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Adrenal Glands The paired adrenal glands are located above each kidney (see fig cheap 80mg tadapox with mastercard impotence psychological treatment. Each adrenal is composed of two parts: an outer Parasympathetic (Craniosacral) Division adrenal cortex and an inner adrenal medulla buy 80 mg tadapox with amex erectile dysfunction pills south africa. These two parts The parasympathetic division is also known as the craniosacral di- vision of the autonomic system. This is because its preganglionic neurons originate in the brain (specifically, the midbrain, pons, adrenal: L. Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 Chapter 13 Autonomic Nervous System 441 Celiac ganglion Adrenal gland Superior mesenteric ganglion Left kidney Renal plexus First lumbar sympathetic Aortic ganglion plexus Inferior mesenteric ganglion Pelvic sympathetic chain FIGURE 13. Another group of neurons in the fa- parasympathetic ganglia, which are called terminal ganglia, supply cial nerve terminate in the submandibular ganglion, which the postganglionic neurons that synapse with the effector cells. Preganglionic neurons of the glossopharyngeal nerve the sympathetic and parasympathetic divisions. It should be synapse in the otic ganglion, which sends postganglionic neurons noted that, unlike sympathetic neurons, most parasympathetic to innervate the parotid gland. Cutaneous effectors Nuclei in the medulla oblongata contribute preganglionic (blood vessels, sweat glands, and arrector pili muscles) and blood neurons to the very long vagus nerves, which provide the most vessels in skeletal muscles thus receive sympathetic but not extensive parasympathetic innervation in the body (see parasympathetic innervation. As the paired vagus nerves pass through the thorax, Four of the twelve pairs of cranial nerves contain pregan- they contribute to the cardiac plexus and the pulmonary plexuses glionic parasympathetic neurons. Branches of the pulmonary plexuses ac- facial (VII), glossopharyngeal (IX), and vagus (X) nerves. Below the Parasympathetic neurons within the first three of these cranial pulmonary plexuses, branches of the vagus nerves merge to form nerves synapse in ganglia located in the head; neurons in the the esophageal plexuses. The vagal trunks enter the ab- parasympathetic neurons that originate in the oculomotor nuclei dominal cavity through the esophageal hiatus (opening) in the of the midbrain. Neurons from the vagal trunks innervate the stom- ciliary ganglion, whose postganglionic neurons innervate the cil- ach on the anterior and posterior sides. Branches of the vagus iary muscle and constrictor muscles in the iris of the eye. Pregan- nerves within the abdominal cavity also contribute to the celiac glionic neurons that originate in the pons travel in the facial plexus and plexuses of the abdominal aorta. Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 442 Unit 5 Integration and Coordination Oculomotor nerve Facial nerve Glossopharyngeal nerve Vagus nerve FIGURE 13. Solid lines indicate pre- ganglionic neurons and dashed lines indicate postganglionic neurons. Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 Chapter 13 Autonomic Nervous System 443 TABLE 13. Compare the origins of preganglionic sympathetic and They provide parasympathetic innervation to the heart, lungs, parasympathetic neurons and the locations of sympathetic esophagus, stomach, pancreas, liver, small intestine, and upper and parasympathetic ganglia. Using a simple line drawing, illustrate the sympathetic path- rons arise from terminal ganglia within these organs and inner- way from the spinal cord to the heart. Label the pregan- vate the smooth muscle tissue and glandular epithelium of these glionic neuron, postganglionic neuron, and the ganglion. Use a simple diagram to show the parasympathetic inner- provide parasympathetic innervation to the lower half of the large vation of the heart. Label the preganglionic and postgan- intestine, the rectum, and to the urinary and reproductive systems. Describe the distribution of the vagus nerve and discuss the the visceral organs thus consist of preganglionic neurons, whereas functional significance of this distribution. Define the terms white rami and gray rami and explain why A composite view of the sympathetic and parasympathetic blood vessels in the skin and skeletal muscles receive sym- divisions of the ANS is provided in figure 13. Describe the structure of the adrenal gland and explain its relationship to the sympathetic division of the ANS. Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 444 Unit 5 Integration and Coordination TABLE 13. The actions of the autonomic nervous system, together with the effects of hormones, help to maintain a state of dynamic con- Neurotransmitters of the Autonomic stancy in the internal environment. The sympathetic division gears the body for action through adrenergic effects; the parasympa- Nervous System thetic division conserves the body’s energy through cholinergic ef- The neurotransmitter released by most postganglionic sympa- fects. Homeostasis thus depends, in large part, on the thetic neurons is norepinephrine (noradrenaline).

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This can cause confusion when related subunits are given sequential numbers: b1 80mg tadapox mastercard best erectile dysfunction pills review, b2 cheap 80 mg tadapox otc erectile dysfunction treatment success rate, b3, etc. The convention is there- fore that subunits are numbered normally while stoichiometry is indicated by subscripts so that a pentamer of a4 and b3 subunits might have a stoichiometry of a42b33. NICOTINIC RECEPTORS All receptors in the 4-TM domain family are thought to form pentameric receptors in which five subunits (Fig. Their structure has been most extensively studied in the case of the nicotinic acetylcholine receptor (analogous to the muscle endplate receptor) from Torpedo electroplaque (Unwin 2000) where there is now a detailed knowledge of the receptor in both resting and active conformations. The muscle receptor has a subunit stoichiometry of two a subunits, providing the agonist binding sites, and three other subunits (b, g and d). In adult muscle an e subunit is present instead of the g subunit which is found in the foetal-type receptor. The five subunits are arranged like the staves of a barrel around the central channel. Binding of ACh to the a subunits initiates a conformational change in the protein which, by causing rotation of all five TM2 domains lining the pore, opens the ion channel. Diversity among neuronal nicotinic receptors is generated by having nine more different a subunits (a2±a10) and three further b subunits (b2±b4). These receptors are activated by nicotine and blocked by the antagonists hexamethonium, mecamylamine and trimetaphan, and the erythrina alkaloid dihydro-b-erythroidine. The neuronal nicotinic receptors are found in autonomic ganglia and in the brain may be either heteromeric (e. The a7 receptor is likely to be the source of the a-bungarotoxin binding sites in the brain observed in autoradiograms of 123I-a- bungarotoxin binding to brain sections (Clarke 1992) and a-bungarotoxin sensitive nicotinic receptors have been shown in a number of studies to stimulate transmitter release from nerve terminals such as dopaminergic terminals in the striatum and glutamatergic terminals in the cortex. Its main functional role may therefore be as a presynaptic receptor regulating transmitter release. It has a high affinity for nicotine and so may mediate some of the central effects of nicotine. Notice that a homomeric receptor has implications for the interpretation of functional studies since the number NEUROTRANSMITTER RECEPTORS 65 of agonist (and antagonist) binding sites on the receptor must equal the number of subunits. In the case of a7 receptors, Hill coefficients (see Appendix) of around 1. GLYCINE RECEPTORS Inhibitory glycine receptors with high affinity for the antagonist strychnine are predominantly found in the spinal cord and brainstem. Three different a subunits have been cloned (a1±a3) and a single b subunit (b1). Interestingly, the foetal-type of glycine receptor which is a homomer (the adult stoichiometry is likely to be a3b2) has Hill coefficients nearer 3. GABA RECEPTORS The GABA receptor subunits are one of the most diverse groups of ion channel receptor subunits in the brain. Six different a subunits (a1±a6), four b subunits (b1±b4), four g subunits (g1±g4), an e subunit, a p subunit, and three r subunits (r1±r3) have been found. This diversity of subunits is reflected in the complicated pharmacology of the GABA receptors. Functional GABA receptors can be formed by co-expression of any a subunit with any b subunit probably in the stoichiometry a2b3. However, these receptors, although activated by GABA and muscimol, potentiated by barbiturates and neurosteroids, and blocked by bicu- culline and picrotoxin, lack classical benzodiazepine sensitivity which can be restored to the molecule by co-expressing a g subunit with a and b. These are activated by the weak agonist CACA, relatively insensitive to bicuculline, not sensitive to barbiturates or neuro- steroids, and blocked by TPMPA. They have been described in the retina (where r1is expressed) but relatively little is known of their function in the brain although they are widely expressed (Bormann 2000). For example, all three r subunits are found in cerebellar Purkinje cells. Native GABAC receptors may be homomeric pentamers of a single r subunit or heteromeric pentamers of more than one of the r subunits. GABAC receptor dose±response curves have Hill slopes around 3 or greater, unlike GABAA receptor dose±response curves where the Hill slope is usually around 2.

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Adrenal androgens would be significantly elevated in pa- gest that the patient may be hyperthyroid cheap 80 mg tadapox with visa erectile dysfunction treatment pumps. However purchase 80mg tadapox erectile dysfunction is caused by, goiter tients with virilizing forms of congenital adrenal hyperpla- can also occur in hypothyroidism. Adrenal hyperplasia is usually due to defects in cortisol roid disease runs in families, the family history suggests production. Therefore, the serum concentrations of precur- that the thyroiditis might be due to an autoimmune re- sors of cortisol biosythesis such as progesterone, 17 -hy- sponse. The laboratory should determine the blood levels of thyroid In addition, serum ACTH would be elevated as a result of hormones (T4 and T3) and TSH. Thyroid hormones should the lack of negative feedback from the absent cortisol. Genetic defects in the gene for 11 -hydroxylase, resulting in gression of Hashimoto’s disease or decreased if the patient a reduction in the activity of this enzyme, would result in in- has Graves’ disease. The laboratory should measure antibodies to TSH receptor, ylase, which impair the activity of the enzyme, would not thyroid peroxidase, and thyroglobulin. Since 11-deoxy- peroxidase are elevated to the greatest extent in cortisol has significant mineralocorticoid activity, excess Hashimoto’s disease. Antibodies to TSH receptor, thyroid peroxidase, and thy- tension, rather than the volume depletion and hypotension roglobulin can all be elevated in Graves’ disease. Treatment would be directed toward replacement of gluco- 648 PART IX ENDOCRINE PHYSIOLOGY corticoids and mineralocorticoids. Exercise not only helps to control weight, it stimulates glu- place the missing cortisol and also suppress ACTH secre- cose uptake in skeletal muscle, lessening the requirements tion. With less ACTH stimulation of steroid production from for injected insulin. Mineralocorticoids are given to treat the “salt wasting” that CASE STUDY FOR CHAPTER 36 occurs in the absence of aldosterone. Bone Fractures CASE STUDY FOR CHAPTER 35 A 38-year-old Caucasian man recently came to the atten- tion of his physician when he suffered the second of two Type 2 Diabetes bone fractures in the past year and a half. He previously A 65-year-old semi-retired college professor was diag- was in relatively good health, was not a smoker, and used nosed with type 2 diabetes about 4 years ago during a alcohol only moderately. However, his only form of exer- routine physical examination at his family doctor’s of- cise was cutting the lawn on weekends during the sum- fice. He has not required any major surgeries tablet daily of an oral antidiabetic drug of the sulfony- during his lifetime, and had only minor bouts of the typi- lurea class and two daily injections of insulin. However, at age eight he was di- tient’s doctor also recommended modest weight loss agnosed with asthma after he suffered severe respiratory and a regular exercise program. With diligence to the problems during a baseball game on a hot summer day. For The fractures that the patient experienced were to the about one week after the surgery, the patient had to in- left wrist and the right forearm. In both cases, the trauma crease his insulin dosage to maintain normal blood glu- that caused the fracture was relatively minor. He gradually returned to his presurgery in- that there may be an underlying problem, his physician sulin dose. Results of these Because of the surgery, the patient vows to take better studies show that the patient has a considerable reduc- care of himself. He increases his physical activity and be- tion in bone mass compared with other men of the same gins a diet that results in loss of 7 kg in 3 months. What is the most probable underlying cause for the pa- Questions tient’s problem? Osteoporosis and, perhaps, glucocorticoid-induced osteo- gain the weight he lost after surgery? Because the patient is young and has a relatively healthy for type 2 diabetes? Glucocorticoids increase bone loss by inhibiting os- epinephrine and norepinephrine, both of which inhibit in- teoblasts, stimulating bone resorption, impairing intestinal sulin secretion.

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