By K. Gnar. Long Island University. 2018.

Insulin has multiple individual actions in transporters are expressed in different tissues and generic suhagra 100mg with mastercard erectile dysfunction treatment vancouver, in some each of these tissues purchase suhagra 100 mg visa erectile dysfunction treatment drugs, the net result of which is fuel storage. GLUT 4, the insulin-stimulated glucose transporter, is Mechanism of Insulin Action. Although insulin was one of the primary form of the transporter present in skeletal mus- the first peptide hormones to be identified, isolated, and cle tissue and adipose tissue. It is present in plasma mem- characterized, its exact mechanism of action remains elusive. In tar- The insulin receptor is a heterotetramer, consisting of a pair get cells, the effect of insulin is to promote the of / subunit complexes held together by disulfide bonds translocation of GLUT 4 transporters from the intracellular (Fig. The subunit is an extracellular protein contain- pool into plasma membranes. As a result, more transporters ing the insulin-binding component of the receptor. The are available in the plasma membrane, and glucose uptake subunit is a transmembrane protein that couples the extra- by target cells is, thereby, increased. Activation of the subunit of the insulin receptor results Insulin and the Synthesis of Glycogen. Besides promot- in autophosphorylation, involving the phosphorylation of ing glucose uptake into target cells, insulin promotes its a few selected tyrosine residues in the intracellular portion storage. This event further activates the tyrosine ki- mary forms: as glycogen and (by metabolic conversion) as nase portion of the subunit, leading to tyrosine phospho- triglycerides. Glycogen is a short-term storage form that rylation of specific intracellular substrates. A cascade of plays an important role in maintaining normal blood glu- events follows, leading to the pleiotropic actions of insulin cose levels. While tyrosine phosphorylation events and skeletal muscle; other tissues, such as adipose tissue, appear to be the early steps in insulin action, serine/threo- also store glycogen but in quantitatively small amounts. In- nine phosphorylation or dephosphorylation is involved in sulin promotes glycogen storage primarily through two en- many of the final steps of insulin action. It activates glycogen synthase by pro- moting its dephosphorylation and concomitantly Insulin and Glucose Transport. Perhaps one of the most inactivates glycogen phosphorylase, also by promoting its important functions of insulin is to promote the uptake of dephosphorylation. A specific cell mem- brane carrier is involved but no energy is required, and the Insulin and Glycolysis. In adipose tissue and liver tissue, insulin promotes lipogenesis and in- hibits lipolysis (Fig. Insulin has similar actions in SS muscle, but since muscle is not a major site of lipid storage, the discussion here focuses on actions in adipose tissue and the liver. By promoting the flow of intermediates through S S glycolysis, insulin promotes the formation of -glycerol S S phosphate and fatty acids necessary for triglyceride forma- Extracellular tion. In addition, it stimulates fatty acid synthase, leading directly to increased fatty acid synthesis. Insulin inhibits the breakdown of triglycerides by inhibiting hormone-sen- sitive lipase, which is activated by a variety of counterreg- ulatory hormones, such as epinephrine and adrenal gluco- corticoids. By inhibiting this enzyme, insulin promotes the Intracellular β subunit accumulation of triglycerides in adipose tissue. The insulin receptor is a heterotetramer consisting adipose tissue, insulin increases the activity of lipoprotein of two extracellular insulin-binding subunits linked by disulfide lipase, which plays a role in the uptake of fatty acids from bonds to two transmembrane subunits. As a result, lipoproteins syn- an intrinsic tyrosine kinase that is activated upon insulin binding thesized in the liver are taken up by adipose tissue, and to the subunit. Insulin promotes the ac- cumulation of protein by stimulating (heavy arrows) amino acid Citric acid cycle uptake and protein synthesis and by inhibiting (light arrows) pro- tein degradation in liver, skeletal muscle, and adipose tissue. Insulin promotes glucose uptake into target tissues, stimulates glycogen synthesis, synthesis. Insulin also increases the amount of protein syn- and inhibits glycogenolysis. In addition it promotes glycolysis in thesis machinery in cells by promoting ribosome synthesis. Heavy arrows indicate processes stimulated by Third, insulin inhibits protein degradation by reducing lyso- insulin; light arrows indicate processes inhibited by insulin. Effects of Insulin on Protein Synthesis and Protein Degra- Glucagon Primarily Affects the Liver Metabolism dation. Insulin promotes protein accumulation in its pri- of Carbohydrates, Lipids, and Proteins mary target tissues—liver, adipose tissue, and muscle—in The primary physiological actions of glucagon are exerted three specific ways (Fig. Second, it increases the activity of several factors in- mented in other tissues, primarily adipose tissue, when the volved in protein synthesis.

Prior to death discount 100 mg suhagra mastercard erectile dysfunction treatment washington dc, most of these people have impaired cardiac function as a result of coronary artery disease buy generic suhagra 100mg erectile dysfunction prevention, lead- 100 ing to heart failure with decreased quality of life. Progres- sive occlusion of coronary arteries by atherosclerotic plaques and acute occlusion as a result of the formation of blood clots in damaged coronary arteries are life-threaten- ing because the metabolic needs of the cardiac muscle can no longer be met by the blood flow. Because the plaque or clot partially occludes the vessel lumen, vascular resistance is increased, and blood flow would decrease if smaller coro- nary vessels did not dilate to restore a relatively normal blood flow at rest. In doing so, the reserve for dilation of 0 these vessels is compromised. While this usually has no ef- fect at rest, when cardiac metabolism is increased, the de- 50 creased ability to increase blood flow can limit cardiac per- formance. In many cases, inadequate blood flow is first noticed as chest pain—known as angina pectoris—origi- nating from the heart, and a feeling of shortness of breath during exercise or work. The vascular occlusion can cause 0 conditions ranging from impaired contractile ability of the 0. Note that left coronary artery blood flow decreases dramati- be used to cause coronary vasodilation or decreased car- cally during the isovolumetric phase of systole, prior to opening diac work, or both. Left coronary artery blood flow remains lower normal, various approaches are used to lower the blood during systole than during diastole because of compression of the pressure, decreasing the heart’s workload and oxygen coronary blood vessels in the contracting myocardium. The left ventricle receives most of its arterial blood inflow during diastole. In addition to pharmacological treatment, mild to Right coronary artery blood flow tends to be sustained during moderate exercise, depending on the status of the coro- both systole and diastole because lower intraventricular pressures nary disease, is often advised. Aerobic exercise stimulates are developed by the contracting right ventricle, resulting in less the development of collateral vessels in the heart, im- compression of coronary blood vessels. Systemic and coronary energetics in the tem, and increases the efficiency of the body during work resting unanesthetized dog. Phasic right coronary artery blood flow in output needed for a given task, thereby decreasing the conscious dogs with normal and elevated right ventricular pres- heart’s metabolic energy requirement. This, in turn, leads to dilatory stimuli that po- have been shown to greatly slow and even slightly reverse tentially could overcome vasoconstriction. The goal is to lower blood lev- The overall concept evolving from both human and els of low-density lipoproteins (LDLs), which are known animal studies is that the sympathetic nervous system to accelerate the formation of cholesterol-containing ar- suppresses the decrease in coronary vascular resistance terial plaques. The LDL concentration should typically be during exercise despite the metabolic effects of epineph- lowered below 120 mg/dL, but some cardiologists favor rine mentioned. The partial constriction of large coro- lowering levels below 100 mg/dL. For most people, re- nary arterioles and most arteries by norepinephrine ap- ductions in LDL below 120 mg/dL are not attainable with pears to limit the retrograde flow of blood during diet and exercise. In those persons, drugs, known as ventricular systole and, in doing so, prevents part of the statins, which block the formation of cholesterol in the decreased flow in the deep layers of the heart wall. In ef- liver, appear to be highly effective in decreasing the risk fect, the body trades a small decrease in flow, relative to and severity of coronary artery disease. Simultaneous CHAPTER 17 Special Circulations 279 treatment with an aerobic exercise program and large CEREBRAL CIRCULATION amounts of niacin, to increase high-density lipoproteins The ultimate organ of life is the brain. Even the determina- (HDLs), may help the body remove cholesterol for pro- tion of death often depends upon whether or not the brain cessing in the liver. The most common cause of brain injury is some form of impaired brain blood flow. Such problems can de- Collateral Vessels Interconnect Sections velop as a result of accidents to arteries in the neck or brain, of the Cardiac Microvasculature occlusion of vessels secondary to atherosclerotic processes, and, surprisingly frequently, aneurysms that occur as a re- One of the likely contributing factors to compensate for sult of vessel wall tearing. Fortunately, treatment of these slowly developing coronary vascular disease is the enlarge- problems is constantly improving. In the healthy heart of a sedentary person, collateral arterial Brain Blood Flow Is Virtually Constant vessels are rare, but arteriolar collaterals (internal diameter, Despite Changes in Arterial Blood Pressure 100 m) do occur in small numbers. The expansion of The cerebral circulation shares many of the physiological existing collateral vessels and the limited formation of new characteristics of the coronary circulation. The heart and collaterals provide a partial bypass for blood flow to areas brain have a high metabolic rate (see Table 17. In part, the greater collateral en- vessels have a limited ability to constrict in response to largement in the endocardium compared to the epicardium sympathetic nerve stimulation. As described in Chapter 16, may be due to the lower pressure and blood flow in reach- the brain and coronary vasculatures have an excellent abil- ing the endocardial vessels. However, periods of inade- ture of the brainstem exhibits the most precise autoregula- quate blood flow to the heart muscle caused by experimental tion, with good but less precise regulation of blood flow in flow reduction do stimulate collateral enlargement in healthy the cerebral cortex. It is assumed that in humans with coronary vascular tory ability has clinical implications because the region of disease who develop functional collateral vessels, the mech- the brain most likely to suffer at low arterial pressure is the anism is related to occasional or even sustained periods of in- cortex, where consciousness will be lost long before the au- adequate blood flow. Whether or not routine exercise aids in tomatic cardiovascular and ventilatory regulatory functions the development of collaterals in healthy humans is debat- of the brainstem are compromised. However, there is no doubt that cal that causes cerebral autoregulation has not been possible. States will, at some time during their lifetimes, require Despite, the multiple treatments available to deal with ex- medical or surgical intervention because of atherosclero- isting coronary artery blockage, the ideal treatment is to avoid sis of the coronary arteries. Excessive intake of cholesterol-rich food, seden- rupture of the endothelial layer over an atherosclerotic tary lifestyles that tend to raise low-density lipoproteins (LDL) plaque, followed by a clot that occludes or nearly oc- and lower high-density lipoproteins (HDL), and obesity lead- cludes a coronary artery.

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Developmental © The McGraw−Hill Anatomy cheap suhagra 100mg otc erectile dysfunction grand rapids mi, Sixth Edition Development Anatomy generic suhagra 100 mg with mastercard erectile dysfunction low testosterone treatment, Postnatal Companies, 2001 Growth, and Inheritance 776 Unit 7 Reproduction and Development Symphysis pubis Urethra Ruptured Urinary amniotic Placenta bladder sac Vagina Cervix Rectum (a) (b) Placenta Uterus Umbilical cord Placenta (c) (d) FIGURE 22. Neonatal Period Most full-term newborn babies appear chubby because of the deposition of fat within adipose tissue during the last The neonatal period extends from birth to the end of the first trimester of pregnancy. Although growth is rapid during this the inability of the kidneys to excrete concentrated urine; large period, the most drastic changes are physiological. Immunity is not well de- newborn must immediately adapt to major environmental veloped and is limited to that obtained from the mother through changes, including thermal stress; rapid bacterial colonization of placental transfer. For this reason, newborns need to be guarded the skin, oral cavity, and GI tract; a barrage of sensory stimuli; from exposure to infectious diseases. Virtually all of the neurons of the nervous system are pre- The most critical need of the newborn is the establishment sent in a newborn, but they are immature and the newborn has of an adequate respiratory rate to ensure sufficient amounts of little coordination. The normal respiratory rate of a newborn is 30 to 40 res- by lower cerebral centers and the spinal cord. A newborn has many reflexes, some indicative of neuro- The heart of a newborn appears to be large relative to the tho- muscular maturity and others essential for life itself. Four reflexes racic cavity (compared to the heart of an adult) and has a rapid critical to survival are (1) the suckling reflex, triggered by any- rate that ranges from 120 to 160 beats per minute. Developmental © The McGraw−Hill Anatomy, Sixth Edition Development Anatomy, Postnatal Companies, 2001 Growth, and Inheritance Chapter 22 Developmental Anatomy, Postnatal Growth, and Inheritance 777 2 month 3 month Newborn 2 5 13 22 years embryo fetus FIGURE 22. The head of a newborn accounts for a quarter of the total body length, and the lower appendages account for about one-third. In an adult, the head constitutes about 13% of the total body length, whereas the lower appendages constitute approximately 50%. Babies born more than 3 weeks before the due date are gen- fontanels to close. The brain is two-thirds of its adult size at the erally considered premature, but because errors are com- end of the first year and four-fifths of its adult size at the end of monly made in calculating the delivery date, prematurity is defined by neonatal body weight rather than due date. By this definition, ap- By 2 years, most infants weigh approximately four times proximately 8% of newborns in the United States are premature. The Postmature babies are those born 2 or more weeks after the body proportions of a 2-year-old are certainly not the same as due date. They frequently weigh less than they would have if they had been born at term because the placenta often becomes less effi- those of an adult (fig. Growth is a differential process, re- cient after a full-term pregnancy. Approximately 10% of newborns in sulting in gradual changes in body proportions. Eight more teeth erupt during the second year, mak- Infancy ing a total of 14 to 16, including the first deciduous molars and The period of infancy follows the neonatal period and encom- canine teeth. Infancy is characterized by tremen- The growth rates of children vary tremendously. Body lengths dous growth, increased coordination, and mental development. A more objective evaluation of a child’s physical development is determined through radiographic analysis of months and triple it in a year. The formation of subcutaneous adi- skeletal ossification in the carpal region (fig. Growth decelerates during the second year, dur- ing which time the infant gains only about 2. During Childhood the second year, the infant develops locomotor and manipulative control and gradually becomes more lean and muscular. Childhood is the period of growth and development extending Body length increases during the first year by 25 to 30 cm from infancy to adolescence, at which time puberty begins. Head circumference increases by approximately until preadolescence, which is characterized by a growth spurt. There is an average increase in height of 6 cm ually diminishes in size after 6 months and becomes effectively (2. The circumference of the head increases closed at any time from 20 to 24 months. The first permanent teeth generally erupt during the Van De Graaff: Human VII. Developmental © The McGraw−Hill Anatomy, Sixth Edition Development Anatomy, Postnatal Companies, 2001 Growth, and Inheritance 778 Unit 7 Reproduction and Development (a) (b) (c) FIGURE 22. Lymphoid tissue is at its peak of development during mid- childhood and generally exceeds the amount of such tissue in the normal adult. Children need the extra lymphoid tissue to combat childhood diseases, especially in countries where nutrition is poor and health care is minimal. Childhood obesity can become a serious physical and psy- chological problem if not corrected. Overweight children usu- ally exercise less and run a greater risk of contracting serious illnesses. Frequently, they are teased and rejected by classmates, which causes psychological stress.

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Once the diver surfaces cheap suhagra 100mg otc erectile dysfunction treatment vancouver, the heart response in humans discount suhagra 100mg without a prescription erectile dysfunction supplements, but it is usually not accompanied by rate and cardiac output increase substantially; peripheral muscle exercise (e. It seems likely that repeated elevations in arterial trient flow and washing out accumulated waste products. Behavioral Conditioning Affects Cardiovascular Responses Fainting Can Be a Cardiovascular Cardiovascular responses can be conditioned (as can other Correlate of Emotion autonomic responses, such as those observed in Pavlov’s fa- mous experiments). Both classical and operant condition- Vasovagal syncope (fainting) is a somatic and cardiovascu- ing techniques have been used to raise and lower the blood lar response to certain emotional experiences. Humans can also be of specific areas of the cerebral cortex can lead to a sudden taught to alter their heart rate and blood pressure, using a relaxation of skeletal muscles, depression of respiration, variety of behavioral techniques, such as biofeedback. The cardiovascular events ac- Behavioral conditioning of cardiovascular responses has companying these somatic changes include profound significant clinical implications. Animal and human studies parasympathetic-induced bradycardia and withdrawal of indicate that psychological stress can raise blood pressure, resting sympathetic vasoconstrictor tone. There is a dra- increase atherogenesis, and predispose to fatal cardiac ar- matic drop in heart rate, cardiac output, and SVR. These effects are thought to result from an in- sultant decrease in mean arterial pressure results in uncon- appropriate fight-or-flight response. The Cardiovascular Correlates of Exercise Require Integration of Central and Peripheral Mechanisms Not All Cardiovascular Responses Are Equal Exercise causes activation of supramedullary neural net- Supramedullary responses can override the baroreceptor re- works that inhibit the activity of the baroreceptor reflex. For example, the fight-or-flight response causes the The inhibition of medullary regions involved in the barore- heart rate to rise above normal levels despite a simultaneous ceptor reflex is called central command. In such circumstances, the neurons results in withdrawal of parasympathetic tone to the heart connecting the hypothalamus to medullary areas inhibit the with a resulting increase in heart rate and cardiac output. Also, during exercise, input from ment for blood flow to exercising muscle. As exercise in- supramedullary regions inhibits the baroreceptor reflex, pro- tensity increases, central command adds sympathetic tone moting increased sympathetic tone and decreased parasym- that further increases heart rate and contractility. Many response patterns interact, reflecting the ex- ercising skeletal muscle terminate in the RVL where they tensive neural interconnections between all levels of the further augment sympathetic tone. CNS and interaction with various elements of the local During exercise, blood flow of the skin is largely influ- control systems. For example, the baroreceptor reflex inter- enced by temperature regulation, as described in Chapter 17. Cutaneous sympa- thetic nerves participate in body temperature regulation The Diving Response Maintains Oxygen (see Chapter 29), but also serve the baroreceptor reflex. At moderate levels of heat stress, the baroreceptor reflex can Delivery to the Heart and Brain cause cutaneous arteriolar constriction despite elevated The diving response is best observed in seals and ducks, core temperature. An experienced diver can ex- baroreceptor reflex cannot overcome the cutaneous vasodi- hibit intense slowing of the heart rate (parasympathetic) lation; as a result, arterial pressure regulation may fail. CARDIOVASCULAR SYSTEM The reflex masks some of the direct cardiac effects of NE by significantly increasing cardiac parasympathetic tone. In Various hormones play a role in the control of the cardio- contrast, epinephrine causes vasodilation in skeletal muscle vascular system. SVR may actually fall and mean arte- clude the adrenal medulla, posterior pituitary gland, kid- rial pressure does not rise. At Circulating Epinephrine Has high concentrations, epinephrine binds to 1-adrenergic receptors and causes peripheral vasoconstriction; this level Cardiovascular Effects of epinephrine is probably never reached except when it is When the sympathetic nervous system is activated, the ad- administered as a drug. This increased sensitivity to neurotransmitters is small relative to changes in NE resulting from the direct re- referred to as denervation hypersensitivity. Several factors lease from nerve endings close to vascular smooth muscle contribute to denervation hypersensitivity, including the and cardiac cells. Increased circulating epinephrine, how- absence of sympathetic nerve endings to take up circulating ever, contributes to skeletal muscle vasodilation during the norepinephrine and epinephrine actively, leaving more fight-or-flight response and exercise. In addition, nephrine binds to 2-adrenergic receptors of skeletal mus- denervation results in up-regulation of neurotransmitter re- cle arteriolar smooth muscle cells and causes relaxation. During exercise, circulating levels of the heart, circulating epinephrine binds to cardiac cell 1- norepinephrine and epinephrine increase. Because of their adrenergic receptors and reinforces the effect of NE re- enhanced response to circulating catecholamines, trans- leased from sympathetic nerve endings. A comparison of the responses to infusions of epineph- rine and norepinephrine illustrates not only the different effects of the two hormones but also the different reflex re- The Renin-Angiotensin-Aldosterone System sponse each one elicits (Fig. Epinephrine and norep- Helps Regulate Blood Pressure and Volume inephrine have similar direct effects on the heart, but NE The control of total blood volume is extremely important elicits a powerful baroreceptor reflex because it causes sys- in regulating arterial pressure. Because changes in total blood volume lead to changes in central blood volume, the long-term influence of blood volume on ventricular end-di- Epinephrine Norepinephrine astolic volume and cardiac output is paramount.

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