The zymogen granules contain and H2O in a reaction catalyzed by carbonic anhydrase purchase maxalt 10 mg with visa. The Also present in the stomach are various neuroendocrine CO2 is provided by metabolic sources inside the cell and cells order maxalt 10mg on line, such as G cells maxalt 10mg, located predominantly in the antrum purchase maxalt 10mg on line. These cells produce the hormone gastrin order 10 mg maxalt fast delivery, which stimulates For the H /K -ATPase to work, an adequate supply of acid secretion by the stomach. Although the mecha- trin secretion, a condition known as Zollinger-Ellison syn- nism is still unclear, there is an increase in K conductance drome, results in gastric hypersecretion and peptic ulceration. The H /K -ATPase recycles K ions back into the cell in exchange for H ions. This raises a question: How does the men through Cl channels, down an electrochemical gra- gastric mucosa protect itself from acidity? This is balanced by an equal amount of HCO3 3 layer covering the surface of the gastric mucosa. The blood coming from the ate trapped in the mucus gel layer neutralizes acid, pre- stomach during active acid secretion contains much venting damage to the mucosal cell surface. The os- motic gradient created by the HCl concentration in the gland lumen drives water passively into the lumen, thereby, Hydrochloric Acid Is Secreted by the Parietal Cells maintaining the iso-osmolality of the gastric secretion. The HCl present in the gastric lumen is secreted by the parietal cells of the corpus and fundus. The mechanism of Gastric Juice Contains Various Electrolytes HCl production is depicted in Figure 27. At a low se- etal cell actively pumps H out of the cell in exchange for cretion rate, gastric juice contains high concentrations of Na and Cl and low concentrations of K and H. When the rate of secretion increases, the concentration of Na Plasma Parietal cell Lumen decreases while that of H increases significantly. Also coupled with this increase in gastric secretion is an increase in Cl concentration. To understand the changes in elec- CO2 CO2 + H2O trolyte composition of gastric juice at different secretion Carbonic anhydrase + rates, it is important to remember that gastric juice is de- H H+ rived from the secretions of two major sources: parietal H2CO3 - ATP cells and nonparietal cells. Secretion from nonparietal cells HCO3 HCO - is probably constant; therefore, it is parietal secretion (HCl 3 ADP+Pi K+ secretion) that contributes mainly to the changes in elec- + + trolyte composition with higher secretion rates. Cl- - K K Cl - Cl- Cl Na+ Gastric Secretion Performs Digestive, Na+ ATP Protective, and Other Functions ADP+Pi + + Gastric juice contains several proteins: pepsinogens, K K pepsins, salivary amylase, gastric lipase, and intrinsic factor. The chief cells of the oxyntic glands release inactive The mechanism of HCl secretion by the pepsinogen. Pepsin also cat- CHAPTER 27 Gastrointestinal Secretion, Digestion, and Absorption 487 160 Cl- Vagal Gastric juice stimulation 140 H+ 120 ACh 2+ K+ 100 Ca Gastric hydrogen ion pump H+ 80 Gastrin cAMP Adenylyl 60 cyclase ATP 40 Histamine FIGURE 27. Chicago: Year 2 ceptors results in an increase in intracellular Ca concen- Book, 1977. The in- 2 creased intracellular Ca and cAMP interact in numerous alyzes its own formation from pepsinogen. Pepsin, an en- ways to stimulate the gastric H /K -ATPase, which brings dopeptidase, cleaves protein molecules from the inside, re- about an increase in acid secretion (see Fig. The optimal 2 how the increase in intracellular Ca and cAMP greatly pH for pepsin activity is 1. The acidity of gastric juice poses a barrier to invasion of the GI tract by microbes and parasites. The intrinsic factor, produced by stomach parietal cells, is necessary for absorp- Acid Secretion Is Increased During a Meal tion of vitamin B12 in the terminal ileum. The stimulation of acid secretion resulting from the ingestion of food can be divided into three phases: the cephalic phase, Gastric Secretion Is Under Neural and the gastric phase, and the intestinal phase (Table 27. Smelling, Hormonal Control chewing, and swallowing food (or merely the thought of Gastric acid secretion is mediated through neural and hor- food) send impulses via the vagus nerves to the parietal and G monal pathways. The nerve endings release ACh, which fector; histamine and gastrin are the hormonal effectors directly stimulates acid secretion from parietal cells. Parietal cells possess special histamine recep- nerves also release gastrin-releasing peptide (GRP), which tors, H2 receptors, whose stimulation results in increased stimulates G cells to release gastrin, indirectly stimulating acid secretion. The fact that the effect of GRP is known as enterochromaffin-like (ECL) cells are believed to atropine-resistant indicates that it works through a non- be the source of this histamine, but the mechanisms that cholinergic pathway.

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History of Anatomy © The McGraw−Hill Anatomy generic maxalt 10 mg mastercard, Sixth Edition Companies trusted 10 mg maxalt, 2001 Chapter 1 History of Anatomy 21 Review Activities Objective Questions 9 effective 10 mg maxalt. Anatomy is derived from a Greek word be the seat of intelligence was study have arisen since the introduction meaning (a) the liver generic maxalt 10 mg overnight delivery. X rays were discovered during the late Vesalius on the science of anatomy buy 10 mg maxalt with visa. Give some examples of how culture and William Harvey was his research on (a) Roentgen. List some techniques currently used to (b) the microscopic structure of study anatomy and identify the specialties spermatozoa. Define the terms anatomize, trepanation, (d) the striped appearance of skeletal paleopathology, vivisection, and cadaver. Why were the techniques of embalming a understanding during the Middle Ages. Homeostasis is a physiological term that (c) Hippocrates, Aristotle, Galen, its uses today? It refers to the (d) Aristotle, Hippocrates, Galen, which to derive anatomical terms? What ability of an organism to maintain the Harvey, Vesalius is the current trend regarding the use of stability of its internal environment by 4. Anatomy was first widely accepted as a proper names (eponyms) in referring to adjusting its physiological processes. Why do you suppose the Hippocratic oath theory of body organization and the (b) Egypt. The establishment of sound principles of of the oath are difficult to conform to in 3. You learned in this chapter that Galen medical practice earned this man the title today’s society? What is meant by the humoral theory of human in an attempt to understand (a) Hippocrates (c) Erasistratus body organization? Discuss the value and (b) Aristotle (d) Galen anatomists were influenced by this limitations of using mammalian 6. Which of the four body humors was specimens (other than human) in the theory? When did it cease to be an believed by Hippocrates to be associated laboratory portion of a human anatomy influence on anatomical investigation and with the lungs? The anatomical masterpiece De Humani What circumstances permitted the Universities during the Early Renaissance Corporis Fabrica was the work of philosophies of Galen to survive for such were required to take a course in human (a) Leonardo. Briefly discuss the establishment of practice during those times, explain why 8. What event of about 1450 helped to anatomy as a science during the it was important for a lawyer to usher in the Renaissance? Just as geography describes the microscope his time but was severely criticized by topography for history, anatomy describes (b) an acceptance of the scientific later anatomists. What part in anatomy have resulted in advances in (d) the development of movable type did it play in the advancement of medicine. Body Organization and © The McGraw−Hill Anatomy, Sixth Edition Organization, and the Anatomical Nomenclature Companies, 2001 Human Organism Body Organization and Anatomical Nomenclature 2 Classification and Characteristics of Humans 23 Body Organization 28 Anatomical Nomenclature 30 Planes of Reference and Descriptive Terminology 33 Body Regions 35 Body Cavities and Membranes 41 Clinical Case Study Answer 45 Chapter Summary 46 Review Activities 46 Clinical Case Study A young woman was hit by a car while crossing a street. Upon arrival at the scene, paramedics found the patient to be a bit dazed but reasonably lucid, complaining of pain in her abdomen and the left side of her chest. Initial eval- uation in the emergency room revealed a very tender abdomen and left chest. The chest radio- graph demonstrated a collapsed left lung resulting from air in the pleural space (pneumothorax). The emergency room physician inserted a drainage tube into the left chest (into the pleural space) to treat the pneumothorax. Because of the finding of tenderness, a peritoneal lavage was performed.

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The media incessantly bom- bards us with professionally prepared “sound bites” and “happy talk proven maxalt 10 mg. The physician’s office environment is character- ized by continuous interruptions (e 10mg maxalt for sale. Try to minimize office dis- tractions that interrupt your attention when conversing with a patient cheap 10mg maxalt mastercard. Instead of listening to what the patient says buy maxalt 10 mg free shipping, one can easily become distracted by the patient’s manner- isms or physical characteristics order 10mg maxalt with mastercard. Medical training and patient care is oriented toward objective observations and quantitative data. Doctors often fail to take into account the equally important emotional overtones and behavior of the patient as reflected in their comments and conversation. If you become enamored by a person’s speaking style or manner of presentation, you are likely to suspend judgment about what the speaker is actually saying. Certain words or phrases can trigger negative emotional reactions in the listener. For example, if you exert extraordinary effort on a patient’s behalf and are then told, “You were just too busy for me,” you are likely to feel antagonistic toward that person. Although note-taking is essential to documenting a patient’s history, it can distract your concentration or continuity of thought and increase the patient’s anxiety. It is best to listen and make eye contact with the patient until a clear message is detected. It is best to jot down only important key words or phrases that help you recon- struct the conversation later. Most people speak at approx 125 words per minute but are capable of assimilating approx 500 spoken words per minute. The extra time is often used to think about something other than what the speaker is saying. Communica- tion is more effective if you focus only on what is being said. Listening Skills Patients often base their assessment of a physician’s competence more on communication skills than clinical talent. Some doctors have the ability to make each patient feel that whatever the patient is saying is the most important thing he or she has heard all day. Other physicians who may be just as qualified may appear impatient or uninterested. Experts on effective communication agree on the following simple rules for avoiding misinterpretation. This technique informs the speaker whether or not his or her message is being heard and understood. This is accom- plished by asking questions, making statements, or offering visual cues that indicate your understanding and degree of concurrence. By remaining silent when a patient is speaking, you are less likely to be preparing or rehearsing your response while listening. For example, a too-relaxed posture can reflect disinter- est, whereas arms crossed in front of your body often signals defensive- ness. Some doctors avoid sitting behind a desk to remove a semblance of a barrier. If you lean forward slightly and look at the patient while he or she speaks, your nonverbal communication says, “I’m interested in what you have to say. SPEAKING: VERBAL AND NONVERBAL EXPRESSION After listening to the patient, you need to respond. Tempo of Speech and Tone of Voice Some physicians have a tendency to speak rapidly or to economize on words. Often, the stress that physicians experience in their daily practice is reflected unconsciously in their tone of voice. For example, the phrase, “You should have called me,” can be said in an empathic, solicitous manner or in an impatient, accusatory way. The effect that these two styles have on a patient can differ dramatically. Pause for Assimilation and Feedback When your message is complex, pause frequently, even if you do not sense confusion in the listener.

SCHIZOPHRENIA 363 THE EXTRAPYRAMIDAL SIDE-EFFECTS (EPSs) OF NEUROLEPTIC DRUGS These take three basic forms (1) Acute dyskinesias (2) Parkinsonian-like symptoms purchase maxalt 10 mg line, e maxalt 10 mg discount. It is not surprising that a DA antagonist (especially those acting primarily on D2 receptors) should produce the symptoms of Parkinsonism buy maxalt 10mg overnight delivery, a disorder caused by inadequate DA function (see Chapter 15) discount maxalt 10mg online, nor that its intensity or rate of onset over some weeks or months should increase with D2 antagonistic potency safe 10mg maxalt. Tolerance to this adverse effect can develop without affecting antipsychotic activity but the speed with which Parkinsonism resolves after stopping therapy may be from 3 to 12months and can persist indefinitely in some cases. The late (tardive) dyskinesias, which mainly involve facial muscles, can take months or years to develop. They occur in 20±40% of patients, may not cease after stopping the drug and in fact can get worse, or even start then. Since they can be reduced temporarily by increasing neuroleptic dose it would appear that they do really result from DA overactivity and that the antagonism is not adequate. Certainly many experimental studies show that long-term neuroleptic dosing causes a compensatory increase in DA receptor number which would predispose to dyskinesias. Against this view are the findings that the increase in receptor number may precede dyskinesias by many weeks, receptor number but not dyskinesias routinely decline after drug withdrawal and while all patients should develop increased receptor number only some show dyskinesias. The dyskinesias are also more common in schizophrenics with clear negative symptoms and most brain damage and, since they have been seen in some untreated schizophrenics, could be a latent feature brought out by neuroleptics. Of course if the A9 neurons have been depolarised by the neuroleptics (see above) it is difficult to see how they can become so active unless the depolarisation also wears off. ATYPICAL NEUROLEPTICS Typical neuroleptics reduce the positive symptoms of schizophrenia at the expense of producing EPSs but the so-called atypical neuroleptics have less tendency to cause EPSs. Clozapine can even be effective in patients refractory to other neuroleptics. It is clearly a special drug, so special in fact that although it was once withdrawn because it causes agranulocytosis in some patients (2%), it has been reintroduced, alongside careful blood monitoring, for refractory cases. This has been shown by (1) increased DA turnover through DOPAC and HVA production in vitro, (2) augmented DA and DOPAC release by microdialysis in vivo and (3) increased c-fos-like expression. How the atypical neuroleptics achieve this differential effect is less clear but they could achieve some control of schizophrenia without producing EPSs by: (1) Acting primarily on a particular subset of DA receptors (2) Antagonising (or augmenting) some other NT(s) instead of, or in addition to, DA (3) Having a particular but appropriate profile of DA and other NT (antagonistic) effects These possibilities will be considered in turn. Significance of different DA receptors So far we have generally just alluded to the neuroleptics as DA receptor antagonists. Clearly, if the DA released at the terminals of one dopaminergic tract acted on a subset of DA receptors that were different from those found postsynaptically at other tracts then some specificity of antagonist action might be achieved. Unfortunately there is no evidence that different pathways innervate different DA receptor populations and as with the use of agonists in PD, the D2 receptor is dominant. Specific D1 antagonists have no anti- schizophrenic effect and antischizophrenic efficacy increases with neuroleptic affinity (potency) at D2 receptors Ð as unfortunately does the tendency to produce EPSs. Thus there is no great advantage in producing more potent D2 antagonists, other than that less drug needs to be incorporated into long-term release depot preparations. PET studies show that at effective therapeutic plasma concentrations most neuro- leptics occupy some 80% of brain D2 receptors (in the striatum at least) and this is therefore considered to be a requirement for efficacy (Pilowsky, Costa and Eli 1992; Farde 1996). If that is so then clozapine, which occupies only 20±40% of the D2 receptors at a therapeutic concentration, must have some other action which accounts for its therapeutic effectiveness. Its activity at D1 receptors has been put forward as a possibility and although it has a relatively higher affinity for D1 than D2 receptors, compared with typical neuroleptics, it is still a weak antagonist at both and in the absence of evidence for D1 (or D5) receptor involvement in schizophrenia the significance of any D1 antagonism is unclear. K1 (nM) values for clozapine at D2 and D1 receptors are 56 and 141 compared with 0. A relatively strong block of D1 compared with D2 receptors may not be the answer for schizophrenia but it could reduce the tendency to produce dyskinesias, if this depends on D1 receptor activation (see Fig. Among the D2 family of receptors (D2,D3 and D4) the D2 receptor itself seems to be the most important. At a therapeutic concentration, most neuroleptics, except clozapine (and risperidone), should, according to in vitro binding studies, be occupying 50±70% of brain D2 receptors. The picture is similar for D3 receptors but only clozapine (and SCHIZOPHRENIA 365 risperidone and olanzapine) occupy more than 50% of D4 receptors at a therapeutic dose. This relative selectivity of clozapine for D4 receptors with their restricted location, even if it is in small numbers, to the prefrontal cortex has stimulated much interest in their involvement in schizophrenia and the control of negative symptoms.

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