The fact that the intestine seems to extract oxygen from blood before altering vascular resistance has a certain appeal for whole-body homeostatic mechanisms buy discount zudena online erectile dysfunction doctors in brooklyn. Even though effects of changes in vascular resistance in the intestine on the body as a whole are lessened by the parallel arrangement of organ circulations in the body cheap 100 mg zudena fast delivery erectile dysfunction remedy, the intestine and splanchnic circulations are still enormous purchase zudena 100 mg overnight delivery erectile dysfunction ka ilaj. Manipulating extraction of oxygen before adjusting vascular resistance and flow might be a means of meeting the metabolic needs of the intestine while minimizing the effects of those needs on the blood supply to other organs. Effects of elevated venous pressure on fluid filtration by intestinal capillaries. The intestine has one of the highest capillary filtration coefficients among organ systems in the body. This could be potentially troublesome because the small intestine has a very large anatomical capillary surface area and it is not a good autoregulator of blood flow for most of the time during the day (i. These two factors make the intestine a prime source of fluid loss in the body whenever mean capillary hydrostatic pressure increases, such as what might occur whenever arterial or venous pressure increase. Recall that, when arterial pressure is increased, strong autoregulation in an organ not only controls organ blood flow, but it also attenuates any increase in mean capillary hydrostatic pressure that would otherwise cause increased capillary fluid filtration. In a weak autoregulatory state, arteriolar constrictor responses to an increase in arterial pressure are weak and loss of fluid through the intestinal capillaries is likely. Furthermore, loss of fluid from the capillaries of the huge intestinal circulation could be significant in situations in which intestinal venous pressures rise. Such venous pressure rises can occur in liver disease or with portal vein obstructions because the intestinal veins are connected in series to the portal circulation of the liver. However, elevation of venous pressure in the intestinal circulation, which would increase capillary hydrostatic pressure, causes sustained myogenic arteriolar constriction that decreases capillary hydrostatic pressure. This is called the venous–arteriolar response and is a means by which major fluid loss from the capillaries is prevented in the intestine in the face of an elevation of intestinal venous pressure. Although the venous arteriolar response occurs in other organ systems, it appears to be strongest in the intestinal circulation. High blood flow is required in the intestinal mucosal for absorption of nutrients. The intestinal mucosa receives about 60% to 70% of the total intestinal blood flow. Blood flows of 70 to 100 mL/min/100 g in this specialized tissue are probable and much higher than the average blood flow for the total intestinal wall (see Table 16. The intestinal mucosa is composed of individual projections of tissue called villi. The interstitial space of the villi is mildly hyperosmotic (~400 mOsm/kg H O) at rest as a result of NaCl. The primary cause of high osmolalities in the2 villi appears to be greater absorption than removal of NaCl and nutrient molecules. There is also a possible countercurrent exchange process in which materials absorbed into the capillary blood diffuse from the venules into the incoming blood in the arterioles thus trapping them in the interstitium of the villus. Lipid absorption causes a greater increase in intestinal blood flow and oxygen consumption, a condition known as absorptive hyperemia, than either carbohydrate or amino acid absorption. The hyperosmotic lymph and venous blood that leave the villus to enter the submucosal tissues around the major resistance vessels are also major contributors to absorptive hyperemia. The active absorption of amino acids and carbohydrates and the metabolic processing of lipids into chylomicrons by mucosal epithelial cells place a major burden on the microvasculature of the small intestine. There is an extensive network of capillaries just below the villus epithelial cells. The villus capillaries are unusual in that portions of the cytoplasm are missing, so that the two opposing surfaces of the endothelial cell membranes appear to be fused. These areas of fusion, or closed fenestrae, are thought to facilitate the uptake of absorbed materials by capillaries. However, large molecules, such as plasma proteins, do not easily cross the fenestrated areas because the reflection coefficient for the intestinal vasculature is >0. Although the mucosal layer of the small intestine has a high blood flow both at rest and during food absorption, the capillary blood pressure is usually 13 to 18 mm Hg and seldom higher than 20 mm Hg during food absorption. Therefore, plasma colloidal osmotic pressure is higher than capillary blood pressure, favoring the absorption of water brought into the villi. During lipid absorption, the plasma protein reflection coefficient for the overall intestinal vasculature is decreased from a normal value of more than 0. It is assumed that most of the decrease in reflection coefficient occurs in the mucosal capillaries. This lowers the ability of plasma proteins to counteract capillary filtration, with the net result that fluid is added to the interstitial space. Not surprisingly, the highest rates of intestinal lymph formation normally occur during fat absorption. The intestinal vasculature is richly innervated by sympathetic nerve fibers and contains predominantly α -1 adrenoceptors. Thus, major reductions in gastrointestinal blood flow and venous volume occur whenever sympathetic nerve activity is increased, such as during strenuous exercise or periods of pathologically low arterial blood pressure. In particular, venoconstriction in the intestine during hemorrhage helps to mobilize blood to the central circulation and helps compensates for the blood loss. Gastrointestinal blood flow is about 25% of the cardiac output at rest; a reduction in this blood flow, by heightened sympathetic activity, allows more vital functions to be supported with the available cardiac output. However, in combination with a low arterial blood pressure (hypotension), gastrointestinal blood flow can be so drastically decreased by sympathetically mediated vasoconstriction that mucosal tissue damage can result. Nevertheless, this intestinal vasoconstriction can be seen as using the large size of the intestinal vasculature to the advantage of the body as a whole by providing a significant contribution of increased total peripheral vascular resistance to help counteract hypotension. In severe hypotension, perfusion to the heart and brain takes priority over that to other organs. The liver is primarily an organ that maintains the organic chemical composition of the blood plasma. For example, all plasma proteins are produced by the liver, and the liver adds glucose from stored glycogen to the blood. The liver also removes damaged blood cells and bacteria and detoxifies many man-made or natural organic chemicals that have entered the body. The hepatic circulation is perfused by gastrointestinal venous blood and hepatic arterial supply. It is perfused by both arterial blood through the hepatic artery and venous blood from the portal vein that has passed through the stomach, small intestine, pancreas, spleen, and portions of the large intestine. The venous blood arriving via the hepatic portal vein accounts for about 67% to 80% of the total liver blood flow (see Table 16. The majority of hepatic portal blood flow is determined by the flow through the stomach and small intestine. About half of the oxygen used by the liver is derived from venous blood, even though the splanchnic organs have removed one third to one half of the available oxygen. The liver has a high metabolic rate and is a large organ; consequently, it has the largest oxygen consumption of all organs in a resting person (see Chapter 27). The liver vasculature is arranged into subunits that allow the arterial and portal blood to mix and provide nutrition for the liver cells (Fig.
A similar situation can arise from scar tissue following pericarditis zudena 100 mg fast delivery erectile dysfunction treatment without drugs, in which inflamed pericardium eventually adheres to the epicardial tissue generic zudena 100mg on-line erectile dysfunction after vasectomy. This condition essentially wraps the heart in stiff tissue purchase zudena 100mg erectile dysfunction drugs over the counter, which then impedes stretch of the heart chamber with ventricular filling. However, the metabolism of glucose supplies about 20% of the heart’s energy needs, with the remaining needs supplied by the metabolism of lactate, pyruvate, amino acids, and certain ketones. Any index that could predict cardiac O demand under a variety of hemodynamic conditions would be2 invaluable to clinical medicine. Myocardial oxygen demand is one half of the important relationship between supply and demand of oxygen to the heart. Myocardial ischemia results whenever demand exceeds supply (see Chapters 15 and 16 for more details). For this reason alone, determination of oxygen demand by the heart is clinically valuable. However, a single index for determination of myocardial oxygen demand has yet to be found that is both clinically practical and universally applicable to all conditions that alter cardiac O demands. Nevertheless, in an effort to develop such an index, much has2 been learned about determinants of oxygen consumption by the heart. This information has proved invaluable to the management of cardiovascular disease and acute cardiovascular crises in the clinical setting. Increased afterload increases myocardial oxygen demand more than does increased preload, shortening, or inotropic state. The energy output of a system is classically defined as the sum of heat production and work. Work, in turn, is defined as a force acting through a distance, or work = force × distance. As applied to work done by the left ventricle, work is given as the product of stroke volume and either arterial pressure, ventricular pressure, or wall stress during systole. It can also be determined by the area circumscribed by the pressure–volume loop depiction of the cardiac cycle. In the heart, energy and, thus, oxygen must be used both to generate pressure and to pump blood (i. In would seem that determination of cardiac work would be one way in which the oxygen demand of the heart could be determined. To the contrary, work alone is a poor indicator of the magnitude of oxygen demand by the heart. Consider that in relation to the mathematics of basic physics, there is no distinction between whether a given quantity of cardiac work results from a large stroke volume ejected against a low pressure or a small stroke volume ejected against a high pressure; the same quantitative value of work would emerge. However, in the heart, much more O is2 required to generate force than to shorten. Thus, more oxygen is needed to meet increased work resulting from an increase in cardiac stress than from an increase in stroke volume. In other words, pumping against a high pressure is more oxygen costly, than pumping a high flow output, even if the total work is the same in both situations. Consequently, changes in cardiac work are poor quantitative indicators of myocardial oxygen demand. Beyond the basal O consumption needed to run membrane pumps and basic cellular activity2, four major determinants of increased O demand in the heart have been identified; these are (1) increased2 systolic pressure (or, more accurately, ventricular wall stress), (2) increased extent of muscle shortening (or stroke volume), (3) increased heart rate, and (4) positive inotropic stimuli. Combinations of hemodynamic variables have been used as estimators of O demand in the heart. The2 double product or systolic pressure × heart rate and the tension–time index (the area under the left ventricular systolic pressure curve) have been used as predictors of cardiac O demand. Changes in these2 indices reflect changes in the oxygen needs of the heart caused by changes in heart rate and force generation, but they often fail in instances in which certain drugs, such as β-adrenergic agonists, produce positive inotropic and chronotropic (heart rate) effects on the heart at the same time that their vasodilator effects cause a drop in blood pressure. Even without a good index available as a predictor of cardiac oxygen demand, it is useful to simply recognize factors proven to alter myocardial O demand. For example, hypertension, or high blood2 pressure, greatly increases the stress load on the heart and thus increases O demand. Similarly2, exercise increases heart rate, myocardial contractility, and, in unconditioned people, blood pressure as well, all of which synergize to create greatly increase myocardial O demand. In patients who have compromised2 coronary circulations resulting from atherosclerosis, it is thus helpful to realize that decreasing blood pressure and heart rate will lessen the possibility that cardiac oxygen demand will exceed cardiac oxygen supply. Ejection fraction and hemodynamic evaluations are used as simple clinical indices of myocardial performance. Clinical evaluation of the condition of the heart in patients is technologically demanding. Although many technologies and devices are available to evaluate the heart, their implementation requires specialized skills in cardiology. Nevertheless, there are some relatively simple means of estimating cardiac performance available to the clinician. Clinicians can obtain a two-dimensional view of changes in the size of the ventricular chambers during the cardiac cycle through the use of ultrasound images employed in echocardiography. Ventricular chamber cross-sectional area during systole and diastole can be estimated from these real-time images and used to estimate stroke volume in the heart. The change in areas between diastole and systole is expressed as a percentage of the area during diastole and is called the ejection fraction. In normal hearts, the ejection fraction is 45% to 67%; values ≤40% indicate impaired performance. Variables that reflect changes in the inotropic state of the heart have proven difficult to develop and are often used on the basis of what works reasonably well in the clinic. For example, the peak rate of rise of pressure in the left ventricle during isovolumic contraction (peak dP/dt) has been shown to reflect alterations in myocardial contractility and to be affected little by changes in preload or afterload. For example, the only way a patient’s stroke volume can decrease or remain unchanged in the face of an increased ventricular preload is if the patient’s heart is experiencing a negative inotropic influence. Conversely, increased stroke volume in the face of an unchanged or decreased preload indicates that the heart is under a positive inotropic influence. There are certain physiologic and pathologic conditions that are known to change loading conditions and the inotropic state of the heart. For example, drugs that relax venous smooth muscle lower central venous and ultimately right atrial pressure, thereby reducing the filling of the heart and ventricular preload. Standing causes pooling of blood in the lower extremities and also decreases pressure in the right atrium with a similar effect unless the body corrects for this by activation of sympathetic nerves to veins (see Chapter 17). However, drugs used to treat certain cardiovascular diseases such as hypertension and myocardial ischemia can counteract this corrective reflex by directly relaxing vascular smooth muscle. Such an effect in veins causes a drop in preload when the patient taking such medications rises from a supine to standing position.
Remember what any good marital therapist knows: each Another interesting clinical observation is how family person’s set of perceptions is absolutely real for them purchase 100 mg zudena visa erectile dysfunction lexapro. Perceptions are driven autonomy within the family and/or community or self- not by cold purchase 100mg zudena fast delivery erectile dysfunction just before intercourse, clear observation of obvious facts but by inter- advocacy buy zudena without prescription erectile dysfunction cholesterol lowering drugs. These hopes routines, roles, and rules or as potentially dangerous situ- must be dealt with gently and with respect. This may stem from fear for and protectiveness of least, do not immediately and offhandedly dismiss these the injured individual and from the many years of strug- hopes as unrealistic; it will be experienced as a crushing gling to establish a new family homeostasis. Many families have had ties, may lead to a need for further family restructuring experience with professionals who made pronouncements and education. Even Family Expectations in less severe cases, we really do not know what any given individual will be capable of-in both directions. Patients It is not uncommon for families to express goals, hopes, who look like they will make good recoveries languish; pa- and expectations for the person with the brain injury that, tients with severe impairments make achievements never The Family System 497 dreamed possible. Clinicians develop a set of expectations ents in a collaborative process of discovery to see how they on the basis of probabilities derived from experience. Some families, in the face of such explicit com- of deficit will not go back to work, then 5% will. How does parison (which they probably have never done), begin on one know if this family represents the exception and not their own to modify their expectations. Clinicians owe it to the family to keep their mit skepticism but are clear about wanting to move for- minds open. Other families may in fact be in full-blown denial- but again, contradicting them only fuels the denial (be- Principle #4: Never Underestimate Motivation. The process is then to families will succeed at what they put their minds to; it implement the first step with support, see how it goes, and does mean that clinicians should not short circuit the keep implementing steps as long as the person is succeed- power of families who have a strong need to achieve a goal ing. Ongoing monitoring and discussion are essential to until they have given themselves a chance to try. What assistance does she need on examina- the spirit of their goal, without necessarily endorsing the tions and papers? By breaking the “unrealis- down into steps and take one at a time, and find the spirit tic” goal down into steps, the professional can support of the goal and substitute reasonable alternatives. When it is in fact unrealis- practice, because families are often unrealistic about fu- tic, both the injured person and his or her family will grad- ture goals soon after brain injury, it is most often the case ually realize that and be more at peace with letting go of that the spirit of the goal is identified first and then broken the goal because they gave it their best shot. A bright (2) Find the spirit of the goal and substitute reasonable young woman in college had the (realistic) goal of becom- alternatives. Her parents believe it is still possible and satisfy the underlying need by substituting another, for her to succeed and want her to resume college and take more reasonable goal. The clinicians are ab- when an original goal has been broken down into steps and solutely convinced this is not possible. The girl had severe visual problems, severe motor in- saying, “Oh, you’re right, we never noticed that. Her fam- pectations express deep-seated needs and hopes on their ily was, at least superficially, supportive of her goals and part, coupled with a willingness to believe that recovery, told others of her plans. This engages the par- aspiration and the reconstruction of her self-esteem by 498 Textbook of Traumatic Brain Injury denying her a model with whom to identify. It could do occurs with persons with more severe injuries who have significant harm. However, the family, fully endorse the goal and reassure the girl that everyone in the desire to protect the vulnerable family member, fails will do everything possible to help her achieve that goal. This usually occurs with people with plications of her deficits, or both, and set her up for a par- frontal lobe injuries whose judgment may be compro- ticularly devastating failure. Such families may block students return to school after severe brain injury, there is a efforts at continuing education, job trials, dating, or inde- benign tendency to grade them by their effort, not their pendent travel or living. In this example, it is important that the grade A number of strategies may be helpful to the clinician in given the girl be a realistic one on the basis of the course ex- this case. Helping others, making suf- risks involved (how realistic the risks are and what steps fering go away, or enabling a person to learn and succeed may could be taken to minimize them), is often helpful. But exploring the spirit of the goal in search of an al- ery of what is realistically possible. Often, the reality is that the only forth explicitly as a compromise measure: it satisfies the way a family will confront the impossibility of a goal is to injured person’s desire to see how independent she can be- try it and fail. The key is to set up a safety net in the event come in travel while satisfying the family’s need to main- the person fails. Thus, the client might be guided give it a try,” then shrug your shoulders and walk away. Between each step, family members tingency plan if all comes crashing down are the respon- could be told how things went, and their consent could be sible clinical approaches. Then again-the introduce at each step a goal that has a high probability of patient might fool the clinician and succeed. The one exception to allowing controlled failure is Such an approach sidesteps the major conflict of whether when the cost of failure could be catastrophic in terms of the family will allow the injured person to travel alone and human or financial well-being. A trader responsible for introduces a stepwise process of gradual challenge in millions of dollars a day, an air traffic controller, or a sur- which the family is never asked to lose control of the pro- geon should not be let loose to “see what happens,” no cess. Allowing families to retain a sense of control and matter how reliable the safety net. However, even in high- safety in decisions about the injured person is a key con- risk situations, it is often possible to create a supervised, cept in dealing with unrealistic expectations. Doctors, for example, can perform limited The preceding principles are not all-inclusive. But when the are meant to represent some of the guidelines profession- cost of failure is potentially too high, the risk of uncon- als can use when confronted with families whose goals are trolled experimentation simply cannot be taken. The key is to join with the family to develop a process of moving toward a goal to discover Principle #7: Be Prepared to Challenge Overprotective how realistic it is or to see if it can be reshaped in some Families That Are Negatively Unrealistic. Simply telling the problem, but one that falls under the category of unrealis- family that goals are unrealistic almost never works. It tic families, is the overprotective family that underesti- does not deter family members, and clinicians lose their mates the capacities of the injured person. The Family System 499 likely), the parents will need to be the ones to initiate con- Special Issues tact with the school around the special needs of their child. When the child is nearing discharge refers to injuries with brief or no loss of consciousness, no home, the parents need to make sure the rehabilitation long-term focal neurological abnormalities, usually nor- team is putting together recommendations for school mal computed tomography scans and magnetic resonance needs and help the team contact the appropriate school imaging studies, and a constellation of symptoms, includ- personnel. Depending on the severity of the injury, the time time and increases dysfunction, which usually reflects a since injury, and the student’s stamina, the return to complex interaction among organic, personality, and envi- school may need to be gradual. In many cases, a legitimate, if subtle, take the lead in contacting the school to work out these de- brain injury underlies and drives the dysfunction, which cisions.
Upon release into the synaptic cleft order zudena american express impotence news, it is degraded by acetylcholinesterase back to choline and acetate buy on line zudena erectile dysfunction doctor boca raton. There are two main classes of cholinergic receptors: nicotinic and muscarinic receptors purchase zudena mastercard female erectile dysfunction drugs. Nicotinic receptors have subtypes that are located at the neuromuscular junction, autonomic ganglia, and central nervous system. Nicotinic receptors are ligand- gated ion channels that are permeable to sodium and calcium. The influx of sodium results in local membrane depolarization and can lead to the activation of voltage-gated sodium channels and the production of an action potential. Excess stimulation of these receptors can also result in a depolarizing blockade in which there is a sustained contraction of the muscle. M, M, and M receptors1 5 1 3 5 interact with G proteins and thus lead to activation of phospholipase C and the eventual increase inq intracellular calcium from intracellular stores along with activation of protein kinase C. M and M2 4 receptors interact with G proteins leading to decreased protein kinase A activation, hyperpolarization ofi the membrane due to the activation of certain potassium channels, and reduction in vesicular mobilization due to the closing of certain calcium channels. In addition to actions in the brain, muscarinic receptors are also the primary receptor of the parasympathetic nervous system. Agents that enhance cholinergic transmission in the brain by inhibiting acetylcholinesterase are currently approved for use in Alzheimer’s disease and may delay cognitive impairment in the initial stages of the disease. The catecholamines (dopamine, norepinephrine, and epinephrine) are all synthesized from a common precursor, tyrosine, and share a common synthetic pathway. When a monoamine oxidase inhibitor is combined with another drug that increases the levels of a particular monoamine, life-threatening situations can result: hypertensive crisis with norepinephrine and serotonin syndrome with serotonin. Norepinephrine can be further converted to epinephrine if the enzyme phenylethanolamine-N-methyltransferase is present. Most epinephrine is secreted from chromaffin cells of the adrenal medulla and circulates peripherally in response to activation of the sympathetic nervous system. It can then be taken back up into the presynaptic terminal by the norepinephrine transporter. There are two main receptor subtypes with which norepinephrine and epinephrine interact: alpha and beta adrenergic receptors. The α receptor activates the1 G protein, while the α receptor activates the G protein. There are three beta adrenergic receptors (β, β,1 2 and β ), which all activate G proteins. Certain stimulant drugs, like amphetamine and methamphetamine, also produce effects through activation of adrenergic receptors. Dopamine Dopamine was once thought to simply be the precursor for norepinephrine but now it is recognized as a neurotransmitter in its own right. It is involved in control of movement, reward and addiction, and development of schizophrenia. D and D receptors activate the G1 5 1 5 s protein, whereas D, D, and D receptors activate G proteins. Activation of dopaminergic receptors is2 3 4 i used clinically in the treatment of Parkinson’s disease. Inhibition of these receptors is used clinically in the treatment of schizophrenia and psychosis. Many addictive drugs and behaviors involve activation of the dopaminergic “reward pathway. Upon release into the synaptic cleft, it interacts with postsynaptic and presynaptic receptors. Its action is terminated via reuptake into the presynaptic terminal by the serotonin transporter. Clinicallys, serotonin reuptake inhibitors are used to treat depression by enhancing the levels of serotonin in the synaptic cleft. Agents that activate selective serotonin receptors are used clinically to treat migraines and anxiety. Agents that block serotonin receptors in the chemoreceptor trigger zone are used in the treatment of nausea and vomiting. It plays a role in learning and memory, pain transmission, epilepsy, and some forms of neurotoxicity. Glutamate in nerve terminals is converted from α-ketoglutarate, from the Krebs cycle, and stored in vesicles. It then undergoes calcium-dependent vesicular release into the synaptic cleft where it can interact pre- and postsynaptically with its receptors. Its action is terminated by uptake via an excitatory amino acid transporter back into the presynaptic terminal or into glial cells where it is converted to glutamine by the enzyme glutamine synthase. Glutamine can then leave the glial cell and enter the presynaptic terminal via the glutamine transporter. It is converted in the presynaptic terminal back to glutamate and then taken up into the vesicle via a vesicular glutamate transporter. The Ca permeability is thought to play a role in the toxicity associated with excess glutamate in the synaptic cleft. When the pore opens, these negatively charged ions enter the cell and lead to hyperpolarization thus decreasing the excitability of the cell. Inhibition of these receptors produce drowsiness, which is a side effect ofq antihistamines that cross the blood–brain barrier. These inhibitors of the H receptors have therapeutic1 utility in over-the-counter sleep aids. In the periphery, H receptor antagonists (“antihistamines”) are1 mainly used in treating allergic responses and in symptoms of colds and flu. It is stored in vesicles and often found in terminals that also contain norepinephrine. Effects of caffeine are mediated in part by the inhibition of certain adenosine receptors. Neuropeptide precursors are synthesized in the cell body where they are packaged into vesicles by the Golgi apparatus. The precursors are cleaved into smaller peptides by proteases within the vesicle as they are transported to the terminal. Generally, the neuropeptides are co-localized within the same presynaptic terminal with vesicles containing classical neurotransmitters. A strong stimulus can release both the neurotransmitter and neuropeptide into the synaptic cleft. Neuropeptides diffuse out of the synaptic cleft and are degraded by extracellular proteases. The endogenous compounds that activate these receptors are the neuropeptides endorphin, enkephalin, and dynorphin. Thus, opioids decrease synaptic transmission by hyperpolarizing the cell and decreasing calcium-mediated vesicular mobilization.
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