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Exercise: Regulation of the oxygen content furosemide 100mg on line, but not the (B) The respiratory pump and integration of multiple systems buy furosemide 100 mg otc. PO2 cheap furosemide 100 mg fast delivery, of arterial blood (C) Increased excretion of salt and New York: Oxford University Press furosemide 100 mg amex, 7. CASE STUDIES FOR PART IV • • • Answers to Case Study Questions for Chapter 11 CASE STUDY FOR CHAPTER 11 1. The disease, chronic granulomatous disease of child- Chronic Granulomatous Disease of Childhood hood, results from a congenital lack of the superoxide- An 18-month-old boy, with a high fever and cough and forming enzyme NADPH oxidase in this patient’s neu- with a history of frequent infections, was brought to the trophils. The lack of this enzyme results in deficient emergency department by his father. A blood examina- hydrogen peroxide generation by these cells when they tion shows elevated numbers of neutrophils, but no ingest or phagocytose bacteria, resulting in a compro- other defects. Normal neutrophil stem cells grown in culture may be in- produce hydrogen peroxide. The ability of this patient’s fused to supplement the patient’s own defective neu- neutrophils to generate hydrogen peroxide is found to trophils. In addition, researchers are now trying to geneti- be completely absent. What cellular defect may have led to the complete absence Reference of hydrogen peroxide generation in this patient’s neu- Baehner RL. CHAPTER 18 Control Mechanisms in Circulatory Function 305 Questions CASE STUDY FOR CHAPTER 12 1. While in the emergency department, the patient’s symptoms tigue, shortness of breath, and progressive ankle edema. What immediate action could be taken to stabilize These signs and symptoms had been worsening slowly or treat the patient? His medical history included a motor vehi- Answers to Case Study Questions for Chapter 13 cle accident 4 months ago, during which he sustained a 1. During atrial fibrillation, the AV node is incessantly stimu- deep puncture wound to the right thigh. Depending upon the conduction velocity and refrac- closed with skin sutures on the day of the accident and tory period of the node, the ventricular rate may be from 100 had healed, although the area around the injury re- to more than 200 beats/min. This leads to hypotension and appears ill and has shortness of breath at rest. Bilateral associated symptoms such as light-headedness and short- lung crackles are present. Drugs that can slow down conduction through the AV node but the amplitude of the right femoral pulse is increased. These included digi- A continuous bruit is present over the scar from his pre- talis, beta blockers, and calcium entry blockers. The superficial veins in the right AV nodal conduction, these drugs reduce the rate of excita- thigh are prominent and appear distended. At a slower ventricular rate, there is Questions more time for filling, and the output of the heart is increased. In this procedure, a strong electrical current is passed edema, lung crackles, and an elevated heart rate? Answers to Case Study Questions for Chapter 12 As repolarization occurs, a normal, coordinated rhythm is 1. The patient has an arteriovenous (A-V) fistula caused by his reestablished. During the injury, both the artery Reference and the adjacent vein in the thigh were severed; the vessels Shen W-K, Holmes DR Jr, Packer DL. In: healed but, during the healing process, a direct connection Giuliani ER, Nishimura RA, Holmes DR Jr, eds. Louis: CV Mosby, ity of flow from the artery to the vein is very high; it pro- 1996;727–747. A large A-V fistula, such as this one, allows a substantial CASE STUDY FOR CHAPTER 14 amount of the cardiac output to be shunted directly from the arterial system to the venous system, without passing Left Ventricular Hypertrophy (Aortic Stenosis) through the resistance vessels.

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The presence of an enhancing rim on post-gadolinium images has a high sensitivity and specificity for the diagnosis of soft-tissue abscess order 40 mg furosemide fast delivery. Osteomyelitis a Osteomyelitis is defined as an infection of the bone mar- row 100mg furosemide sale. The incidence of Haemophilus influenzae osteomyelitis has decreased dramatically since the intro- duction of HIB vaccination purchase 40 mg furosemide with visa. In infants cheap furosemide 40mg line, dia- physeal vessels penetrate the growth plate to reach the c epiphysis, facilitating epiphyseal and joint infections in this age group. In older children, the growth plate constitutes a barri- A 13-year-old girl presented er for the diaphyseal vessels. Vessels at the metaphysis with complaints of periods of terminate in slow-flow venous sinusoidal lakes, predis- low-grade fever and a progres- d posing the metaphysis as the starting point for acute sive swelling of the proximal hematogenous osteomyelitis. A metaphyseal defect is present, as shown with ultra- The increased pressure within the medullary cavity sonography (a) and radiography (b). Conventional radiography is usually the initial modality demonstrating deep soft-tissue swelling in early disease. Bone destruction and periosteal reaction become obvious only 7-10 days after the onset of disease. Nonetheless, con- ventional radiography is a screening method that may sug- gest the diagnosis, exclude other pathology, and can be correlated with other imaging findings. Recently, several reports have recommend the use of US for the early diagnosis of osteomyelitis, especially in Fig. A 9-year-old girl changes comprises deep edema, thickening of the perios- with a 7-month history of teum, intra-articular fluid collection, and subperiosteal ab- arthralgia presented with a 3- scess formation (elevation of the periosteum by more than week history of a swelling at the sternoclavicular joint on 2 mm). The de- Although the cortex (vertical tection of subperiosteal abscesses is especially important arrows) appears to be intact, there are echoes from the because in these patients ultrasonographically guided as- b medulla (curved arrows), piration or surgical drainage has to be considered, where- suggesting subtle permeative as patient with osteomyelitis without abscesses can be changes of the cortex facilitating the passage of sound waves into treated with antibiotics only. The proximal left clavicle (arrows) shows increased signal intensity of medulla, cortex and surrounding soft tissues. Note nor- band of decreased echogenicity bordered by a line of in- mal right clavicle. A diagnosis of cat-scratch osteitis was made by creased echogenicity representing subperiosteal fluid and the detection of Bartonella henselae DNA by PCR analysis of bone periosteal reaction, respectively [24, 25]. Robben periosteal abscesses are spindle-shaped fluid collections along the cortex of a bone, either with increased or de- creased echogenicity. Pus collections with increased or decreased echogenicity will present as avascular pe- riosteal masses with peripheral hyperemia. However, it should be noted that color Doppler flow is not detectable earlier than 4 days after the onset of symptoms. CT demonstrates osseous abnormalities earlier then con- ventional radiographs, but at the expense of a higher radia- tion dose. It is superior to MR imaging for visualizing bony destruction, gas in the bone, and a bony sequestration. Like CT, MRI is not a screening method but is invalu- a b able in demonstrating the intra- and extraosseous exten- sion of osteomyelitis. Predictors of early osteomyelitis are ill-defined, low T1 and high T2 signal intensity; poor- Fig. A 9-year-old boy with ly defined soft-tissue planes; lack of cortical thickening; fever and pain of the right thigh, 6 month after surgery for an ade- and poor interface between normal and abnormal mar- nocarcinoma of the left kidney. In chronic osteomyelitis, there is a good differentia- Ultrasonography shows reflec- tion between diseased marrow and soft-tissue abnormal- tions in quadriceps muscle with ities. Sensitivity and specificity of gadolinium-en- bright acoustic shadowing (ar- hanced MR imaging for osteomyelitis is reported at 97 rows), suspect for intramuscular gas. Blood cultures revealed c Pyomyositis gram-negative bacteria Pyomyositis is a suppurative bacterial infection in striat- ed muscle. It is rare because striated muscle is relatively resistant to bacterial infection and is encountered most The detection of an abscess in myositis is important frequently in tropical regions. All striated muscles of the because it requires drainage for complete resolution skeleton can be involved, but there is a predilection for whereas stage 1 disease can be treated with antibiotic muscles in the thigh and pelvis. US has the advantage over other modali- are trauma, diabetes mellitus, chronic steroid use, con- ties that it can be used to guide percutaneous aspiration nective tissue disorders, and immunosuppression (HIV, and drainage.

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Overall generic furosemide 100 mg visa, it remains to be seen whether or not changes in the release of 5-HT in the terminal field parallel changes in the firing rate of neurons in the Raphe nuclei discount furosemide 40 mg on line. However order furosemide 40 mg line, this question might be resolved by the recent discovery of a subpopulation of 5-HT neurons in the Raphe nuclei that is affected by aversive stimuli furosemide 100 mg cheap. It is proposed that these (presumed) 5-HT neurons form a distinct mesocorticolimbic group that, unlike neurons in other zones of the DRN and MRN, contribute to the stress response in vivo (Lowry et al. If so, this could explain the neuronal origin of the increase in 5-HT efflux in forebrain areas during stress and could suggest that certain 5-HT neurons have an important role in the stress response rather than merely governing motor activity. THE ROLE OF 5-HT IN GOVERNING FOOD INTAKE Obviously, regulation of food intake depends on many neurotransmitters and hormones but this final section will outline the role played by central 5-HT transmission in this process. It had been the belief for some time that increased 5-HT transmission in the brain reduces food intake (Blundell 1977) and this certainly explains the satiety in rats that follows infusion of 5-HT into the paraventricular nucleus (PVN) of the hypothalamus. However, recent studies using microdialysis have found that 5-HT efflux in the lateral hypothalamus is itself increased by food intake, suggesting the existence of a feedback control system. In fact, because the increase in 5-HT efflux is greater in genetically obese rats than in their lean counterparts, it has been proposed that there is a deficiency in the 5-HT inhibition of food intake in obesity. The increase in food intake induced by 5-HT1A receptor agonists is entirely consistent with the view that increased 5-HT transmission in the brain reduces food intake (hypophagia) since the activation of 5-HT1A autoreceptors in the Raphe nuclei would ensure a reduction in 5-HT release from the nerve terminals. Of course, this explanation does not tackle the question of what role, if any, is served by postsynaptic 5-HT1A receptors and, in fact, recent studies suggest that links between 5-HT1A receptor activation and food intake are far more complex than originally proposed. For instance, in microdialysis studies of the lateral hypothalamus, 5-HT efflux was reduced, as expected, by systemic administration of the 5-HT1A agonist, 8-OH-DPAT, in freely feeding, but not food-deprived, rats. The finding that 8-OH-DPAT reduces food intake in fasted pigs but increases it in satiated animals is even more difficult to explain. Clearly, more research is needed before these apparently incongruous findings can be reconciled. So far, the role(s) of other 5-HT receptors in feeding seem to be more consistent and it is generally agreed that activation of 5-HT1B or 5-HT2A/2C receptors reduces food intake. It has even been reported that stress-induced hypophagia is ameliorated by 5-HT2A antagonists and that this indicates a link between abnormal 5-HT2A-receptor mediated transmission in the PVN and anorexia nervosa (see Samanin and Grignaschi 1996). Both these compounds have actions that should lead to increased synaptic concentrations of 5-HT in the brain, albeit through different mechanisms (see below), but whether or not this actually explains the anorectic actions of d-fenfluramine is controversial. Moreover, microdialysis studies have shown that systemic administration of this drug causes a rapid but short-lived increase in the extracellular concentration of 5-HT in this brain region. This increased efflux is due to the effects of d-fenfluramine on the vesicular transporter that leads to impulse-independent extrusion of 5-HT into the synapse by the terminal membrane transporter. Although this action fits well with the hypophagic effects of 5-HT, the increased 5-HT release is possibly not responsible for the effects of d-fenfluramine. This doubt has emerged from studies such as those showing that neither a neurotoxic lesion of 5-HT neurons in the brain, nor depletion of neuronal transmitter stores by administration of the synthesis inhibitor, pCPA, prevents the reduction in food intake caused by d-fenfluramine (see Curzon, Gibson and Oluyomi 1997). Instead, a direct effect of this compound and/or its metabolite, norfenfluramine, on 5-HT receptors has been proposed. Another drug that reduces food intake through advancing satiety is the non-selective 5-HT/noradrenaline reuptake inhibitor, sibutramine. However sibutramine also increases thermogenesis by increasing metabolism in brown adipose tissue (BAT). An important distinction between the effects of sibutramine and d-fenfluramine is highlighted by microdialysis studies (Heal et al. These show that the rate of increase in 5-HT efflux in the region of the PVN, after administration of sibutramine, is slow, progressive and long-lasting. This is because it relies on the accumulation of extracellular 5-HT following the inhibition of its reuptake after impulse-dependent release. This time-course contrasts with the rapid and transient increase in 5-HT efflux which results from the fenfluramine type of impulse-independent release from nerve terminals. In fact, this rapid increase in 5-HT release is thought to underlie the serious adverse side-effects of d-fenfluramine that have led to its withdrawal from the clinic.

They are replenished by the synthesis of salts to promote lipid absorption purchase 100mg furosemide with amex. The loss of bile acid in feces acid pool may circulate 3 to 5 times a day; in a heavy eater furosemide 40 mg lowest price, is order 100 mg furosemide otc, therefore cheap 40 mg furosemide mastercard, an efficient way to excrete cholesterol. The intestine is nor- Absorbed bile salts are transported in the portal blood mally extremely efficient in absorbing the bile salts by car- bound to albumin or high-density lipoproteins (HDLs). Inflammation of the ileum uptake of bile salts by hepatocytes is extremely efficient. In can lead to their malabsorption and result in the loss of just one pass through the liver, more than 80% of the bile salts large quantities of bile salts in the feces. Once taken up by hepato- severity of illness, malabsorption of fat may result. The uptake of bile salts Bile salts in the intestinal lumen are absorbed via four is a primary determinant of bile salt secretion by the liver. First, they are absorbed throughout the entire small intestine by passive diffusion, but only a The Liver Secretes Bile Pigments small fraction of the total amount of bile salts is absorbed in this manner. Second, and most important, bile salts are ab- The major pigment present in bile is the orange compound sorbed in the terminal ileum by an active carrier-mediated bilirubin, an end-product of hemoglobin degradation in process, an extremely efficient process in which usually less the monocyte-macrophage system in the spleen, bone mar- than 5% of the bile salts escape into the colon. Hemoglobin is first converted teria in the terminal ileum and colon deconjugate the bile to biliverdin with the release of iron and globin. Biliverdin salts to form bile acids, which are much more lipophilic is then converted into bilirubin, which is transported in than bile salts and, thus, can be absorbed passively. The liver removes bilirubin from these same bacteria are responsible for transforming the the circulation rapidly and conjugates it with glucuronic primary bile acids to secondary bile acids (deoxycholic and acid. The glucuronide is secreted into the bile canaliculi lithocholic acids) by dehydroxylation.. In the small intestine, bilirubin glucuronide is poorly ab- 496 PART VII GASTROINTESTINAL PHYSIOLOGY point that it cannot be solubilized, it starts to crystallize, forming gallstones. Eventually, calcium deposits form in the stones, increasing their opacity and making them easily detectable on X-ray images of the gallbladder. INTESTINAL SECRETION The small intestine secretes 2 to 3 L/day of isotonic alkaline fluid. This secretion is derived mainly from cells in the crypts of Lieberkühn, tubular glands located at the base of intestinal villi. Of the three major cell types in the crypts of Lieberkühn—argentaffin cells, Paneth cells, and undiffer- entiated cells—the undifferentiated cells are responsible for intestinal secretions. Intestinal secretion probably helps maintain the fluidity of the chyme and may also play a role in diluting noxious agents and washing away infectious microorganisms. The HCO3 in intestinal secretions protects the intestinal mu- cosa by neutralizing any H present in the lumen. This is important in the duodenum and also in the ileum where bacteria degrade certain foods to produce acids (e. The fluid and electrolytes from intestinal secretions are usually absorbed by the small intestine and colon, but if secretion surpasses absorption (e. If uncontrolled, this can lead to the loss of large quantities of fluid and electrolytes, which can result in dehydration and electrolyte imbalances and, ulti- mately, death. Cholera toxin binds to the brush border mem- brane of crypt cells and increases intracellular adenylyl cyclase activity. The result is a dramatic increase in intra- cellular cAMP, which stimulates active Cl and HCO3 secretion into the lumen. Also present in intestinal secretions are various mucins (mucoproteins) secreted by goblet cells. Mucins are glyco- proteins high in carbohydrate, and they form gels in solution. They are extremely diverse in structure and are usually very large molecules. The mucus lubricates the mucosal surface and protects it from mechanical damage by solid food parti- cles.

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