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Symptoms are diverse some part of the body); weakness of an and unpredictable discount ketoconazole cream 15 gm without prescription, appearing in varying extremity; visual disturbances purchase ketoconazole cream 15 gm without prescription, such as combinations and patterns purchase 15 gm ketoconazole cream amex. Consequent- diplopia (double vision) and dimness of ly discount ketoconazole cream 15 gm, not all persons with a diagnosis of mul- vision; and vertigo (dizziness or false sen- tiple sclerosis experience the same symp- sation of circular movement) buy ketoconazole cream 15 gm low price. There may be partial er extremities; unsteadiness; visual or complete paralysis of any part of the problems; or poor bowel and bladder con- body or spasticity of muscles, especially in trol. Symptoms of the hands, called intention tremor, may fluctuate, becoming worse at times (exac- be present. The tremor is called intention erbation) and better at other times (re- tremor because it occurs only when the mission) (Antel & Bar-Or, 2003). Because of the vari- may also have difficulty in swallowing ability and fluctuation of symptoms, diag- (dysphagia), which can contribute to nosis of the condition is often a chal- choking. Before being diagnosed with mul- Multiple sclerosis may also affect the tiple sclerosis, many individuals have genitourinary tract, causing incontinence gone from one health provider to anoth- (loss of control of the bladder or bowel). Men may experience erectile dys- dition is not recognized or diagnosed function and women may experience immediately because the symptoms have decrease in sexual desire, lubrication prob- 106 CHAPTER 3 CONDITIONS OF THE NERVOUS SYSTEM: PART II lems, or inorgasmia (McCabe, McDonald, A variety of medications may be used to Deeks, Vowels, & Cobain, 1996). Some medica- ever, women with multiple sclerosis are tions may exacerbate symptoms or ad- able to become pregnant and carry preg- versely affect remaining function, and nancy to term. There is no evidence that some have the potential to impair mem- pregnancy causes an increase in symp- ory and learning. Consequently, the type toms or exacerbations of the condition of medication prescribed varies with the (Hansell, 1995). Medications are commonly Some individuals experience cognitive used for bladder management, control of changes as a result of multiple sclerosis, spasticity, or emotional symptoms. Some individuals, however, ple sclerosis never experience urinary may experience impairment in perform- problems, for those who do, anticholiner- ing tasks that require conceptualization, gic medications, which inhibit the actions memory, or new learning, as well as diffi- of the parasympathetic nervous system, culty with tasks that require either rapid are sometimes helpful in relieving bladder or precise motor responses. Depression is com- stimulate the actions of the parasympa- mon, although the degree to which it is a thetic nervous system, may be helpful in reaction to the disease or a manifestation relieving urinary retention. Bladder training may be helpful in reducing bladder problems Treatment and Management of and in helping the individual to manage Multiple Sclerosis bladder control. Use of a catheter or san- itary pads may also decrease the embar- The diagnosis of multiple sclerosis is rassment of possible leakage of urine. There is no specific ids are ingested and ensuring a ready treatment for multiple sclerosis, nor is availability of restrooms to minimize the there a cure. If individuals have ed toward controlling individual symp- problems with urinary retention, they toms and preventing exacerbations and may be taught to insert a catheter into complications. Relaxants or antispasmod- toms, but it can have risks that must be ics may be prescribed for muscle spasm or carefully weighed by each individual. There is no steroids taken over extended periods of formula for estimating the general out- time, they are usually prescribed only on come for all individuals. Symptoms often a temporary basis to decrease exacerba- fluctuate with periods of remission (when tions, and not as ongoing therapy. Al- or anxiety may have antianxiety agents or though the symptoms may partly resolve antidepressants prescribed. Since suicide when the disease is in remission, exacerba- rates are relatively high among individu- tions can leave permanent residual defects. The general prognosis for individuals In general, individuals with multiple with multiple sclerosis is unpredictable, sclerosis should remain as active as they with varying rates of progression and can without developing excessive fatigue. For some indi- Physical therapy may be prescribed to help viduals (about 20 percent) the condition with problems of mobility or with the use remains relatively stable with only mild of assistive devices, such as walkers, if symptoms, such as slight weakness, needed. Specific exercises that help to de- unsteadiness, or vision problems, and no crease calcium loss from bones, strength- long-term disability. The majority of indi- en weak muscles, and maintain muscle viduals (about 65 percent) develop a strength and joint mobility may also be relapsing-remitting pattern in which there prescribed. Physical therapy that includes are continuing exacerbations when symp- massage and passive range-of-motion toms become worse with periods of com- exercises may also be beneficial. Indi- plete or partial remission in which there viduals with multiple sclerosis who expe- is no significant overall disability or rience speech problems may be referred to restriction of general activity. Many of a speech therapist or may use assistive these individuals retain their mobility 20 devices, such as a communication board or more years after diagnosis, with limit- and voice amplifier. For some in- sclerosis, exposure to heat can have a tem- dividuals the disease progresses slowly porary adverse effect on symptoms. En- with no remissions and gradually increas- vironments in which body temperature is ing disability. Still others experience rap- increased, such as during hot or humid id progression with total disability.

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Blood Flow Is Higher in the Renal Cortex In the tubuloglomerular feedback mechanism cheap ketoconazole cream 15 gm fast delivery, the transient increase in GFR resulting from an increase in and Lower in the Renal Medulla blood pressure leads to increased solute delivery to the Blood flow rates differ in different parts of the kidney (Fig cheap 15gm ketoconazole cream fast delivery. Blood flow is highest in the cortex cheap 15gm ketoconazole cream amex, averaging 4 to tubular fluid [NaCl] at this site and increased NaCl reab- 5 mL/min per gram of tissue discount ketoconazole cream 15gm with amex. By mechanisms that are permits a high rate of filtration in the glomeruli 15 gm ketoconazole cream fast delivery. Blood still uncertain, constriction of the nearby afferent arteriole flow (per gram of tissue) is about 0. The relatively low blood flow in the medulla feedback sensitivity varies directly with the local concen- helps maintain a hyperosmolar environment in this region tration of angiotensin II. The tubuloglomerular feedback 386 PART VI RENAL PHYSIOLOGY AND BODY FLUIDS mechanism is a negative-feedback system that stabilizes renal blood flow and GFR. Autoregulatory If NaCl delivery to the macula densa is increased exper- range imentally by perfusing the lumen of the loop of Henle, fil- 1. This sug- gests that the purpose of tubuloglomerular feedback may be to control the amount of Na presented to distal nephron segments. Regulation of Na delivery to distal Renal blood flow parts of the nephron is important because these segments have a limited capacity to reabsorb Na. Without renal autoregulation, increases in arterial blood pressure would lead to dramatic increases in GFR and potentially serious losses of NaCl and water from the ECF. Sympathetic nerve stimulation causes renal vasocon- 0 40 80 120 160 200 240 striction and a consequent decrease in renal blood flow. Mean arterial blood pressure (mm Hg) Renal sympathetic nerves are activated under stressful condi- Renal autoregulation, based on measure- tions, including cold temperatures, deep anesthesia, fearful FIGURE 23. In the autoregulatory range, renal blood flow and GFR conditions, the decrease in renal blood flow may be viewed stay relatively constant despite changes in arterial blood pressure. The circles indicate that vessel radius (r) and heart, which are more important for short-term survival. Since resistance to blood flow varies as r , including adenosine, angiotensin II, endothelin, epineph- changes in vessel caliber are greatly exaggerated in this figure. Other substances cause vasodilation in the kidneys, includ- ing atrial natriuretic peptide, dopamine, histamine, kinins, nitric oxide, and prostaglandins E2 and I2. An increase in sympathetic nerve activ- ity or plasma angiotensin II concentration stimulates the production of renal vasodilator prostaglandins. These prostaglandins then oppose the pure constrictor effect of sympathetic nerve stimulation or angiotensin II, reducing the fall in renal blood flow, preventing renal damage. GLOMERULAR FILTRATION Glomerular filtration involves the ultrafiltration of plasma. This term reflects the fact that the glomerular filtration bar- rier is an extremely fine molecular sieve that allows the fil- tration of small molecules but restricts the passage of macromolecules (e. The Glomerular Filtration Barrier The tubuloglomerular feedback mecha- Has Three Layers FIGURE 23. When single nephron GFR is in- An ultrafiltrate of plasma passes from glomerular capillary creased—for example, as a result of an increase in arterial blood pressure—more NaCl is delivered to and reabsorbed by the mac- blood into the space of Bowman’s capsule through the ula densa, leading to constriction of the nearby afferent arteriole. This barrier con- This negative-feedback system plays a role in renal blood flow sists of three layers. Chicago: Year Book, 1974; and Brenner BM, Bohrer MP, Baylis C, ers of the glomerular filtration barrier: en- dothelium, basement membrane, and podocytes. The second layer, the basement membrane, consists are large molecules, so they are not appreciably filtered. From studies with molecules of different sizes, it has been The third layer is composed of podocytes, which consti- calculated that the glomerular filtration barrier behaves as tute the visceral layer of Bowman’s capsule. However, no one has ever seen pores nate in foot processes, which rest on the outer layer of the of this size in electron micrographs of the glomerular filtra- basement membrane (see Fig. For a given molecular weight, a slender and flexible component of the diaphragm is a molecule called molecule will pass through the glomerular filtration barrier nephron, which forms a zipper-like structure; between the more easily than a spherical, nondeformable molecule. The nephron is Electrical charge influences the passage of macromole- mutated in congenital nephrotic syndrome, a rare, inher- cules through the glomerular filtration barrier because the ited condition characterized by excessive filtration of barrier bears fixed negative charges. The glomerular filtrate normally takes an lial cells and podocytes have a negatively charged surface extracellular route, through holes in the endothelial cell coat (glycocalyx), and the glomerular basement membrane layer, the basement membrane, and the pores between ad- contains negatively charged sialic acid, sialoproteins, and jacent nephron molecules. These negative charges impede the pas- sage of negatively charged macromolecules by electrostatic repulsion and favor the passage of positively charged Size, Shape, and Electrical Charge Affect macromolecules by electrostatic attraction. This is sup- the Filterability of Macromolecules ported by the finding that the filterability of dextran is low- The permeability properties of the glomerular filtration est for anionic dextran, intermediate for neutral dextran, barrier have been studied by determining how well mole- and highest for cationic dextran (see Table 23. Molecular radii were charge on serum albumin at physiological pH is an impor- calculated from diffusion coefficients.

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