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The pelvis and calyx of the kidney are common sites for the formation and retention of calculi (stones). Injury to the other organs does not lead to increased serum levels of amylase and lipase. Numerous microvilli on the apical surface of the 278 Chapter 19 superficial layer of cells retain a protective film of tears. Transporters (carriers): amino acids, glucose, vitamins, and other organic nutrients 4. Langerhans cells (like other professional antigen-presenting cells) degrade pathogenic proteins to 8 to 10 residue amino acid peptides within 122 Chapter 9 phagolysosomes. As you attempt to confirm this surprising information through independent study, you learn that cholangiocytes continuously monitor the flow of bile. The concentration of drug required to bind 50% of the receptor sites is denoted by the dissociation constant (Kd) and is a useful measure of the affinity of a drug molecule for its binding site on the receptor molecule. The other steps of endochondral bone formation (choices A, C, D, and E) appear to be normal in patients with achondroplasia. Lamotrigine has caused skin rashes and lifethreatening Stevens-Johnson syndrome or toxic epidermal necrolysis. The major cause of emphysema is cigarette smoking; however, it is also seen in younger patients with alpha-1-antitrypsin deficiency (genetic disease). Environmental factors the importance of environmental factors in the aetiology of asthma has been particularly evident in studies of populations that have migrated from one country to another. Macrophages also "present" foreign antigens to lymphocytes to initiate immune responses. Drugs for Acute Muscle Spasm Many drugs (eg, cyclobenzaprine, metaxalone, methocarbamol, orphenadrine) are promoted for the treatment of acute spasm resulting from muscle injury. None of the other antiarrhythmic drugs mentioned appears to have significant interactions with warfarin. Keywords: Kidney, collecting ducts 40 the answer is E: Thin segments of the loop of Henle. For a few drugs, age or disease-related differences in drug metabolism are significant. Echocardiography can assess the structure and dimension of the right heart chambers and the pulmonary artery pressure can be estimated from the velocity of the tricuspid regurgitation jet. Like most sedative-hypnotics, benzodiazepines are schedule-controlled, exhibiting dependence liability and the development of tolerance. Submucosal glands are also present in the esophagus (esophageal glands); however, unlike the esophagus, the mucosa shown in this image features intestinal villi lined by columnar epithelial cells (absorptive enterocytes). Sebum, the oily product of the sebaceous gland, is released following rupture of the cells. The mucus, produced by glands and goblet cells, coats the luminal surface over most of the conducting portion of the respiratory tract. Diagnosis depends on the doctor having a high level of awareness of the many presentations of tuberculosis and undertaking appropriate investigations. Thirst sensation is mediated by higher cortical areas, including the anterior cingulate cortex and the insular cortex. Antibody-mediated hemolysis liberates free hemoglobin that is degraded by proteases to peptides and heme (the porphyrin ring that binds iron). Colistin Bronchodilator medication Some patients with cystic fibrosis have a reversible component to their airway obstruction and benefit from bronchodilator drugs. Quinidine and disopyramide have similar effects but are used much less frequently. The lengths of the thin segment loops vary, depending on the location of their original nephrons. None of the other cells display the distinctive polymorphonuclear morphology of segmented neutrophils. This endocrine tissue normally develops after ovulation by morphological and functional changes in which of the following cells

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This glycosylated subtype of hemoglobin (hemoglobin A1c) is measured routinely to monitor the overall degree of hyperglycemia that occurred during the preceding 6 to 8 weeks. Although the other cells are found in diffuse and nodular lymphatic tissue, they do not form germinal centers in lymphoid follicles. Depending on the dose of iron, necrotizing gastroenteritis, shock, metabolic acidosis, coma, and death may result. Keywords: Renal cell carcinoma, renal corpuscle, glomerulus 16 the answer is C: Urinary pole of the Bowman capsule. Langerhans cells are mononuclear phagocytes derived from bone marrow precursor cells. Gap junction channels comprise two hemichannels (connexons) that align to form a communication pathway between two cells. It 88 Tuberculosis may occur following direct progression of the initial infection or result from endogenous reactivation of infection or from exogenous re-infection (inhalation of Mycobacterium tuberculosis from another infected individual) in a patient who has had previous contact with the organism and has developed a degree of specific immunity. This action can be obtained with the use of doses lower than those needed for analgesia. Patients remain on ciclosporin, prednisolone and azathioprine indefinitely and are at ongoing risk from two particular hazards: rejection and infection. The iris (choice B) is usually heavily pigmented, and the color of the iris is referred to as eye color. The epithelium that lines these ducts (arrows, shown in the image) exhibits which of the following patterns of morphology Agents that activate presynaptic 2 receptors on such neurons (eg, clonidine, methyldopa) decrease central noradrenergic activity, an action thought to result in decreased vasomotor outflow. Most of the atypical drugs cause less extrapyramidal dysfunction than standard drugs. None of the other cutaneous structures are continuous with the glassy membrane of the hair follicle. Although hypoxaemia, hypercapnia and elevation of pulmonary artery pressure occur during apnoeas, cor pulmonale is unusual unless there is concomitant lung disease. Flows through the anterior chamber and exits the eye at the "angle" formed between the iris and cornea 5. Ocular sarcoidosis often presents as pain and redness of the eye as a result of anterior 178 Interstitial lung disease treatment is available, but corticosteroids suppress inflammation in the affected organs, frequently improving local and systemic symptoms. In this example, secretory cells of the sebaceous gland Cell Biology initiate programmed cell death in order to release their intracellular stores of lipid and wax. Onset of action may be accelerated by the addition of sodium bicarbonate, which enhances intracellular access of these weakly basic compounds. None of the other mechanisms of inflammation and immunity explain the pathogenesis of delayed-type hypersensitivity. Keywords: Mucosa-associated lymphoid tissue, lamina propria 43 the answer is A: Intussusception. Thiazides such as hydrochlorothiazide are sometimes sufficient for mild chronic failure. None of the other proteins present antigenic peptides to helper T cells during B-cell activation. Contraction of smooth muscle cells in medium arteries helps maintain systemic blood pressure. The respiratory region is covered by a ciliated, pseudostratified columnar epithelium (respiratory epithelium). Hereditary hemochromatosis is an abnormality of iron absorption in the small intestine. The centre of an area of destructive pneumonia may break down to form a lung abscess, particularly when the pneumonia results from Staphylococcus aureus or Klebsiella pneumoniae. None of the other types of cell division describe the behavior of germ cells within ovarian follicles during fetal development. Increased hematocrit in this patient reflects hemoconcentration, secondary to fluid loss (severe diarrhea). Dexmedetomidine this centrally acting 2-adrenergic agonist has analgesic and hypnotic actions when used intravenously. The just-mentioned drugs have relatively little effect on dopamine receptors, but dopamine itself is a potent dopamine-receptor 76 agonist and, when given as a drug, can also activate receptors (intermediate doses) and receptors (larger doses).

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Microscopically, tubular adenomas exhibit closely packed epithelial tubules, which may be uniform or irregular with excessive branching. Lidocaine is commonly used topically to relieve skin itching and pain and as a local anesthetic prior to dental surgery. Accessory glands of the male reproductive tract include paired seminal vesicles, the prostate gland, and several bulbourethral glands. Keywords: Spleen, red pulp the arrow identifies 35 the answer is D: Myofibroblasts. Botulinum toxin is associated with improperly canned foods that are stored without refrigeration. The commercial manufacture of cigarettes started around 1900 and smoking soon became popular among men. Therefore, these antiarrhythmic drugs block channels in abnormal tissue more effectively than channels in normal tissue. The diagnosis may be confirmed by detecting Pneumocystis jirovecii in induced sputum or in bronchoalveolar lavage fluid. Keywords: Collagen, posttranslational modifications 14 the answer is D: Hydroxylation of proline and lysine residues. Carbonic anhydrase is also found in other tissues and plays an important role in the secretion of cerebrospinal fluid and aqueous humor. As discussed earlier, the basilar membrane is 286 Chapter 19 narrow and relatively stiff at the base of the cochlea but increases in width and decreases in stiffness as it coils toward the apex of the cochlea. Because convenience of administration is desirable for chronic therapy, doses should be given orally if possible and only once or a few times per day. Capillaries arising from the pulmonary arteries course through the alveolar septa, providing a rich blood supply to each alveolus. Stage 1: Analgesia In stage 1, the patient has decreased awareness of pain, sometimes with amnesia. Overdose is managed with intravenous naloxone or nalmefene and ventilatory support. Infection spread during this initial illness may lie dormant in any organ of the body. Propranolol, metoprolol, and timolol are commonly used as prophylactic drugs in patients who have had a myocardial infarction. Which of the following cells in the skin is responsible for the production of vitamin D3 Agents with low blood:gas solubility have a fast onset of action and a short duration of recovery. The endometrial biopsy shown for Question 37 shows evidence of interstitial edema (edematous stroma). In acute dystonias, parenteral administration of benztropine or diphenhydramine is helpful. Patients with ovarian cancer typically present with a history of increasing abdominal girth, owing to an accumulation of neoplastic cells and fluid within their peritoneal cavity. Interactions occur between older antihistamines and other drugs with sedative effects (eg, benzodiazepines and alcohol). Patients with end-stage liver disease often present with complications of portal hypertension, including ascites, splenomegaly, and bleeding esophageal varicose veins (varices). Examination 150 Chapter 11 of the tumor margin shows an intrapulmonary bronchus (shown in the image). Oxygen and nutrients move by passive diffusion into the overlying epithelium from capillaries in the lamina propria. Isosorbide dinitrate (like all the nitrates) and prazosin can cause reflex tachycardia.

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Which of the following drugs is established to be both effective and safe to use in a pregnant patient suffering from bipolar disorder The next definitive investigation to confirm the diagnosis is: A interferon gamma release assay B Mantoux test C Heaf test D bronchoscopy and bronchoalveolar lavage E gastric washings 7. Unless these patients receive adequate pancreatic enzyme supplements, they develop steatorrhoea with frequent bulky offensive stools and failure to gain weight. Which of the following syndromes is this patient most likely to exhibit as a result of this drug overdose Leukopenia may also be caused by typhoid fever and certain viral and rickettsial infections. L-type Ca2 channels (dihydropyridine receptors) open to create a Ca2 -trigger flux. What are the advantages and disadvantages to using gap junctions in signal propagation Most act on receptors on the extracellular face of the cell membrane and modify the intracellular function of those receptors by transmembrane signaling Receptors are in dynamic equilibrium, being synthesized in the interior of the cell, inserted into the cell membranes, sequestered out of the membranes, and degraded at various rates. Keywords: Epiphyseal growth plate, endochondral bone formation 47 the answer is A: Cartilage growth plates. Loops of Henle are straight tubules that extend deep into pyramids of the renal medulla. Explain how hyperkalemia, hypokalemia, or an antiarrhythmic drug can cause an arrhythmia. Alpha1-selective-Prazosin is a highly selective, reversible pharmacologic 1 blocker. The distribution of mitochondria and microfilaments is examined by confocal fluorescence microscopy (shown in the image). Peg cells are so named because they resemble tiny pegs pounded into the epithelium lining the uterine tubes. Although, in clinical practice, patients with asthma are sometimes classified as having atopic asthma (occurring in relation to inhalation of environmental antigens in a susceptible person) or non-atopic asthma (occurring without any definable relationship to an environmental antigen), the pathological features of the airway inflammation are identical. Asthma in this patient is a chronic lung disease caused by increased responsiveness of the airways to a variety of stimuli. Sharing resources helps coordinate the progression of germ cells through the stages of spermatogenesis and spermiogenesis. The spiral limbus represents a thickened periosteum of the osseous spiral lamina on the medial aspect of the scala media (indicated by the asterisk). On the basis of a set of baseline serum lipid values, propose a rational drug Argue the merits of combined drug therapy for some diseases, and list 3 rational drug combinations. It is likely that the inflammatory cascade of asthma can be initiated by a variety of different factors in different patients. The blood smear displays elliptical erythrocytes, as well as a normal segmented neutrophil. Clinical use-Selegiline has minimal efficacy in parkinsonism if given alone but can be used adjunctively with levodopa. Patients with cystic fibrosis also have abnormal mucus glycoproteins, which act as binding sites such that bacteria adhere to the mucosa and proliferate. In living tissue, the cortex takes on a reddish brown color, since most of the blood in the renal arteries is delivered to the cortex (90% to 95%). Epinephrine and norepinephrine are stored in dense core granules within chromaffin cells of the adrenal medulla. Axons carry nerve signals away from neuronal cell bodies, whereas dendrites convey signals inward toward neuronal cell bodies. Cystic medial necrosis and dissecting aneurysms are typically diseases of the aorta (choices C and D). These studies are particularly useful in identifying previously unrecognised causes of occupational asthma but they should only be undertaken in specialist units, as they are potentially hazardous. This melanoma typically arises in the palm of the hand, sole of the foot, or in a subungual (nail bed) location. Legitimate indications include narcolepsy and, with appropriate adjuncts, weight reduction.

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A 74-year-old retired mechanic is admitted with a myocardial infarction and a severe acute cardiac arrhythmia. Examination of a skin biopsy suggests the diagnosis of pemphigus vulgaris (shown in the image). An increase in upper airway resistance, such as that found in nasal obstruction. They are relatively selective and have no significant blocking actions at H1 or autonomic receptors. Keywords: Presbyopia, visual accommodation 25 the answer is A: Accumulation of sorbitol in the lens. Abnormalities of bile secretion and absorption cause an increased incidence of gallstones and biliary cirrhosis. Contractions of myoid cells in the peritubular connective tissue help to propel the male gametes on Male Reproductive System their journey through the excurrent duct system. Keywords: Integrins, microfilaments, cell adhesion 13 19 the answer is E: Pinocytosis. The other cells process and/or present antigens, but they are not located in the skin. Inevitably, patients will experience such emotions as shock, anger and denial, and the doctor must work through these with them. Which of the following terms best describes the material filling the lumens of the follicles shown in the image The secretory cells in apocrine sweat glands are simple cuboidal and eosinophilic. A formulation combining levodopa, carbidopa, and entacapone is available, simplifying the drug regimen. Selective anticonvulsant action (ie, suppression of convulsions at doses that do not cause severe sedation) occurs with only a few of these drugs (eg, phenobarbital, clonazepam). Bile contains water, various electrolytes, bile salts, cholesterol, fatty acids, phospholipids, and bilirubin. Side effects include nausea (common), headache, difficulty sleeping and abnormal dreams. Which of the following terms describes the glandular epithelial cells shown in the image Your 37-year-old patient has been diagnosed with a rare metastatic carcinoid tumor. Astrocytes (choice A) and oligodendrocytes (choice C) are neuroglial cells of the central nervous system. A diagnosis of meconium ileus equivalent (distal intestinal obstruction syndrome) was made and she was treated with Gastrografin (orally and by enema), N-acetylcysteine (orally) and intravenous fluids, followed by flushing of the bowel using balanced intestinal lavage solution. Their dendrites synapse with hair cells of the spiral organ, and their axons form the auditory nerve that extends into the central nervous system. The large cells with 31 A 46-year-old man with malignant glioblastoma develops cardiorespiratory failure and expires. Hemidesmosomes connect the basal membranes of Sertoli cells to their underlying basal lamina. All other effective therapies, particularly inhaled steroids, should be continued at full dose. Pernicious anemia is an autoimmune disorder in which patients develop autoantibodies against parietal cells and intrinsic factor.

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Which of the following abnormalities accounts for the pathogenesis of cataracts in this patient In addition to absorption, secretion, and protection, epithelial cells provide receptors for the special sense organs. The primary visual cortex is situated in and around the calcarine sulcus, a deep cerebral infolding along the medial aspect of the occipital lobe. Local Integration Local feedback control has been found at the level of the nerve endings in all systems investigated. A drug that increases metabolism (clearance) of the anticoagulant lowers the steady-state plasma concentration (both free and bound forms), whereas one that displaces the anticoagulant increases the plasma level of the free form only until elimination of the drug has again lowered it to the steadystate level. A sample of the biopsy should also be sent for culture for Mycobacterium tuberculosis. Gastrointestinal system-Irritation, inflammation, bleeding, and scarring of the gut wall occur after chronic heavy use of ethanol and may cause absorption defects and exacerbate nutritional deficiencies. Verapamil is an inhibitor of P-glycoprotein drug transporters and has been used to enhance the cytotoxic actions of methotrexate in cancer chemotherapy. Which of the following structures is primarily affected in this superficial punctate keratopathy None of the other choices describe increased numbers of normal squamous epithelial cells in the epidermis. Aspiration of this fluid will reveal an abundance of which of the following inflammatory cells Pulmonary embolism is a leading cause of maternal death and accurate diagnosis is essential. Keywords: Thyroid gland, follicular cells 30 the answer is D: Basolateral membranes of follicular epithelial cells. The diluting ability of the nephron is reduced because the loop of Henle is the site of significant dilution of urine. The triptan derivatives are now considered preferable to the ergots because of lower toxicity. Atherosclerosis is the most common acquired abnormality of large- and medium-sized arteries. As sleep becomes more shallow (often without waking completely), the improved muscle tone relieves the obstruction and terminates the apnoea. Varicocele (choice E) represents a local dilation of testicular veins and presents as nodularity on the lateral side of the scrotum. The instructor asks you to identify the type of epithelium that is shown in the image. This benefit of blockers had long been recognized in patients with hypertrophic cardiomyopathy but has also been shown to occur in patients without cardiomyopathy. In the past, the nitrates were responsible for several occupational diseases in explosives factories in which workplace contamination by these volatile chemicals was severe. Almost all drugs (or their metabolites) are eventually excreted, but for many, excretion occurs only some time after they have been metabolized to inactive products A large number of drugs alter their own metabolism and the metabolism of other drugs either by inducing the synthesis of larger amounts of the metabolizing enzymes (usually P450 enzymes in the liver) or by inhibiting those enzymes. Harmful effects of sunlight exposure on the skin include inhibition of metabolism, generation of reactive oxygen species, activation of programmed cell death, mutagenesis, and cancer. Prolonged anaerobic blood culture is required to identify the organism, which is sensitive to metronidazole. In contrast, local aerosol administration of surface-active corticosteroids (eg, beclomethasone, budesonide, dexamethasone, flunisolide, fluticasone, mometasone) is relatively safe, and inhaled corticosteroids have become common first-line therapy for individuals with moderate to severe asthma. The fluid is then concentrated, and made hyperosmotic, via a countercurrent multiplier system. Characteristically, vomiting is followed by chest pain and subcutaneous emphysema (palpable air in skin) as air and gastric contents leak into the mediastinum. Most antiseizure drugs are metabolized by hepatic enzymes (exceptions include gabapentin and vigabatrin), and in some cases active metabolites are formed. Active screening is, of course, only worthwhile if there is a therapeutic option available.

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Anterograde transport: Vesicles filled with transmitters and other materials attach to the tubule arrays and are then moved toward the terminals by kinesin, a molecular motor. The -receptor activation plays a major role in the respiratory depressant actions of opioids and together with -receptor activation slows gastrointestinal transit; -receptor activation also appears to be involved in sedative actions; -receptor activation may play a role in the development of tolerance. Cytoskeletal proteins include microtubules (composed of tubulin), microfilaments (composed of actin), and intermediate filaments (composed of tissue-specific filamentous proteins). Fever stimulus In both, temperature increase occurs: In fever, regulation drives the increase, whereas during heat stress, heat gain drives it, and regulation is attempting to counteract it. Recent clinical trials have shown a small clinical improvement in some patients receiving ataluren, although this did not reach statistical significance. This muscle layer characterizes the bronchopulmonary tree as far distally as the alveolar ducts, where smooth muscle fibers are observed as knoblike structures within interalveolar septa. Gestational trophoblastic disease is characterized by abnormal proliferation of the trophoblast. Even after stopping, lung function will continue to decline at (something like) the natural age-related rate. The identification of the specific genes (or groups of genes) that affect drug responses is still incomplete, but knowledge about a small number of these genes of pharmacologic significance has suggested the possibility that "personalized medicine" is possible and may become practical in the near future. They also inhibit the uptake of adenosine by endothelial cells and erythrocytes and thereby increase the plasma concentration of adenosine. When the tumour is confined to one lobe, surgical resection is the treatment of choice. In cryptogenic organising pneumonia, histology shows intra-alveolar buds of organising fibrosis. In severe liver disease, stores of glucuronide, sulfate, and glutathione may be depleted, making the patient more susceptible to hepatic toxicity with near-normal doses of acetaminophen. Which of the following cytologic features characterizes the epithelial cells that line this portion of the excurrent duct system The major processes involved in pharmacokinetics are absorption, distribution, and elimination. Note also that decreased blood pressure evokes the baroreceptor reflex, resulting in strong compensatory sympathetic discharge to the heart. The interstitium that is deep in the medulla, at the apex of the renal pyramid, is hyperosmotic (approximately four times the osmolality of plasma). The therapeutic window, a more clinically useful index of safety, describes the dosage range between the minimum effective therapeutic concentration or dose, and the minimum toxic concentration or dose. Mitochondria have inner and outer membranes that provide compartments for the enzymes and cytochromes that mediate glycolysis and oxidative phosphorylation. Nodular hyperplasia of the prostate is a common disorder characterized clinically by enlargement of the gland and obstruction to the flow of urine through the bladder outlet, and pathologically by the proliferation of glands and stroma. High concentrations of enflurane may cause spike-and-wave activity and muscle twitching, but this effect is unique to this drug. Mucin-secreting mucosal glands may be seen in the neck of the gallbladder; however, the epithelial structures identified in this image are not composed of mucous cells. Patients also benefit in this context from being on appropriate inhaled medication. Mutations in the genes for the outer dense fiber and fibrous sheath proteins lead to abnormal sperm morphology and infertility. Motile cilia generate a mucociliary ladder that removes inhaled particles from the lungs, whereas immotile cilia provide mechanoreceptors that monitor gravity and acceleration in the ear. These paired images contrast normal bone marrow (image on left) with hyperplastic bone marrow (image on right) from a patient living at high altitude. Paneth cells synthesize and secrete a variety of antibacterial substances, including lysozyme and defensin. Genes for an inner mitochondrial membrane protein and a red fluorescent protein are spliced, and the fusion protein is expressed in mouse embryo fibroblasts. They invaginate and migrate to form the three primary germ layers: ectoderm, mesoderm, and endoderm.