-balanced diets and well-bal- bility that sudden death will occur as a anced regimens of rest and activity. Exer- result of a sickle cell crisis or complica- cise is especially important to individuals tions. Regular, moderate exer- know that their progression to AIDS will cise can build the muscles that protect probably result in death. Individuals may joints and decrease the incidence of cope with the threat of early death in a bleeding into the joints. However, activi- 254 CHAPTER 8 CONDITIONS OF THE BLOOD AND IMMUNE SYSTEM ties that carry a higher probability of in- continuing medical care. Because these jury, such as contact sports, should be individuals do not appear to be legitimate- avoided. For the Conditions that are hereditary and those most part, individuals with hemophilia that occur in childhood can impair the need not interrupt their daily schedules. Recurrent hospitalizations may greatly reduced their incapacity by provid- affect children’s school performance and, ing prompt and early treatment of spon- consequently, their sense of industry and taneous bleeding. In addition, frequent school Although neither hemophilia nor sick- absences, hospitalizations, or the inabili- le cell anemia alters sexual function, both ty to engage in some activities may affect are inherited disorders, and individuals children’s interactions and relationships may wish to consider genetic counseling with peers, which, in turn, could affect before deciding to have children. The parents of a child with an inher- partners about their diagnosis prior to sex- ited disorder, such as hemophilia or sick- ual contact and should engage only in safe le cell anemia, may experience guilt, react sexual practices. When women with HIV with overprotectiveness, or foster a sense infection become pregnant, the child of dependency in the child. They may also excuse the child from the normal responsibilities The social effects of conditions affecting or the limits established for the child’s sib- the blood or immune system vary with lings. Such parental reactions can impede the condition, the individual, and the par- the child’s ability to function adequately ticular circumstances. SYSTEM Because many conditions affecting the blood or immune system have no readily The cause and symptoms of a condition observable outward cues and signs, and be- affecting the blood or immune system cause symptoms are often intermittent, determine its vocational impact. If, for others may not understand why individ- example, the condition has been caused uals with these conditions must adhere to in part by exposure to toxic substances certain restrictions or why they are under within the environment, the hazards Case Studies 255 should be removed before individuals re- reasons and because his health insurance turn to the workplace. He also tells nea is a symptom of the condition, as in you that work has been therapeutic for those conditions characterized by anemia, him after the loss of his partner. When infec- his job performance; however, lately he tion is a potential complication of the dis- states he has had more difficulty keeping order, individuals should avoid exposure up with the physical demands at work to factors and environments that may pre- because of fatigue and in the past few cipitate infection. The functional impact weeks he has developed lymphadenopa- of immune disorders is also dependent on thy. With HIV medication that he also believes might infection, for example, prior to the devel- have some side effects that could interfere opment of severe immunodeficiency, no with his ability to work.

Although ACh does not have a primary excitatory role like glutamate in the CNS purchase atrovent 20mcg with mastercard treatment yeast infection men, it does increase neuronal excitability and responsiveness buy 20 mcg atrovent amex medications such as seasonale are designed to, through activation of muscarinic receptors. It achieves this in two ways, both of which involve closure of K‡ channels (see Chapter 2 and Brown 1983; Brown et al. The first is a voltage- dependent K‡ conductance called the M conductance, Gm or Im. It is activated by any ACETYLCHOLINE 127 attempt to depolarise the neuron, when the openingof the M-channel and the consequent efflux of K‡ counteracts the depolarisation and limits the generation of spikes. This current is inhibited by activation of muscarinic receptors and so ACh will tend to keep the neuron partially depolarised and facilitate repetitive firingand bust spiking. This slow cholinergic excitation in hippocampal neurons is shown in Fig. The slow epsp was selectively potentiated by the anticholinesterase drugeserine (2 mM) with the generation of action potentials. This firing and the slow epsp, but not the fast epsp or ipsp, were eliminated by the muscarinic antagonist atropine (0. The iontophoretic application of ACh (right-hand traces) in the presence of eserine only produced the slow epsp and superimposed firingwhich were also antagonised by atropine (resting membrane potentials 57±60 mV). These recordings show that the slow but not the fast epsp is cholinergic. Micropipette application of glutamate (10 ms of 1 mM) caused a rapid generation of action potentials up to 100 mV in amplitude while ACh (40 ms of 1 mM) only generated smaller (10±20 mV) potentials more slowly (50 ms) with larger ones (30±50 mV) appearinglater. These results again demonstrate the slow excitatory effect produced by ACh compared with the larger and more rapid primary depolarisation of glutamate. This is not voltage activated but is switched on by Ca2‡ entry through channels opened during the initial depolar- isation. It is inhibited by activation of muscarinic receptors and so its reduction will also lead to repetitive firing. ACh in fact seems to dampen the inbuilt brakes on cell firing (see also Chapter 2 and Figs 2. M1 and M3 receptors mediate the excitatory effects and since this postspike hyper- polarisation is blocked by phorbol esters and is therefore presumably dependent on IP3 production, one would expect it to be mediated through M1 receptors (see above), especially as these are located postsynaptically. Unfortunately it does not appear to be affected by pirenzapine, the M1 antagonist. By contrast, muscarinic inhibition of the M current is reduced by the M1 antagonist but as it is not affected by phorbol esters is not likely to be linked to IP3 production, an M1 effect. ACh can sometimes inhibit neurons by increasingK‡ conductance and although it has been found to hyperpolarise thalamic neurons, which would normally reduce firing, strongdepolarisation may still make the cell fire even more rapidly than normal. This appears to be because the hyperpolarisation counters the inactivation of a low- threshold Ca2‡ current which is then activated by the depolarisation to give a burst of action potentials (McCormick and Prince 1986b). AGONISTS AND ANTAGONISTS Many drugs bind to cholinergic receptors but few of them enter the brain and those that do are not noted for their effects. AGONISTS Some agonists, such as methacholine, carbachol and bethanecol are structurally very similar to ACh (Fig. They are all more resistant to attack by cholinesterase than ACh and so longer acting, especially the non-acetylated carbamyl derivatives carbachol and bethanecol. Carbachol retains both nicotinic and muscarinic effects but the presence of a methyl (CH3) group on the b carbon of choline, as in methacholine and bethanecol, restricts activity to muscarinic receptors. Beingcharged lipophobic com- pounds they do not enter the CNS but produce powerful peripheral parasympathetic effects which are occasionally used clinically, i. Pilocarpine, arecoline and, of course, muscarine itself are naturally occurring muscarinic agonists, while oxotremorine is a synthetic one, which, as its name implies, can cause muscle tremor through a central effect. Few drugs, apart from nicotine itself, act specifically on nicotine receptors. One is methylcarbachol, which lacks the muscarinic effects of carbachol and another is dimethylphenylpiperazinium (DMPP), which appears to have some selectivity for the neuronal nicotinic receptor. Acetylcholine has the structure to activate both muscarinic and nicotinic receptors. Carbachol retains these actions but is longer acting because it lacks the terminal methyl group and is not so readily hydrolysed by cholinesterase (see Fig.

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Histology © The McGraw−Hill Anatomy order atrovent 20 mcg visa treatment math definition, Sixth Edition of the Body Companies order atrovent 20mcg medicine overdose, 2001 Chapter 4 Histology 81 (b) (c) (a) FIGURE 4. Simple squamous epithelia that line the lumina of vessels are referred to as endothelia, and that which cover visceral or- gans are referred to as mesothelia. Many membranous epithelia are exposed to friction or spherical central nucleus. This epithelium is adapted for diffusion harmful substances from the outside environment. It occurs in the pulmonary alveoli within the son, epithelial tissues have remarkable regenerative abilities. The lungs (where gaseous exchange occurs), in portions of the kidney mitotic replacement of the outer layer of skin and the lining of (where blood is filtered), on the inside walls of blood vessels, in the GI tract, for example, is a continuous process. Membranous epithelia are histologically classified by the The simple squamous epithelium lining the inner walls of blood number of layers of cells and the shape of the cells along the ex- and lymphatic vessels is termed endothelium (en″do-the′le-um) posed surface. That which covers visceral organs and lines body cav- layer of cells are called simple; those that are layered are said to ities is called mesothelium (mes″o˘-the′le-um). Squamous cells are flattened; cuboidal cells are cube- shaped; and columnar cells are taller than they are wide. Simple Cuboidal Epithelium Simple cuboidal epithelium is composed of a single layer of Simple Epithelia tightly fitted cube-shaped cells (fig. This type of epithelium is found lining small ducts and tubules that have excretory, se- Simple epithelial tissue is a single cell layer thick and is located cretory, or absorptive functions. It occurs on the surface of the where diffusion, absorption, filtration, and secretion are principal ovaries, forms a portion of the tubules within the kidney, and functions. The cells of simple epithelial tissue range from thin, lines the ducts of the salivary glands and pancreas. Some of these cells have cilia that create currents for the movement of materials across cell surfaces. Others have microvilli that increase the surface Simple Columnar Epithelium area for absorption. The height of the cells varies, depending on the Simple Squamous Epithelium site and function of the tissue. Each cell contains a single nu- cleus which is usually located near the basement membrane. Simple squamous (skwa′mus) epithelium is composed of flat- tened, irregularly shaped cells that are tightly bound together in a mosaiclike pattern (fig. Histology © The McGraw−Hill Anatomy, Sixth Edition of the Body Companies, 2001 82 Unit 3 Microscopic Structure of the Body Lumen of renal tubule Basement membrane Nucleus (c) FIGURE 4. Liver Stomach Gallbladder Large intestine Small intestine (b) (b) Lumen of small intestine Nucleus Creek Basement (a) membrane Goblet cell Cilia (c) FIGURE 4. Histology © The McGraw−Hill Anatomy, Sixth Edition of the Body Companies, 2001 Chapter 4 Histology 83 Body of uterus Uterine tube Uterine cavity Paras (b) Ovary Lumen of uterine tube Cilia (a) Vagina Cell membrane Nucleus Basement membrane (c) FIGURE 4. Specialized unicellular glands called goblet cells are scattered The tissue appears to be stratified because the nuclei of the cells through this tissue at most locations. Numerous goblet cells and a cili- bricative and protective mucus along the free surfaces of the ated exposed surface are characteristic of this epithelium. Simple columnar epithelium is found lining the inside walls found lining the inside walls of the trachea and the bronchial of the stomach and intestine. In the digestive system, it forms a tubes; hence, it is frequently called respiratory epithelium. Its func- highly absorptive surface and also secretes certain digestive tion is to remove foreign dust and bacteria entrapped in mucus chemicals. Within the stomach, simple columnar epithelium has from the lower respiratory system. Coughing and sneezing, or simply “clearing the throat,” are protective reflex mechanisms for clearing the respiratory pas- Simple Ciliated Columnar Epithelium sages of obstruction or of inhaled particles that have been trapped in the mucus along the ciliated lining. The material that is coughed up Simple ciliated columnar epithelium is characterized by the pres- consists of the mucus-entrapped particles. Cilia produce wavelike movements that transport materials through tubes or passage- Stratified Epithelia ways.

The amount of oxyhemoglo- would become only slightly more saturated (97 to 98%) buy atrovent 20mcg low price symptoms 5 days before missed period. In the pulmonary capillaries buy atrovent 20mcg lowest price symptoms in early pregnancy, where PO2 is high, the bly by hyperventilation. The steep unloading phase of the reaction is shifted to the right to form oxyhemoglobin. In curve allows large quantities of oxygen to be released or un- tissue capillaries, where PO2 is low, the reaction is shifted to loaded from hemoglobin in the tissue capillaries where a the left; oxygen is unloaded from hemoglobin and becomes lower capillary PO prevails. The maximum amount of oxygen that equilibrium curve enables oxygen to saturate hemoglobin can be carried by hemoglobin is called the oxygen carrying under high partial pressures in the lungs and to give up capacity—about 20 mL O2/dL blood in a healthy young large amounts of oxygen with small changes in PO at the 2 adult. The P —the PO at which 50% 50 2 bound to hemoglobin (whereas capacity is the amount that of the hemoglobin is saturated—provides a functional way can potentially be bound). The percentage saturation of to assess the binding affinity of hemoglobin for oxygen. A 50 bin content over capacity: high P signifies a decrease in hemoglobin’s affinity for 50 Hb O2 content oxygen and results in a rightward shift in the oxyhemoglo- SO2 100 (5) bin equilibrium curve, whereas a low P50 signifies the op- Hb O2 capacity posite and shifts the curve to the left. A shift in the P50 in Thus, the oxygen saturation is the ratio of the quantity either direction has the greatest effect on the steep phase of oxygen actually bound to the quantity that can be poten- and only a small effect on the loading of oxygen in the nor- tially bound. For example, if oxygen content is 16 mL O2/dL mal lung, because loading occurs at the plateau. The curve is S-shaped and O2 in physical solution can be divided into a plateau region and a steep region. CHAPTER 21 Gas Transfer and Transport 355 A carbon dioxide (high PCO2), all of which favor the unload- 100 ing of more oxygen to metabolically active muscles. Red blood cells contain 2,3-diphosphoglycerate (2,3- Shift to left DPG), an organic phosphate compound that also can affect 80 (P50 ↓) Shift to right affinity of hemoglobin for oxygen. In red cells, 2,3-DPG (P50 ↑) levels are much higher than in other cells because erythro- cytes lack mitochondria. An increase in 2,3-DPG facilitates 60 unloading of oxygen from the red cell at the tissue level Normal P50 (shifts the curve to the right). An increase in red cell 2,3- DPG occurs with exercise and with hypoxia (e. Oxygen content, rather than PO2or SaO2, is what keeps us 20 alive and serves as a better gauge for oxygenation. For exam- ple, an individual can have a normal arterial PO2 and SaO2 but reduced oxygen content. This situation is seen in patients 0 20 40 60 80 100 120 140 who have anemia (a decreased number of circulating red cells). A patient with anemia who has a hemoglobin concen- PO2 (mm Hg) B tration half of normal (7. A patient with anemia has a normal SaO2because that content and capacity are proportionally re- 80 duced. The usual oxyhemoglobin equilibrium curve does not show changes in blood oxygen content, since the vertical axis is saturation. If the vertical axis is changed to oxygen content 60 (mL O /dL blood), then changes in content are seen (Fig. The shape of the oxyhemoglobin equilibrium curve PCO2↑, pH↓ does not change, but the curve moves down to reflect the re- 40 duction in oxygen content. A good analogy for comparing an anemic patient with a normal patient is a bicycle tire and a 20 truck tire: both can have the same air pressure, but the amount of air each tire holds is different. Carbon monoxide interferes PO (mm Hg) with oxygen transport by competing for the same binding 2 sites on hemoglobin. Carbon monoxide binds to hemoglo- Hemoglobin (Hb) binding affinity for O2. B, An increase in temperature, [H ], or arte- 50 rial PCO2 causes a rightward shift of the oxyhemoglobin equilib- rium curve. A P increase indicates that binding affinity for oxy- 20 50 gen decreases, which favors the unloading of O2 from Hb at the tissue level. An increase in red cell levels of 2,3-diphosphoglycer- Normal blood ate (DPG) will also shift the curve to the right. Several factors affect the binding affinity of hemoglobin for Anemia O2, including temperature, arterial carbon dioxide tension, 5 (40% of normal) and arterial pH.

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