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In A patient swallows radiopaque barium order prednisolone 5mg with mastercard, which coats the lining of the stomach and duodenum discount prednisolone 20mg visa. These structures and certain abnormalities the stomach generic 5mg prednisolone overnight delivery, which serves as a “holding organ” for ingested food purchase prednisolone 10mg overnight delivery, may then show up in the radiograph cheap 40 mg prednisolone visa. The stomach is divided into four regions: the cardia, fun- rect contact with the diaphragm. The cardia is the narrow portion, and the pylorus is the funnel-shaped terminal portion. The pyloric sphincter is the modified circular muscle at the end The fundus is the dome-shaped portion to the left of and in di- of the pylorus, where it joins the small intestine. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 650 Unit 6 Maintenance of the Body Gastric folds FIGURE 18. Greek word meaning “gatekeeper,” and this junction is just that, regulating the movement of chyme into the small intestine and Columnar prohibiting backflow. The broadly rounded surfaces are referred to as the anterior and pos- terior surfaces. The lesser omentum extends between the lesser cur- vature and the liver, and the greater omentum is attached to the Gastric glands greater curvature (see fig. The mucosa is further characterized by the presence of microscopic gastric pits and gastric glands (figs. There are five types of cells in the gastric glands that se- crete specific products. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 18 Digestive System 651 Gastric pits (a) Mucous cell Mucosa Gastric gland Parietal Submucosa cell Principal cell (b) FIGURE 18. Phase Response In addition to these products, the gastric mucosa (probably Cephalic phase Sight, taste, small or mental stimuli evoke parasympathetic response via vagus nerves; 50–150 the parietal cells) secretes intrinsic factor, a polypeptide that is re- ml of gastric juice is secreted quired for absorption of vitamin B12 in the small intestine. Con- Gastric phase Food in the stomach stretches the mucosa, and tinued gastric activity when the stomach is empty causes hunger chemical breakdown of protein stimulates the release sensations known as hunger pangs. Eating fills the stomach result- of gastrin; gastrin stimulates the production of ing in hunger satiety, or a perception of “fullness. Mucus, secreted cells to release intestinal gastrin; intestinal gastrin by mucous cells of the stomach, is important in preventing hy- stimulates the production of additional small drochloric acid and the digestive enzyme pepsin from eroding the quantities of gastric juice stomach wall. Peptic ulcers may be caused by an increase in cellular secretion or by insufficient secretions of protective mucus. Another protective feature is the rapid mitotic activity of the columnar epithe- lium of the stomach. Nevertheless, in the United States pathetic impulses promote gastric activity, the phases of which approximately 10% of the male population and 4% of the female pop- are presented in table 18. Vomiting is the reflexive response of emptying the stomach Regulation of gastric activity is autonomic. This action is thetic neurons arise from the celiac plexus, and the parasympa- controlled by the vomiting center of the medulla oblongata. Parasympathetic uli within the GI tract, especially the duodenum, may activate the neurons synapse in the myenteric plexus between the muscular vomiting center, as may nauseating odors or sights, motion sick- layers and in the submucosal plexus in the submucosa. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 652 Unit 6 Maintenance of the Body the lower esophageal sphincter and contraction of the pyloric It is called the “small” intestine because of its relatively small di- portion of the stomach; (3) a shallow inspiration and closure of ameter compared to that of the large intestine. The small intes- the glottis; and (4) compression of the stomach against the liver tine is the body’s major digestive organ and the primary site of by contraction of the diaphragm and the abdominal muscles. Its digestive enzymes, along with those of This reflexive sequence causes a forceful ejection of vomit. The the salivary glands, gastric glands, and pancreas, are summarized feeling of nausea is caused by stimuli in the vomiting center and in table 18. The branches of the plexus contain sensory fibers, The only function of the stomach that appears to be essential for life is the secretion of intrinsic factor. This polypeptide is postganglionic sympathetic fibers, and preganglionic parasympa- needed for the intestinal absorption of vitamin B12, which is required thetic fibers. The arterial blood supply to the small intestine is for maturation of red blood cells in the bone marrow. Following surgi- through the superior mesenteric artery and branches from the cal removal of the stomach (gastrectomy), a patient has to receive vi- celiac trunk and the inferior mesenteric artery. The venous tamin B12 (together with intrinsic factor) orally or through injections, so that he or she will not develop pernicious anemia. This vein unites with the splenic vein to form the hepatic portal vein, which carries nutrient-rich blood to the liver (see fig. Describe the three stages of deglutition with reference to the structures involved.

NEUROCHEMISTRY OF GLYCINE SYNTHESIS AND CATABOLISM OF GLYCINE The details of glycine metabolism within neural tissue are poorly understood best prednisolone 20mg,and it is unclear to what extent neurons depend on de novo synthesis or uptake of glycine buy prednisolone 10 mg amex. Two enzymes are important in glycine metabolism; serine hydroxymethyltransferase (SHMT) cheap prednisolone 10mg overnight delivery,which is thought to be present in the mitochondria of both neurons and glia cheap prednisolone 5mg overnight delivery,and the four-enzyme complex known as the glycine cleavage system (GCS) 20mg prednisolone for sale,present in glia. SHMT catalyses the interconversion of L-serine and glycine while GCS catalyses the breakdown of glycine. Within neurons the action of SHMT leads to the conversion of L-serine to glycine,while in glia the coupling of SHMT and GCS results in the conversion of glycine to L-serine (Verleysdonk et al. The L-serine derived from glycine may be further metabolised,or released from glial cells to be taken up into neurons,forming a cycle analogous to the glutamine±glutamate cycle shown in Fig. Glycine can also be formed by the action of aminotransferases (such as alanine- glyoxylate transaminase or glycine transaminase),in which the amino group from a donor amino acid is transferred onto glyoxlate,producing glycine and a keto acid. As described above,it seems likely that a common transport mechanism (VIAAT) is responsible for the accumulation of both amino acids. This will be determined by the expression of the respective biosynthetic enzymes and plasma membrane transporters. The extent and significance of such co-release is unclear,but its effects will obviously depend on the types of pre- and postsynaptic receptors present at the synapse. Possible benefits of co-release may stem from the different kinetic properties of GABAA and glycine receptors,the ability to activate GABAB receptors or the modulatory action of glycine at NMDA receptors. UPTAKE OF GLYCINE Glycine is removed from the extracelluar space by high-affinity uptake into neurons and glia. All are members of the Na‡- and ClÀ-dependent family transporters and are encoded by two independently regulated genes, GLYT1 and GLYT2. Three GLYT1 isoforms (1a,b and c) and two GLYT2 isoforms (2a and b) are generated by alternative splicing (reviewed by AMINO ACIDS: INHIBITORY 247 Figure 11. The receptors are shown with a pentameric assembly but the a and b subunits are distinct from those that form GABAA receptors. Picrotoxin is also an effective glycine antagonist and in recombinant systems is selective for homomeric receptors Palacin et al. The distribution of the transporters with respect to glycine receptors has led to the suggestion that both transporters are associated with glycinergic synapses,while GLYT1 may also regulate extracellular glycine levels at glutamatergic synapses and hence affect the activity of NMDA receptors. Relatively few selective blockers of glycine uptake have been described. GLYCINE RECEPTORS Glycine receptors can be activated by a range of simple amino acids including glycine, b-alanine and taurine,and are selectively blocked by the high-affinity competitive antagonist strychnine (Fig. Glycine receptors were originally isolated from spinal cord membranes on the basis of strychnine binding,and found to be composed of two membrane-spanning polypeptides (termed a and b) and an associated cytoplasmic protein (gephyrin). To date,four a subunit genes (a1±4) and a single b subunit gene have been identified,with several additional variants of the a1 and a2 isoforms produced by alternative splicing (reviewed by Kuhse,Betz and Kirsch 1995; Rajendra,Lynch and Schofield 1997). The a and b subunits are formed from approximately 420 and 470 amino acids,respectively,are similar in structure to GABAA subunits,and likewise form pentameric receptors with a central ion channel permeable to ClÀ and HCO À. In 3 recombinant expression systems the a subunits give rise to functional homomeric receptors or co-assemble to form heteromeric receptors. The b subunit is only 248 NEUROTRANSMITTERS,DRUGS AND BRAIN FUNCTION incorporated into receptors when co-expressed with a subunits. Native receptors in the adult spinal cord contain 3 a1and2b subunits whereas neonatal receptors are homomeric receptors formed from a2 subunits. The cytoplasmic protein gephyrin is not needed for the formation of functional receptors but plays an important role in the clustering of both glycine and GABAA receptors (Moss and Smart 2001). Glycine receptors in the postsynaptic membrane,like GABAA receptors,most commonly generate a hyperpolarizing IPSP. In the brainstem,glycine receptors have also been shown to be present on presynaptic terminals,where they induce a small depolarisation that activates Ca2‡ channels and increases neurotransmitter release (Turecek and Trussell 2001). This differs from the action of presynaptic GABAA receptors described above,where the depolarisation induced is sufficient to inactivate Na‡ channels and decrease neurotransmitter release. Unlike GABA receptors,glycine A receptors are inhibited by some steroids,unaffected by benzodiazepines and are relatively insensitive to barbiturates. However,native and recombinant glycine receptors are positively modulated by a wide range of general anaesthetics,including diethyl ether,halothane,isoflurane,chloral hydrate,brometone and trichloroethylene. REFERENCES Asada,H,Kawamura,Y,Maruyama,K,Kume,H,Ding,R,Ji,FY,Kanbara,N,Kuzume,H, Sanbo,M,Yagi,T and Obata,K (1996) Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.

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This buildup pulls the pharynx has both digestive and respiratory functions purchase prednisolone 40mg otc. The sup- gum away from the teeth generic prednisolone 5 mg fast delivery, allowing bacterial infections to develop discount 40 mg prednisolone amex. Saliva functions as a solvent in Wharton’s duct: from Thomas Wharton purchase 10 mg prednisolone free shipping, English physician order 10mg prednisolone fast delivery, 1614–73 cleansing the teeth and dissolving food molecules so that they Rivinus’ ducts: from August Quirinus Rivinus, German anatomist, 1652–1723 Van De Graaff: Human VI. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 646 Unit 6 Maintenance of the Body Accessory salivary gland Tongue Accessory salivary gland Lingual frenulum Parotid gland Opening of submandibular duct Sublingual ducts Parotid duct Masseter muscle Sublingual gland Submandibular Submandibular gland duct Mandible (cut) FIGURE 18. Mucous cells Intralobular parotid duct Lumen of Seromucous submandibular acini intralobular duct Serous cells (a) (b) Mucous cells Serous cells Intralobular (c) sublingual duct FIGURE 18. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 18 Digestive System 647 TABLE 18. The right side has been cut away to illustrate the interior structures in the pharynx. The middle constrictor three regions: the nasopharynx, posterior to the nasal cavity; the muscle arises from the hyoid bone and stylohyoid ligament and oropharynx, posterior to the oral cavity; and the laryngopharynx, encircles the middle portion of the pharynx. The superior constrictor mus- preventing air from entering the esophagus. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 648 Unit 6 Maintenance of the Body The motor and most of the sensory innervation to the Adventitia pharynx is via the pharyngeal plexus, situated chiefly on the middle constrictor muscle. It is formed by the pharyngeal Tunica branches of the glossopharyngeal and vagus nerves, together with muscularis a deep sympathetic branch from the superior cervical ganglion. Submucosa The pharynx is served principally by ascending pharyngeal Mucosa arteries, which branch from the external carotid arteries. The pharynx is also served by small branches from the inferior thyroid Lumen arteries, which arise from the thyrocervical trunk. Describe the location of the parotid, submandibular, and sub- The lower esophageal (gastroesophageal) sphincter is a lingual ducts and state where they empty into the oral cavity. After food or fluid pass into the stomach, this sphincter constricts to prevent the stomach con- tents from regurgitating into the esophagus. There is a normal ESOPHAGUS AND STOMACH tendency for this to occur because the thoracic pressure is lower than the abdominal pressure as a result of the air-filled lungs. A bolus of food is passed from the esophagus to the stomach, where it is churned and mixed with gastric secretions. The chyme The lower esophageal sphincter is not a well-defined sphinc- thus produced is sent past the pyloric sphincter of the stomach to ter muscle comparable to others located elsewhere along the GI tract, and it does at times permit the acidic contents of the stom- the duodenum. This can create a burning sensation commonly called heartburn, although the heart is not involved. Certain Objective 10 Describe the location, gross structure, and mammals, such as rodents, have a true lower esophageal sphincter functions of the stomach. Objective 11 Describe the histological structure of the esophagus and stomach. List the cell types in the gastric mucosa, along with their secretory products. For descriptive purposes, deglutition The esophagus is that portion of the GI tract that connects the is divided into three stages. It is a collapsi- The first deglutitory stage is voluntary and follows mastica- ble tubular organ, approximately 25 cm (10 in. During this stage, the mouth is closed at the larynx and lying posterior to the trachea. A bolus is formed as The esophagus is located within the mediastinum of the the tongue is elevated against the transverse palatine folds thorax and passes through the diaphragm just above the opening (palatal rugae) of the hard palate (see fig. The upper third of the esophagus con- and are elicited by stimulation of sensory receptors located at the tains skeletal muscle; the middle third, a combination of skeletal opening of the oropharynx. Pressure of the tongue against the and smooth muscle; and the terminal portion, smooth muscle only. The soft palate and pendulant palatine uvula are elevated to esophagus: Gk. Digestive System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 18 Digestive System 649 Esophagus Esophagus Fundus Cardia Peristaltic contraction of muscularis layer of esophagus Lesser Greater curvature curvature Swallowed bolus entering stomach Duodenum Pylorus Body Stomach (a) FIGURE 18. Elevation of the larynx against the epiglottis seals the glottis so that food or fluid is less likely to enter the trachea.

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In (a) proven 10 mg prednisolone, the topology of the 4- TM domain subunits is illustrated embedded in the cell membrane order 40 mg prednisolone free shipping. Receptors in this class are the nicotinic acetylcholine receptors 5 mg prednisolone fast delivery, GABAA and GABAC receptors buy prednisolone 10 mg amex, glycine receptors and 5-HT3 receptors purchase prednisolone 40mg visa. Shown below is the likely pentameric stoichiometry of the 4-TM domain receptors with TM2 of each subunit lining the central ion channel. In (b), the transmembrane topology of the ionotropic glutamate receptors is shown. TM2 creates a pore-forming loop which penetrates into the cell membrane from the intracellular side. As illustrated below, the likely stoichiometry of the glutamate receptors is a tetramer. The exact contribution of TM1, TM3 or TM4 to forming the ion channel is uncertain. These subunits cross the cell membrane only twice and the ion channel is probably formed by a short polypeptide loop entering the membrane from the outside. The exact stoichiometry of the P2X receptors is uncertain but current evidence supports the suggestion that they are trimers agonist binding site is located in the amino terminal domain before the start of TM1 and the ion channel is formed by the TM2 domains of each subunit which come together to make up the complete receptor. Thus the amino acids in TM2 determine the ion conductance properties of the channel. For GABA and glycine receptors a Cl7 channel is formed while for the other ion channel receptors, the channel is largely cation non-selective for monovalent ions such as Na‡ and K‡ and is often also permeable to calcium. One of the key differences between different ion channel receptors for glutamate, ACh, 5-HT and ATP is in their relative permeability to calcium and this is controlled by the amino acids which line the ion channel. The ionotropic glutamate receptors (kainate, AMPA and NMDA) are formed by subunits which are predicted to cross the cell membrane three times (Fig. The ionotropic glutamate receptor subunits have a large extracellular amino terminal domain and a long intracellular carboxy terminal domain (Fig. The P2X receptor subunits are unusual in having only two transmembrane domains with both the amino terminal and carboxy terminal located intracellularly. The ion channel is proposed by analogy with the structure of some potassium channels to be formed by a short loop which enters the membrane from the extracellular side (North and Surprenant 2000). Subunit stoichiometry The ion channel receptors are multi-subunit proteins which may be either homomeric (made up of multiple copies of a single type of subunit) or heteromeric (composed of more than one subunit type). These subunits come together after synthesis in the endoplasmic reticulum to form the mature receptor. A receptor composed of two a and three b subunits is therefore denoted as having a stoichiometry of a2b3. This can cause confusion when related subunits are given sequential numbers: b1, b2, 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.

Facial Taste buy cheap prednisolone 10mg on line, sensation of external ear order prednisolone 10 mg without a prescription, control of salivary glands cheap prednisolone 5 mg without prescription, tears purchase 5 mg prednisolone amex, muscles in facial expression VIII generic prednisolone 20mg free shipping. Glossopharyngeal Swallowing, sensation of pain, taste, touch from tongue and throat X. Vagus Heartbeat, digestion, speech, swallowing, respiratory function, gland functions XI. Accessory Movement of head and shoulders, muscles of pharynx and larynx in throat, production of voice sounds XII. Spinal nerves and body, the autonomic nervous system their related functions are illustrated in stimulates immediate, involuntary re- Table 3–2. For example, in response to a Nerves control both voluntary and in- speck of dust in the eye, tears are pro- voluntary functions in the body. In response to a fearful situation, that control voluntary functions (such as the heart beats faster. Nerves that are concerned with the control of invol- Table 3–2 Spinal Nerves and untary functions are part of a subcatego- Related Functions ry of the peripheral nervous system called the autonomic nervous system. Spinal Nerve Area of Function The autonomic nervous system inte- grates the work of vital organs, such as the Cervical (C1-C8) Back of head, neck, heart and lungs. Its primary function is to shoulders, arms, hands, coordinate the activity of internal organs diaphragm so that they can make adaptive respons- Thoracic (T1-T12) Chest, back, regions of es to changing external situations in abdomen order to maintain internal equilibrium. Lumbar (L1-L5) Lower back, parts of Nerve fibers monitor the activities of thighs and legs internal organs as well as changes in the Sacral (S1-S5) Regions of thighs, external environment. When changes are buttocks, legs, bowel, necessary to maintain internal homeosta- bladder, genital function sis (equilibrium), or to protect the 76 CHAPTER 3 CONDITIONS OF THE NERVOUS SYSTEM: PART II The autonomic nervous system is divid- rupted. Consequently, some damage to ed into two subsystems: motor, sensory, or reflex function below the injury occurs. The sympathetic nervous system ness, complete paralysis, or exaggerated, 2. The parasympathetic nervous system absent, or diminished reflexes below the These two systems work together and in level of the injury. The extent of function- opposition to control internal organs and al impairment or loss depends on the part regulate their function. Hormones and of the spinal cord injured and whether emotions can affect both systems. For instance, in some cases, swelling, comes active during stress and emergen- bleeding, or a tumor may compress the cies. In these ening respirations, making the heart beat instances, removal of the source of com- faster, dilating the pupils, stimulating pro- pression can, at times, restore function. It activates mechanisms that focus ered (complete spinal cord injury), there is on body conservation, such as decreasing no nerve function below the level of the the heart rate and constricting the pupils injury and hence no voluntary motor or of the eye. If sev- system is also an important component of erance is not complete (incomplete spinal sexual arousal in both males and females. In these instances, one portion of SPINAL CORD the spinal cord may be nonfunctional while another portion maintains some Spinal Cord Injuries function; or certain nerve tracts may still Spinal cord dysfunction can result from be functioning, but in an abnormal way. Most often, it is due The term paraparesis refers to partial to injuries from motor vehicle accidents, paralysis and indicates that some function sports injuries, falls, or violence such as remains below the level of the injury. Other causes of spinal Sometimes even when the spinal cord is cord dysfunction are compression of the not completely severed, all motor and cord from conditions such as herniated sensory function below the level of the disc, spinal tumors, infectious disorders injury may be lost if the remaining nerves such as polio or tetanus, degenerative dis- are destroyed from lack of blood supply, orders such as multiple sclerosis, or con- degeneration, or compression. When the spinal Manifestations of Spinal Cord Injury cord is injured, transmission of impulses between the brain and other parts of the Symptoms of spinal cord injury specif- body below the level of injury are inter- ically reflect the level of the injury and Conditions Affecting the Spinal Cord 77 C1 C2 C3 C4 Cervical Nerves C6 C7 C8 T1 T2 T3 T4 T5 T6 Thoracic T7 T8 Nerves T9 T10 T11 T12 L1 L2 L3 Lumbar Nerves L4 L5 S1 S2 Sacral S3 S4 Nerves S5 C1 Coccygeal Nerve Figure 3–1 Spinal Nerves. If spinal nerves are unable to tracts are injured, as with complete sever- transmit messages between the central ance of the spinal cord, both motor loss nervous system and the peripheral nerv- and sensory loss occur below that level. The degree of regardless of the level of injury, with the functional loss is dependent on the degree exception of injury at the sacral level (S-2 to which the spinal cord is injured. For through S-4), in which ambulation may example, if the afferent nerve roots in the return to normal. Individuals with spinal ascending tracts (sensory tracts) are injured, cord injuries above T-12 usually require a some sensory loss below the level of in- wheelchair for ambulation. If efferent nerve roots in the els of injury, ambulation for short dis- descending (motor tracts) are injured, some tances may be possible with braces or motor loss below the level of injury is crutches. Most individuals with of bladder and bowel function after spinal spinal cord injuries at C-4 or above must cord injury.

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