At the same time that Na is actively pumped from the basal side of the cell – + into the interstitial fluid order silagra 100mg without prescription, Cl follows the Na from the lumen into the interstitial fluid by a paracellular route between cells through leaky tight junctions silagra 100mg amex. These are found between cells of the ascending loop buy genuine silagra on-line, where they allow certain solutes to + move according to their concentration gradient order on line silagra. Most of the K that enters the cell via symporters returns to the lumen (down its concentration gradient) through leaky channels in the apical membrane. Note the environment now created in the + + – interstitial space: With the “back door exiting” K , there is one Na and two Cl ions left in the interstitium surrounding the ascending loop. Therefore, in comparison to the lumen of the loop, the interstitial space is now a negatively charged + + ++ ++ environment. This negative charge attracts cations (Na , K , Ca , and Mg ) from the lumen via a paracellular route to the interstitial space and vasa recta. Countercurrent Multiplier System The structure of the loop of Henle and associated vasa recta create a countercurrent multiplier system (Figure 25. The countercurrent term comes from the fact that the descending and ascending loops are next to each other and their fluid flows in opposite directions (countercurrent). The multiplier term is due to the action of solute pumps that increase (multiply) the + concentrations of urea and Na deep in the medulla. This results in the recovery of NaCl to the circulation via the vasa recta and creates a high osmolar environment in the depths of the medulla. Urea is not only less toxic but is utilized to aid in the recovery of water by the loop of Henle and collecting ducts. At the same time that water is freely diffusing out of the descending loop through aquaporin channels into the interstitial spaces of the medulla, urea freely diffuses into the lumen of the descending loop as it descends deeper into the medulla, much of it to be reabsorbed from the forming urine when it + reaches the collecting duct. Thus, the movement of Na and urea into the interstitial spaces by these mechanisms creates the hyperosmotic environment of the medulla. The net result of this countercurrent multiplier system is to recover both water + and Na in the circulation. The presence of aquaporin channels in the descending loop allows prodigious quantities of water to leave the loop and enter the hyperosmolar interstitium of the pyramid, where it is returned to the circulation by the vasa recta. As the loop turns to become the ascending loop, there is an absence of aquaporin channels, so water cannot leave the loop. This mechanism works to dilute the fluid of the ascending loop ultimately to approximately 50–100 mOsmol/L. They are recovering both solutes and water at a rate that preserves the countercurrent multiplier system. The flow must be slow to allow blood cells to lose and regain water without either crenating or bursting. Second, a rapid + flow would remove too much Na and urea, destroying the osmolar gradient that is necessary for the recovery of solutes + and water. Thus, by flowing slowly to preserve the countercurrent mechanism, as the vasa recta descend, Na and urea are + freely able to enter the capillary, while water freely leaves; as they ascend, Na and urea are secreted into the surrounding medulla, while water reenters and is removed. The movement of Na out of the lumen – of the collecting duct creates a negative charge that promotes the movement of Cl out of the lumen into the interstitial space by a paracellular route across tight junctions. In addition, as Na is pumped out of the cell, the resulting electrochemical gradient attracts ++ Ca into the cell. Finally, calcitriol (1,25 dihydroxyvitamin D, the active form of vitamin D) is very important for calcium ++ recovery. These binding proteins are also important for the movement of calcium inside the cell and aid in exocytosis of calcium across the basolateral ++ membrane. Collecting Ducts and Recovery of Water Solutes move across the membranes of the collecting ducts, which contain two distinct cell types, principal cells and intercalated cells. As in other portions of the nephron, there is an array of micromachines (pumps and channels) on display in the membranes of these cells. By varying the amount of water that is recovered, the collecting ducts play a major role in maintaining the body’s normal osmolarity. If the blood becomes hyperosmotic, the collecting ducts recover more water to dilute the blood; if the blood becomes hyposmotic, the collecting ducts recover less of the water, leading to concentration of the blood. Another way of saying this is: If plasma osmolarity rises, more water is recovered and urine volume decreases; if plasma osmolarity decreases, less water is recovered and urine volume increases. As the ducts descend through the medulla, the osmolarity surrounding them increases (due to the countercurrent mechanisms described above). If aquaporin water channels are present, water will be osmotically pulled from the collecting duct into the surrounding interstitial space and into the peritubular capillaries. By also stimulating aldosterone production, it provides a longer-lasting mechanism to support blood pressure by maintaining vascular volume (water recovery). As + + + the pump recovers Na for the body, it is also pumping K into the forming urine, since the pump moves K in the opposite + + direction. When aldosterone decreases, more Na remains in the forming urine and more K is recovered in the circulation. Still other channels in the principal cells secrete K into the collecting duct + in direct proportion to the recovery of Na. This rate determines how much solute is retained or discarded, how much water is retained or discarded, and ultimately, the osmolarity of blood and the blood pressure of the body. Sympathetic Nerves The kidneys are innervated by the sympathetic neurons of the autonomic nervous system via the celiac plexus and splanchnic nerves. Reduction of sympathetic stimulation results in vasodilation and increased blood flow through the kidneys during resting conditions. When the frequency of action potentials increases, the arteriolar smooth muscle constricts (vasoconstriction), resulting in diminished glomerular flow, so less filtration occurs. Under conditions of stress, sympathetic nervous activity increases, resulting in the direct vasoconstriction of afferent arterioles (norepinephrine effect) as well as stimulation of the adrenal medulla. The adrenal medulla, in turn, produces a generalized vasoconstriction through the release of epinephrine. This includes vasoconstriction of the afferent arterioles, further reducing the volume of blood flowing through the kidneys. Autoregulation The kidneys are very effective at regulating the rate of blood flow over a wide range of blood pressures. This is due to two internal autoregulatory mechanisms that operate without outside influence: the myogenic mechanism and the tubuloglomerular feedback mechanism. Arteriole Myogenic Mechanism The myogenic mechanism regulating blood flow within the kidney depends upon a characteristic shared by most smooth muscle cells of the body. When you stretch a smooth muscle cell, it contracts; when you stop, it relaxes, restoring its resting length. When blood pressure increases, smooth muscle cells in the wall of the arteriole are stretched and respond by contracting to resist the pressure, resulting in little change in flow. When blood pressure drops, the same smooth muscle cells relax to lower resistance, allowing a continued even flow of blood. This mechanism stimulates either contraction or relaxation of afferent arteriolar smooth muscle cells (Table 25. Specialized macula densa cells in this segment of the tubule respond to changes in the fluid flow rate and Na concentration. It is produced in the lungs but binds to the surfaces of endothelial cells in the afferent arterioles and glomerulus. It acts systemically to cause vasoconstriction as well as constriction of both the afferent and efferent arterioles of the glomerulus. Its release is usually stimulated by decreases in blood pressure, and so the preservation of adequate blood pressure is its primary role. At the + + same time that aldosterone causes increased recovery of Na , it also causes greater loss of K. It binds to the aldosterone receptor and weakly stimulates Na reabsorption and increased water recovery. It may cause increased retention of water during some periods of the menstrual cycle in women when progesterone levels increase. It promotes the recovery of water, decreases urine volume, and maintains plasma osmolarity and blood pressure.

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While this is an efficient system silagra 50mg fast delivery, the truth is that five different patients with a diagnosis of depression generic 100 mg silagra with amex, for example order silagra master card, can have symptoms due to five completely different etiologies best silagra 100 mg. Thus, five different treatment plans may be in order, not a generic approach based strictly on diagnosis. Two such etiologies that can deceive a psychiatrist’s diagnostic eye are allergies and toxins. While treating symptoms 60 | Complementary and Alternative Medicine Treatments in Psychiatry pharmaceutically may help to some degree, a far more effective approach for improving wellness would be to identify and treat the allergy or toxicosis. Allergies and Mental Health An allergy is a hypersensitivity disorder of the immune system. Substances which should be innocuous create a reaction in the individual ranging from bothersome to life-threatening. Allergens activate the antibody Immunoglobulin E (IgE), which, in turn, triggers mast cells and basophils, resulting in an extreme inflammatory response. Allergies can affect any or multiple systems of the body, including digestive, respiratory, cardiovascular, endocrine, and neurological. The same substance—latex, for example—that can cause one person to break out in hives can cause a different individual to have a panic attack. Symptoms may not be as recognizable as those of allergic rhinitis, with sniffling and sneezing. Psychiatric symptoms, in particular, even when they are of strictly physiological origin, may be mistakenly assigned to life situations, stress, or other blameworthy causes. Although the most common allergy-related psychiatric symptoms that have been studied are depression and anxiety, given the variability of human response to allergies, any psychiatric symptom, including psychosis, has the potential of being allergy-induced. Therefore, allergies must be considered as a potential causative agent, whether a patient has intermittent symptoms or chronic. For example, a person sensitive to mold who lives in an area that had recent flooding may respond with chronic depression for months if mold spores or mycotoxins are continuously The Role of Allergies, Poisons, and Toxins in Psychiatry | 61 present. Mold can also exist for years in locations such as heating, ventilation, and air conditioning systems, causing continuous exposure at home or work. Depression and Anxiety It is well established that inflammation and inflammatory mechanisms play a critical role in major depression. Elevations in proinflammatory cytokines and other inflammation-related proteins are common in depressive disorders (Raedler 2011). It should not be too surprising then to find that 71% of people with depression also have a history of allergies (Bell 1991). It is also known that depression scores increase with the exacerbation of allergy symptoms and that cytokines are elevated in the prefrontal cortex in victims of suicide (Postolache 2007). There is an overwhelming preponderance of studies showing the relationship between allergies and depression (and anxiety). The causal relationship includes the triggering of the immune system and cytokines, the impairment of sleep through nasal obstruction resulting in psychiatric symptoms, and the negative effect on cognitive function associated with allergies (Sansone 2011). Gastrointestinal inflammation also may be a significant contributing factor to depression (Fehér 2011). Given that allergies commonly impact the respiratory and cardiovascular systems, it comes as no surprise that restricted breathing or asthma with accompanying tachycardia, so frequently found with allergies, is a common trigger for anxiety 62 | Complementary and Alternative Medicine Treatments in Psychiatry and panic attacks. As with depression, as allergy scores increase, so do anxiety symptoms (Postolache 2008). Additionally, it’s been found that allergic rhinitis worsens existing psychiatric symptoms. The behavior of somatization, compulsion, depression and anxiety in patients with a history of eczema or asthma is much more obvious than in patients without such a history. Nasal obstruction has a conspicuous impact on somatization, compulsion, interpersonal sensitivity, depression, anxiety and psychosis, while nasal itching contributes to somatization, depression and anxiety (Lv 2010). An inflammatory reaction atrophies the villi lining of the small intestine, resulting in reduced ability to absorb nutrients, minerals and the fat-soluble vitamins A, D, E, and K. Until recently, the standard approach to finding celiac disease has been to wait for people to complain of symptoms and to come to the doctor for investigation. We may need to consider looking for celiac disease in the general population, more like we do in testing for cholesterol or blood pressure. Standard testing includes blood levels of the antibodies anti-endomysium and anti-tissue transglutaminase. If 64 | Complementary and Alternative Medicine Treatments in Psychiatry these are positive, an endoscopic biopsy of the small intestine is done to confirm the diagnosis (U Chicago Tests). Poisons and Toxins A poison is a substance that can cause disturbance to an organism through chemical reaction or other activity on a molecular scale. Thus, mercury is a poison and mycotoxins— metabolites produced by molds—are toxins. It is incumbent upon the practitioner to consider this factor when a patient presents with psychiatric symptoms. A particularly revealing question is, “Does anyone in your (neighborhood, factory, home, etc. Most medical students are told how the phrase “mad as a hatter” comes from the fact that mercury used by hat makers of old commonly resulted in a deteriorating psychosis. However, the list of substances that cause psychiatric symptoms is actually quite long—with new ones being The Role of Allergies, Poisons, and Toxins in Psychiatry | 65 discovered continuously—and far too extensive for us to cover in this brief publication, though we can give some examples. Hydrogen sulfide—common to volcanic eruptions, tanneries, and some paper mills—can affects mood states and the psychological stress response. In animal studies, it has been shown to alter levels of the neurotransmitters serotonin, norepinephrine, dopamine, aspartate and glutamate. Carbon disulfide, also a neurotoxin, has been linked to personality changes, mood disorders and suicides in occupational settings. A Duke University study, looking into why two neighborhoods in North Carolina had 10 times the state’s suicide rate and 6. Hydrogen sulfide levels reached as much a ten times the acceptable standard (Duke Medicine 2004). When farm workers receive what they consider to be a toxic level of exposure to pesticides with organophosphates, it has been found they have nearly six times the rate of depression as the general public (Stallones 2002). Particulate air pollution, a pervasive exposure in modern urban environments, has been found to alter brain structure and cause cognitive impairment and depressive symptoms. Mice exposed to pollutants at the same levels of modern city inhabitants were found to have not only depressed states, but elevated cytokine expression in the hippocampus and altered dendrite growth (Fonken 2011). The treatment for toxic exposure will vary depending on the substance but the first line of defense would be, if possible, removal of the offending material. In the case of occupational or 66 | Complementary and Alternative Medicine Treatments in Psychiatry habitat exposures, difficult choices may be involved requiring finding new employment or changing living quarters. Summary With allergies increasing and toxic exposures on the rise in our increasingly industrialized world, psychiatric symptoms from these environmental causes are also becoming more prominent. A wise physician, on the lookout for such risk factors, could save a patient years or even a lifetime of misdiagnosis and add years of more healthful living to what might otherwise be an existence of slow and mysterious decline. Breathing Technique, Mindfulness, and Yoga Christine Berger Abdominal Breathing Abdominal breathing, also called diaphragmatic breathing or belly breathing, is a core activity of meditation and yoga practices and an important therapeutic technique in its own right. Various Eastern religious and philosophical traditions cite the breath as a bridge connecting mind-body-emotions-spirit (Brown 2009). Anxious or depressed individuals breathe only from the upper chest, in a shallow fashion, whereas individuals who have an integrated mind-body system breathe deeply, from the diaphragm. Therefore, for clients with anxiety disorders or depression, it follows that breath training can serve as an empowering adjunctive treatment for these mental health challenges (Weil 2006). In fact, according to Philippott et al, cited by Brown and Gerbarg, changing breath patterns therapeutically “can account for at least 40% in feelings of anger, fear, joy and sadness” (Brown 2009). When practiced, it appropriately energizes the sympathetic nervous system on the inhale, and the exhale appropriately engages the parasympathetic system (Brown 2009). Proper breathing manages energy, breath volume, and adjusts other biological systems such as the endocrine, digestive, circulatory and neurochemical. Regulation of breath regulates heart function through the vagus nerve (Edwards 2008). The Impact of Breathing on Anxiety and Depression While Americans often think of yoga as a series of meditative postures, the system of yoga includes an emphasis on various breathing techniques which induce a variety of desired states.

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The roles of T and B lymphocytes in the adaptive immune response will be discussed further in this chapter discount generic silagra uk. A plasma cell is a B cell that has differentiated in response to antigen binding buy silagra 50mg visa, and has thereby gained the ability to secrete soluble antibodies 100 mg silagra overnight delivery. These cells differ in morphology from standard B and T cells in that they contain a large amount of cytoplasm packed with the protein-synthesizing machinery known as rough endoplasmic reticulum generic silagra 100mg without a prescription. Natural Killer Cells A fourth important lymphocyte is the natural killer cell, a participant in the innate immune response. Primary Lymphoid Organs and Lymphocyte Development Understanding the differentiation and development of B and T cells is critical to the understanding of the adaptive immune response. It is through this process that the body (ideally) learns to destroy only pathogens and leaves the body’s own cells relatively intact. The lymphoid organs are where lymphocytes mature, proliferate, and are selected, which enables them to attack pathogens without harming the cells of the body. Later, the bone marrow takes over most hematopoietic functions, although the final stages of the differentiation of some cells may take place in other organs. The red bone marrow is a loose collection of cells where hematopoiesis occurs, and the yellow bone marrow is a site of energy storage, which consists largely of fat cells (Figure 21. The B cell undergoes nearly all of its development in the red bone marrow, whereas the immature T cell, called a thymocyte, leaves the bone marrow and matures largely in the thymus gland. Thymus The thymus gland is a bilobed organ found in the space between the sternum and the aorta of the heart (Figure 21. The trabeculae and lobules, including the darkly staining cortex and the lighter staining medulla of each lobule, are clearly visible in the light micrograph of the thymus of a newborn. The connective tissue capsule further divides the thymus into lobules via extensions called trabeculae. The outer region of the organ is known as the cortex and contains large numbers of thymocytes with some epithelial cells, macrophages, and dendritic cells (two types of phagocytic cells that are derived from monocytes). The medulla, where thymocytes migrate before leaving the thymus, contains a less dense collection of thymocytes, epithelial cells, and dendritic cells. Immune System By the year 2050, 25 percent of the population of the United States will be 60 years of age or older. One major cause of age-related immune deficiencies is thymic involution, the shrinking of the thymus gland that begins at birth, at a rate of about three percent tissue loss per year, and continues until 35–45 years of age, when the rate declines to about one percent loss per year for the rest of one’s life. At that pace, the total loss of thymic epithelial tissue and thymocytes would occur at about 120 years of age. Animal studies have shown that transplanted thymic grafts between inbred strains of mice involuted according to the age of the donor and not of the recipient, implying the process is genetically programmed. Sex hormones such as estrogen and testosterone enhance involution, and the hormonal changes in pregnant women cause a temporary thymic involution that reverses itself, when the size of the thymus and its hormone levels return to normal, usually after lactation ceases. The potential is there for using thymic transplants from younger donors to keep thymic output of naïve T cells high. The more we learn through immunosenescence research, the more opportunities there will be to develop therapies, even though these therapies will likely take decades to develop. The ultimate goal is for everyone to live and be healthy longer, but there may be limits to immortality imposed by our genes and hormones. Secondary Lymphoid Organs and their Roles in Active Immune Responses Lymphocytes develop and mature in the primary lymphoid organs, but they mount immune responses from the secondary lymphoid organs. In addition to circulating in the blood and lymph, lymphocytes concentrate in secondary lymphoid organs, which include the lymph nodes, spleen, and lymphoid nodules. All of these tissues have many features in common, including the following: • The presence of lymphoid follicles, the sites of the formation of lymphocytes, with specific B cell-rich and T cell-rich areas • An internal structure of reticular fibers with associated fixed macrophages • Germinal centers, which are the sites of rapidly dividing and differentiating B lymphocytes • Specialized post-capillary vessels known as high endothelial venules; the cells lining these venules are thicker and more columnar than normal endothelial cells, which allow cells from the blood to directly enter these tissues Lymph Nodes Lymph nodes function to remove debris and pathogens from the lymph, and are thus sometimes referred to as the “filters of the lymph” (Figure 21. Any bacteria that infect the interstitial fluid are taken up by the lymphatic capillaries and transported to a regional lymph node. Dendritic cells and macrophages within this organ internalize and kill many of the pathogens that pass through, thereby removing them from the body. The lymph node is also the site of adaptive immune responses mediated by T cells, B cells, and accessory cells of the adaptive immune system. Like the thymus, the bean- shaped lymph nodes are surrounded by a tough capsule of connective tissue and are separated into compartments by trabeculae, the extensions of the capsule. In addition to the structure provided by the capsule and trabeculae, the structural support of the lymph node is provided by a series of reticular fibers laid down by fibroblasts. The micrograph of the lymph nodes shows a germinal center, which consists of rapidly dividing B cells surrounded by a layer of T cells and other accessory cells. Cells and lymph fluid that leave 986 Chapter 21 | The Lymphatic and Immune System the lymph node may do so by another set of vessels known as the efferent lymphatic vessels. Lymph enters the lymph node via the subcapsular sinus, which is occupied by dendritic cells, macrophages, and reticular fibers. Within the cortex of the lymph node are lymphoid follicles, which consist of germinal centers of rapidly dividing B cells surrounded by a layer of T cells and other accessory cells. As the lymph continues to flow through the node, it enters the medulla, which consists of medullary cords of B cells and plasma cells, and the medullary sinuses where the lymph collects before leaving the node via the efferent lymphatic vessels. It is about 12 cm (5 in) long and is attached to the lateral border of the stomach via the gastrosplenic ligament. The spleen is a fragile organ without a strong capsule, and is dark red due to its extensive vascularization. The spleen is sometimes called the “filter of the blood” because of its extensive vascularization and the presence of macrophages and dendritic cells that remove microbes and other materials from the blood, including dying red blood cells. The marginal zone is the region between the red pulp and white pulp, which sequesters particulate antigens from the circulation and presents these antigens to lymphocytes in the white pulp. Upon entering the spleen, the splenic artery splits into several arterioles (surrounded by white pulp) and eventually into sinusoids. Blood from the capillaries subsequently collects in the venous sinuses and leaves via the splenic vein. The red pulp consists of reticular fibers with fixed macrophages attached, free macrophages, and all of the other cells typical of the blood, including some lymphocytes. The white pulp surrounds a central arteriole and consists of germinal centers of dividing B cells surrounded by T cells and accessory cells, including macrophages and dendritic cells. Lymphoid Nodules The other lymphoid tissues, the lymphoid nodules, have a simpler architecture than the spleen and lymph nodes in that they consist of a dense cluster of lymphocytes without a surrounding fibrous capsule. These nodules are located in the respiratory and digestive tracts, areas routinely exposed to environmental pathogens. Tonsils are lymphoid nodules located along the inner surface of the pharynx and are important in developing immunity to oral pathogens (Figure 21. The tonsil located at the back of the throat, the pharyngeal tonsil, is sometimes referred to as the adenoid when swollen. Histologically, tonsils do not contain a complete capsule, and the epithelial layer invaginates deeply into the interior of the tonsil to form tonsillar crypts. These structures, which accumulate all sorts of materials taken into the body through eating and breathing, actually “encourage” pathogens to penetrate deep into the tonsillar tissues where they are acted upon by numerous lymphoid follicles and eliminated. This seems to be the major function of tonsils—to help children’s bodies recognize, destroy, and develop immunity to common environmental pathogens so that they will be protected in their later lives. Tonsils are often removed in those children who have recurring throat infections, especially those involving the palatine tonsils on either side of the throat, whose swelling may interfere with their breathing and/or swallowing. Peyer’s patches contain specialized endothelial cells called M (or microfold) cells that sample material from the intestinal lumen and transport it to nearby follicles so that adaptive immune responses to potential pathogens can be mounted. Any discussion of the innate immune response usually begins with the physical barriers that prevent pathogens from entering the body, destroy them after they enter, or flush them out before they can establish themselves in the hospitable environment of the body’s soft tissues. The different modes of barrier defenses are associated with the external surfaces of the body, where pathogens may try to enter (Table 21. Not only is the skin covered with a layer of dead, keratinized epithelium that is too dry for bacteria in which to grow, but as these cells are continuously sloughed off from the skin, they carry bacteria and other pathogens with them. Additionally, sweat and other skin secretions may lower pH, contain toxic lipids, and physically wash microbes away. Barrier Defenses Site Specific defense Protective aspect Skin Epidermal surface Keratinized cells of surface, Langerhans cells Sweat glands, sebaceous Skin (sweat/secretions) Low pH, washing action glands Oral cavity Salivary glands Lysozyme Stomach Gastrointestinal tract Low pH Mucosal surfaces Mucosal epithelium Nonkeratinized epithelial cells Normal flora (nonpathogenic Prevent pathogens from growing on mucosal Mucosal tissues bacteria) surfaces Table 21. Additionally, the mucus layer of the gastrointestinal tract, respiratory tract, reproductive tract, eyes, ears, and nose traps both microbes and debris, and facilitates their removal. In the case of the upper respiratory tract, ciliated epithelial cells move potentially contaminated mucus upwards to the mouth, where it is then swallowed into the digestive tract, ending up in the harsh acidic environment of the stomach.