By T. Murak. University of Indianapolis.

It results from dysfunc- Language impairment may differ tion of the language centers in the brain generic 90 mg dapoxetine visa impotence 27 years old, depending on the area of the brain dam- rather than impairment in the muscu- aged 60mg dapoxetine with visa erectile dysfunction drugs medicare. Individuals may nitive skills: be able to understand and read simple material; however, as the complexity or • Memory length of the message increases, difficul- • Attention and concentration ty becomes more apparent. Although • Self-awareness they are able to comprehend, they may • Problem solving and decision making have difficulty expressing thoughts in • Information processing and concept speech and writing because of difficulty formation putting words and sentences together log- • Judgment ically. Speech may be labored, slow, and/or difficult to Memory encompasses the ability to understand, and small connecting words, store and retrieve information. Memory and increased verbal output, but with for both new and old information may be reduced information content, so that affected. Immediate memory lasts only sec- Wernicke’s aphasia are typically unaware onds or minutes unless converted in- of their communication difficulties. An example In some instances individuals may ex- of immediate memory is remember- perience global aphasia, in which there ing a phone number long enough to is severe difficulty communicating because dial the number, but then not com- of both the inability to use language (to mitting it to memory for later use. Short-term memory lasts from min- to wipe the same spot on a counter until utes to hours, but it is then lost if not someone intervenes. An Individuals with brain damage may be example of short-term memory may unable to remember skills that were once be learning facts for a test but not very familiar. For instance, they may be committing the facts to long-term unable to complete simple daily tasks, memory for continued use. Long-term memory is memories that to remember the steps involved or are stored and are able to be retrieved because, after completing the first steps of in the future, whether after weeks or the task, they forget their original goal. Memory problems can be the most lim- iting of all of the potential cognitive con- A variety of memory problems may be sequences of brain damage because they experienced after brain damage. Some affect the individual’s ability to learn, individuals may be able to remember facts store, and retrieve information. The abil- but are unable to remember how to do ity to profit from experience is often specific tasks. Consequently, individuals may be able to remember the names and may continue to make the same mistakes birthdates of family members but be un- over and over, since the ability to apply able to remember how to operate a wash- what was learned from past experience is ing machine. The ability to gener- retrograde amnesia in which they are alize from one situation to another may unable to remember things that occurred also be impaired. For example, an ments may have forgotten their own per- individual who has learned a skill in a sonal history so they do not recognize rehabilitation setting may be unable family members, or they may not be able to perform that skill in his or her own to remember what type of work they had home. After brain damage individuals can Attention and Concentration have difficulty remembering or learning new information so that they are unable After brain damage individuals may find to acquire new memories or recall recent it difficult to focus attention and to con- conversations and events. Conse- stances individuals make up answers to quently, they may be unable to follow a questions, or make up situations or events train of thought or perform multiple step (confabulation). They may have difficulty faulty memory but from the tendency to focusing on one task, may be easily dis- juxtapose unrelated memories together. At tracted, or may be unable to “shift gears” other times, in conversation, individuals from one task to another. Individuals with may get stuck on one theme, repeating a brain damage may find it difficult to per- question, phrase, or concept again and form multiple tasks at one time, such as again (perseveration). Perseveration can writing down messages or notes while also pertain to tasks that the individual talking on the phone, or carrying on a repeats over and over, such as continuing conversation while polishing furniture. For example, if they want to visit a friend in another city, they may recog- Individuals with brain damage may nize that they can take a train to get there, have limited ability to recognize or under- but they may not be able to consider how stand the limitations they are experienc- they would obtain money for the train ing. They may lack insight into the fare, how they would obtain a ticket, or appropriateness of their behavior and may how they would get to the train station. There may also be an inability to There may also be lack of ability to ini- monitor and adjust their own actions tiate and sustain activity. When become inconsistent, so that tasks per- they do receive feedback, they may dis- formed well on one day may not be count it because they disagree with oth- performed well on subsequent days. Indi- ers’ observations regarding their behavior viduals with damage to the left side of the or performance. When presented with a new Problem Solving and Decision Making problem, they may respond slowly and in a cautious, disorganized fashion. In most Planning and organizing and therefore instances, it is helpful to divide tasks into problem solving may be difficult after smaller steps to avoid confusion. For example, when preparing throughout even simple tasks such as a meal, individuals may not recognize that dressing to be assured that the task is food items that take more time to cook being performed correctly. Consequently, they may fully prepare the mashed pota- Information Processing toes before even starting to make the meatloaf. In other instances individuals Even when hearing and vision are un- may have difficulty following steps in impaired, more time may be needed to order. There may put on their slacks before they put on may be delayed response to visual and/or underwear or put their socks on over their verbal stimuli, so that individuals may shoes. In some instances comprehension problems as they occur, and if a problem of input itself may be severely disrupted. Individuals may but also in the ability to sequence and cat- consider only immediate information egorize information, so that there is diffi- rather than looking at the situation as a culty understanding concepts. As a result, Conditions Affecting the Brain 45 abstraction may be difficult, and individ- • Apathy and depression uals may tend to think only in concrete • Loss of self-esteem terms and cues and stimuli may be taken literally.

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The increase in blood flow down this region is primarily a • Blood flow shows about a 5-fold difference between the result of capillary distension generic dapoxetine 60mg line erectile dysfunction treatment calgary. This causes gravity-dependent regional variations in the V˙ A/Q ratio that range from 0 order 90 mg dapoxetine with amex erectile dysfunction drugs class. Blood flow is pro- Are Not Always Matched in the Lungs portionately greater than ventilation at the base, and Thus far, we have assumed that if ventilation and cardiac ventilation is proportionately greater than blood flow at output are normal, gas exchange will also be normal. Even though total ventila- The functional importance of lung ventilation-perfu- tion and total blood flow (i. The distribution of V˙ A/Q˙ in a healthy adult is shown in cardiac output is not fully oxygenated. Even in healthy lungs, most of the ventila- tion and perfusion go to lung units with a V˙ A/Q˙ ratio of by considering the ventilation-perfusion ratio, which com- pares alveolar ventilation to blood flow in lung regions. At the apical re- gion, where the V˙ A/Q˙ ratio is high, there is overventila- Since resting healthy individuals have an alveolar ventila- tion (V˙ A) of 4 L/min and a cardiac output (pulmonary blood tion relative to blood flow. At the base, where the ratio is flow or perfusion) of 5 L/min, the ideal alveolar ventilation- low, the opposite occurs (i. We have already seen that gravity can passes through the pulmonary capillaries at the base of the cause regional differences in blood flow and alveolar venti- lungs without becoming fully oxygenated. The effect of regional V˙ A/Q˙ ratio on blood gases is lation (see Chapter 19). In an upright person, the base of the lungs is better ventilated and better perfused than the apex. Because overventilation relative to blood flow (high V˙ A/Q) occurs in the apex, the P˙ AO is high Regional alveolar ventilation and blood flow are illus- 2 trated in Figure 20. Three points are apparent from this and the PACO2 is low at the apex of the lungs. Oxygen ten- figure: sion (PO2) in the blood leaving pulmonary capillaries at the • Ventilation and blood flow are both gravity-dependent; base of the lungs is low because the blood is not fully oxy- airflow and blood flow increase down the lung. The ventilation-perfu- sion ratio is shown on the x-axis, plotted on a logarithmic scale. Gravity causes a mismatch of blood flow and alveolar ventilation in the base and apex of the lungs. At the base of the lungs, blood flow exceeds alveolar ventilation, resulting in a low ventilation-perfusion ratio. At the apex, the opposite occurs; alveolar ventilation is greater than blood flow, resulting in a high ventilation-perfusion ratio. Regional differences in V˙ A/Q˙ ratios tend to localize some diseases to the top or bottom parts of the lungs. For example, tuberculosis tends to be localized in the apex be- cause of a more favorable environment (i. SHUNTS AND VENOUS ADMIXTURE Matching of the lung’s airflow and blood flow is not per- fect. On one side of the alveolar-capillary membrane there is “wasted air” (i. CHAPTER 20 Pulmonary Circulation and the Ventilation-Perfusion Ratio 347 PIO = 148 mm Hg PEO2 = 118 mm Hg 2 PICO = 0 mm Hg PECO2 = 29 mm Hg 2 "Wasted air" Inspired Expired gas c gas Alveolar gas PO2 = 102 mm Hg End-pulmonary PCO2 = 40 mm Hg capillary blood Alveolar-capillary membrane PO2 = 102 mm Hg PCO2 = 40 mm Hg FIGURE 20. On one side there is “wasted air” Mixed Systemic and on the other side there is “wasted blood. There are two causes for ve- alveolar capillaries is not completely oxygenated. A low regional A/ ratio when blood bypasses alveoli through a channel, such as can also occur with a partially obstructed airway (Fig. An anatomic shunt blood passing through a hypoventilated region is not fully is often called a right-to-left shunt. The bronchial circula- oxygenated, resulting in an increase in venous admixture. This occurs when a portion of the cardiac out- analogous to physiological dead space; the two are com- put goes through the regular pulmonary capillaries but pared in Table 20. With a low regional V˙ A/Q˙ ratio, there is remember that, in healthy individuals, there is some de- Normal Local low VA/Q Local high VA/Q PAO2 = 102 mm Hg PAO2 < Normal PAO2 > Normal PACO2 = 40 mm Hg PACO2 > Normal PACO2 < Normal FIGURE 20. Airway obstruc- tion (middle panel) causes a low regional ventila- tion-perfusion (V˙ A/Q) ratio. A partially blocked˙ airway causes this region to be underventilated relative to blood flow. A low regional V˙ A/Q ratio causes˙ venous admixture and will increase the physio- logical shunt. A partially obstructed pulmonary arteriole (right panel) will cause an abnormally high V˙ A/Q ratio in a lung region. Restricted˙ PO = 40 mm Hg PO = 40 mm Hg blood flow causes this region to be overventi- 2 2 PO2 = 40 mm Hg lated relative to blood flow, which leads to an in- PCO2 = 46 mm Hg PCO2 = 46 mm Hg PCO2 = 46 mm Hg crease in physiological dead space.

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Similarly cheap dapoxetine 90mg without a prescription erectile dysfunction at age 20, glucagon promotes the net lipase Fatty acids breakdown of glycogen by promoting the inactivation of Fatty glycogen synthase (Fig buy 60mg dapoxetine with mastercard erectile dysfunction protocol book review. In addition to promot- ing hepatic glucose production by stimulating glycogenol- FIGURE 35. Insulin promotes the accumulation ysis, glucagon stimulates hepatic gluconeogenesis (Fig. It does this principally by increasing the transcrip- shown by the heavy arrows and inhibiting the processes shown tion of mRNA coding for the enzyme phosphoenolpyru- by the light arrows. Similar stimulatory and inhibitory effects oc- vate carboxykinase (PEPCK), a key rate-limiting enzyme in cur in liver cells. Glucagon also stimulates amino acid CHAPTER 35 The Endocrine Pancreas 629 Glucose Glycogen α-Glycerol phosphate Glycogen Glycogen synthase phosphorylase Triglycerides Glucose Glucose Glucose 6- phosphate Acetyl CoA Fatty Hormone- acids sensitive Ketogenesis lipase Ketones Glycerol LIVER CELL FIGURE 35. Heavy ar- rows indicate processes stimulated by glucagon; light arrows indi- cate processes inhibited by glucagon. Ketones Fatty acids transport into liver cells and the degradation of hepatic proteins, helping provide substrates for gluconeogenesis. The glucagon-enhanced The role of glucagon in lipolysis and keto- FIGURE 35. Glucagon assists in the disposal of processes stimulated by glucagon; light arrows indicate processes ammonia by increasing the activity of the urea cycle en- inhibited by glucagon. Ketones are an important Amino source of fuel for muscle cells and heart cells during times of acids starvation, sparing blood glucose for other tissues that are obligate glucose users, such as the central nervous system. During prolonged starvation, the brain adapts its metabolism to use ketones as a fuel source, lessening the overall need for hepatic glucose production (see Chapter 34). Protein synthesis Gluconeo- The Insulin-Glucagon Ratio Determines genesis Amino Metabolic Status Glucose Protein acids In most instances, insulin and glucagon produce opposing effects. Therefore, the net physiological response is deter- Ammonia Protein mined by the relative levels of both hormones in the blood degradation plasma, the insulin-glucagon ratio (I/G ratio). The I/G ratio Urea may vary 100-fold or more because the plasma concentra- tion of each hormone can vary considerably in different nu- tritional states. After an overnight fast, it may fall to about 2, and with prolonged fasting, it may fall to as low as 0. LIVER CELL The role of glucagon in gluconeogenesis Inappropriate I/G Ratios in Diabetes. Heavy arrows the profound influence of the I/G ratio on metabolic status indicate processes stimulated by glucagon; light arrow indicates is in insulin-deficient diabetes. The specific environmental factors have not been secretion of glucagon is inappropriately elevated. Because the primary defect in type 1 diabetes is the in- ability of beta cells to secrete adequate amounts of insulin, these patients must be treated with injections of insulin. In DIABETES MELLITUS an attempt to match insulin concentrations in the blood Diabetes mellitus is a disease of metabolic dysregulation— with the metabolic requirements of the individual, various most notably a dysregulation of glucose metabolism—ac- formulations of insulin with different durations of action companied by long-term vascular and neurological complica- have been developed. Diabetes has several clinical forms, each of which has a amount of these different insulin forms to match their di- distinct etiology, clinical presentation, and course. Diabetes is the most common endocrine dis- tients are advised to monitor their diet and level of physical order. Some 16 million people may have the disease in the activity, as well as their insulin dosage. Exercise per se, United States; the exact number is not known because many much like insulin, increases glucose uptake by muscle. Symptoms usually include frequent urination, increased thirst, increased food consumption, and weight loss. The Type 2 Diabetes Mellitus Primarily Originates standard criterion for a diagnosis of diabetes is an elevated in the Target Tissue plasma glucose level after an overnight fast on at least two Type 2 diabetes mellitus results primarily from impaired separate occasions. In some cases, it is a permanent, lifelong disorder; in causes, symptoms, and general medical outcomes are vari- others, it results from the secretion of counterregulatory able. Generally, the disease takes one of two forms, type 1 hormones in a normal (e. Women who have had gestational diabetes have an increased risk of developing type 2 dia- Most Forms of Type 1 Diabetes Mellitus betes later in life. Involve an Autoimmune Disorder Type 1 diabetes is characterized by the inability of beta Insulin Resistance in Type 2 Diabetes. In most cases of cells to produce physiologically appropriate amounts of in- type 2 diabetes, normal or higher-than-normal amounts of sulin. In some instances, this may result from a mutation in insulin are present in the circulation. However, the most common form impairment in the secretory capacity of pancreatic beta of type 1 diabetes results from destruction of the pancreatic cells but only in the ability of target cells to respond to in- beta cells by the immune system. In some instances, it has been demonstrated that the event is insulitis, involving a lymphocytic attack on beta fundamental defect is in the insulin receptor.

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In this procedure order 60 mg dapoxetine overnight delivery erectile dysfunction pump how do they work, the semen is diluted with a 10% glycerol buy generic dapoxetine 60 mg on line erectile dysfunction without pills, monosaccharide, and distilled water of Semen buffer, and frozen in liquid nitrogen. For some unknown reason, however, not all human sperm is suitable for freezing. Explain the statement that male sexual function is an auto- 1 hour after ejaculation 70% or more nomic synergistic action. Use a flow chart to explain the physiological and physical Leukocyte count 0–2,000/ml events of erection, emission, and ejaculation. Fructose concentration 150–600 mg/100 ml Reprinted with permission of Medical Economics Company from Glaser, L. CLINICAL CONSIDERATIONS Sexual dysfunction is a broad area of medical concern that in- cludes developmental and psychogenic problems as well as con- spurts of semen from the ejaculatory ducts and the urethra. Psychogenic problems of takes place as parasympathetic impulses traveling through the pu- the reproductive system are extremely complex and beyond the dendal nerves stimulate the bulbospongiosus muscles (see fig. Only a few of the principal developmental at the base of the penis and cause them to contract rhythmically. Sexual function in the male thus requires the synergistic action (rather than antagonistic action) of the parasympathetic and sympathetic divisions of the ANS. The mechanism of emis- Developmental Problems of the Male sion and ejaculation is summarized in figure 20. Immediately following ejaculation or a cessation of sexual Reproductive System stimulus, sympathetic impulses cause vasoconstriction of the ar- The reproductive organs of both sexes develop from similar em- terioles within the penis, reducing the inflow of blood. At the bryonic tissue that follows a consistent pattern of formation well same time, cardiac output returns to normal, as does venous re- into the fetal period. Because an embryo has the potential to dif- turn of blood from the penis. With the normal flow of blood ferentiate into a male or a female, developmental errors can re- through the penis, it returns to its flaccid condition. A person with undifferentiated or am- spontaneous emission and ejaculation of semen during biguous external genitalia is called a hermaphrodite. These nocturnal emissions, sometimes called “wet dreams,” True hermaphroditism—in which both male and female are triggered by psychic stimuli associated with dreaming. They are thought to be caused by changes in hormonal concentrations that gonadal tissues are present in the body—is a rare anomaly. Male pseudohermaphroditism occurs more frequently and generally results from hormonal influences during early fetal Semen development. This condition is caused either by inadequate se- Semen, also called seminal fluid, is the substance discharged dur- cretion of androgenic hormones or by the delayed development ing ejaculation (table 20. These individuals have a 46 XY chromosome con- (about 60%) is produced by the seminal vesicles, and the rest stitution and male gonads, but the genitalia are intersexual and (about 40%) is contributed by the prostate. There are usually between 60 and 150 million sperm cells per milliliter of ejaculate. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 Chapter 20 Male Reproductive System 715 The treatment of hermaphroditism varies, depending on the extent of ambiguity of the reproductive organs. Although people with this condition are sterile, they may engage in normal Pelvic sexual relations following hormonal therapy and plastic surgery. The two most 3 Symphysis frequent chromosomal anomalies cause Turner’s syndrome and pubis Klinefelter’s syndrome. About 97% of embryos lacking an X chromosome die; the remaining 3% survive and appear to be Penis females, but their gonads, if present, are rudimentary and do not Scrotum mature at puberty. A person with Klinefelter’s syndrome has an XXY chromosome constitution, develops breasts and male geni- (a) Creek talia, but has underdeveloped seminiferous tubules and is gener- ally mentally retarded. A more common developmental problem than genetic ab- normalities, and fortunately less serious, is cryptorchidism. A cryptorchid testis is usually located along the path of descent but can be anywhere in the pelvic cavity 1 (fig. It occurs in about 3% of male infants and should be treated before the infant has reached the age of 5 to reduce the likelihood of infertility or other complications. The causes of impotence may be physical, involving, for example, ab- normalities of the penis, vascular irregularities, neurological dis- Pelvic cavity orders, or certain diseases. Occasionally, the cause of impotence 1 is psychological, and the patient requires skilled counseling by a sex therapist. The most common 3 cause of male infertility is inadequate production of viable sperm. This may be due to alcoholism, dietary deficiencies, local injury, Penis variococele, excessive heat, hormonal imbalance, or excessive exposure to radiation. Many of the causes of infertility can be Scrotum treated through proper nutrition, gonadotropic hormone treat- (c) ment, or microsurgery. If these treatments are not successful, it may be possible to concentrate the spermatozoa obtained FIGURE 20.

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The mecha- equipped with receptors that bind hormones with high nism is usually negative feedback dapoxetine 60 mg without a prescription erectile dysfunction treatment in mumbai, although a few positive affinity and specificity; when bound order dapoxetine 90 mg with mastercard erectile dysfunction meds at gnc, they initiate charac- feedback mechanisms are known. Both types of feedback teristic biological responses by the target cells. Although many hormones travel by just its rate of hormone secretion to produce the desired this mechanism, we now realize that there are many hor- level of effect, ensuring the maintenance of homeostasis. Since negative feedback is their target cells by diffusion through the interstitial fluid. First-order feedback regulation Hormone Receptors Determine Whether a is the simplest type and forms the basis for more complex Cell Will Respond to a Hormone modes of regulation. In this example, an endocrine cell se- In the endocrine system, a hormone molecule secreted cretes a hormone that produces a specific biological effect into the blood is free to circulate and contact almost any in its target tissue. As the biological response in- that possess specific receptors for the hormone, will re- creases, the amount of hormone secreted by the endocrine spond to that hormone. More commonly, feedback biological effects characteristic of that hormone are initi- regulation in the endocrine system is complex, involving ated. Therefore, in the endocrine system, the basis for second- or third-order feedback loops. For example, multi- specificity in cell-to-cell communication rests at the level ple levels of feedback regulation may be involved in regu- of the receptor. Similar concepts apply to autocrine and lating hormone production by various endocrine glands un- paracrine mechanisms of communication. The A certain degree of specificity is ensured by the re- regulation of target gland hormone secretion, such as adre- stricted distribution of some hormones. For example, sev- nal steroids or thyroid hormones, begins with production eral hormones produced by the hypothalamus regulate of a releasing hormone by the hypothalamus. These hor- hormone stimulates production of a trophic hormone by mones are carried via small blood vessels directly from the the anterior pituitary, which, in turn, stimulates the pro- hypothalamus to the anterior pituitary, prior to entering duction of the target gland hormone by the target gland. In addition, the trophic hormone may inhibit the distribution of active hormone is the local transforma- releasing hormone secretion from the hypothalamus, and tion of a hormone within its target tissue from a less active in some cases, the releasing hormone may inhibit its own to a more active form. Dihydrotestos- to provide certain advantages compared with the simpler sys- terone is a much more potent androgen than testosterone. Theoretically, it permits a greater degree of fine-tuning Because the enzyme that catalyzes this conversion is found of hormone secretion, and the multiplicity of regulatory steps only in certain locations, its cell or tissue distribution minimizes changes in hormone secretion in the event that partly localizes the actions of the androgens to these sites. Therefore, while receptor distribution is the primary fac- It is important to bear in mind the normal feedback rela- tor in determining the target tissues for a specific hor- tionships that control the secretion of each individual hor- mone, other factors may also focus the actions of a hor- mone are discussed in the chapters that follow. Endocrine Target cell cell Signal Amplification Is an Important Characteristic of the Endocrine System Another important feature of the endocrine system is signal amplification. Blood concentrations of hormones are ex- 9 12 ceedingly low, generally, 10 to 10 mol/L. Even at the 9 Biological effect higher concentration of 10 mol/L, only one hormone molecule would be present for roughly every 50 billion wa- ter molecules. Therefore, for hormones to be effective reg- B ulators of biological processes, amplification must be part of the overall mechanism of hormone action. Hypothalamus Amplification generally results from the activation of a se- ries of enzymatic steps involved in hormone action. At each Releasing hormone step, many times more signal molecules are generated than were present at the prior step, leading to a cascade of ever- increasing numbers of signal molecules. The self-multiplying nature of the hormone action pathways provides the molec- Anterior ular basis for amplification in the endocrine system. For ex- ample, insulin exhibits pleiotropic effects in skeletal mus- cle, where it stimulates glucose uptake, stimulates glycoly- sis, stimulates glycogenesis, inhibits glycogenolysis, Target gland stimulates amino acid uptake, stimulates protein synthesis, hormone and inhibits protein degradation. In addition, some hormones are known to have different effects in several different target tissues. For example, testos- Biological effect terone, the male sex steroid, promotes normal sperm forma- tion in the testes, stimulates growth of the accessory sex Simple and complex feedback loops in the glands, such as the prostate and seminal vesicles, and pro- FIGURE 31. B, A complex, multilevel feedback loop: the hy- istics, such as beard growth and deepening of the voice. Solid lines indicate stim- Multiplicity of regulation is also common in the en- ulatory effects; dashed lines indicate inhibitory, negative-feed- docrine system. For example, liver glycogen metabolism may be regulated hormone-effector pairs relative to normal feedback rela- or influenced by several different hormones, including in- tionships. For example, in the case of anterior pituitary hor- sulin, glucagon, epinephrine, thyroid hormones, and adre- mones, measuring both the trophic hormone and the target nal glucocorticoids. Furthermore, most dynamic tests of en- docrine function performed clinically are based on our The secretion of any particular hormone is either stimu- knowledge of these feedback relationships. Dynamic tests lated or inhibited by a defined set of chemical substances in 570 PART IX ENDOCRINE PHYSIOLOGY CLINICAL FOCUS BOX 31. In one test, a ter 32, the hormone plays a role in regulating bone growth bolus of arginine, which is known to stimulate growth hor- and energy metabolism in skeletal muscle and adipose tis- mone secretion, is given and a blood sample is taken a sue.

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