Cough Case 5

A 14-year-old girl receives a bone marrow transplant as part of her treatment for acute lymphoblastic lymphoma. During the period of profound immunosuppression before the marrow engrafts, she develops nonproductive cough, fever, mild hemoptysis, and pleuritic chest pain. A plain chest x-ray film shows a pleuraI-based wedge-shaped lesion with focal cavitation. Open chest lung biopsy reveals necrosis and hemorrhage.
Septate fungal forms with dichotomous 45-degree branching are seen in the necrotic areas and involving the walls of several blood vessels.
When the fungus is cultured, it is found to be a monomorphic fungus.

Q 1

Which of the following is a monomorphic filamentous fungus?

/ A. Aspergillus
/ B. Blastomyces
/ C. Coccidides
/ D. Histoplasma
/ E. Sporothrix

Q 2
Two commonly encountered invasive fungi are Aspergillus and Candidia. In tissue specimens, which of the following features is often helpful in distinguishing these organisms?

/ A. Aspergillus has both hyphae and pseudohyphae
/ B. Aspergillus has budding yeasts
/ C. Aspergillus has germ tubes
/ D. Aspergillus shows dichotomous branching
/ E. Aspergillus shows generally obtuse angles of branching

Q 3

Involvement by this patient's infection of which of the following is considered to have the worst prognosis?
/ A. Brain
/ B. Lung
/ C. Middle ear
/ D. Sinus
/ E. Skin

Q 4
Which of the following is the most appropriate pharmacotherapy for this patient?
/ A. Amphotericin B
/ B. Clotrimazole
/ C. Fluconazole
/ D. Flucytosine
/ E. Griseofulvin

Q 5

Which of the following best describes the mechanism of action of the most appropriate medication for this patient's disease?
/ A. Forms pores in fungal membranes
/ B. Inhibits the demethylation of lanosterol
/ C. Inhibits squalene epoxidase
/ D. Inhibits thymidylate synthase
/ E. Interferes with the synthesis of ergosterol

Q 6

Toxicity to which of the following organs is most likely to limit the administration of the most appropriate medication for this patient's disease?
/ A. Brain
/ B. Heart
/ C. Kidney
/ D. Liver
/ E. Lung

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Cough Case 5 Answers
A1
The correct answer is A. The fungi that cause "deep infections" in humans are subdivided into the dimorphic forms (which, depending upon temperature, can be either yeast forms or hyphal forms) and the monomorphic forms (which grow in the same general form at different temperatures). Of the fungi listed, only Aspergillus is monomorphic. Aspergillus is a common saprophytic mold found on decaying material in the environment throughout the world. It can cause human diseases, including allergic bronchopulmonary aspergillosis (which is essentially an allergic reaction to inhaled Aspergillus conidia or spores), fungus ball (in which the Aspergillus grows without invading in a preexisting cavitary lesion of the lung), invasive aspergillosis (including pneumonia, meningitis, and other systemic infections), and cellulitis. Invasive aspergillosis is most often seen in severely immunocompromised patients with severe neutropenia, notably including those with a history of transplantation, chronic granulomatous disease, and leukemia. This patient's presentation is typical for invasive pulmonary aspergillosis. The other fungi listed (choices B, C, D, and E) are all dimorphic.

A2
The correct answer is D. Aspergillus has hyphae, but not pseudohyphae, budding yeasts, or germ tubes. The branching is dichotomous and at an acute (often about 45 degrees) angle (opposite of choice E).
Characteristics to look for with Candida include both pseudohyphae and true hyphae (choice A), budding yeasts (choice B), and occasionally germ tubes (choice C, better seen with some culture methods).

A3
The correct answer is A. Cerebral aspergillosis is a feared complication of other forms of aspergillosis because most patients die despite appropriate antifungal therapy. Of the other sites listed in the question choices, true invasive infection of the lung (choice B), as opposed to a fungus ball, is considered the most serious site of infection, though less so than infection of the brain.
Middle ear and sinus involvement (choices C and D) become clinically worrisome when dissemination or extension to the brain occurs.
Skin involvement (choice E) is worrisome if dissemination occurs.

A4
The correct answer is A. Amphotericin B is the mainstay of therapy of invasive aspergillosis. This medication has a wide fungicidal spectrum and remains either the drug of choice or the co-drug of choice for severe infections caused by Aspergillus, Candida, Cryptococcus, Histoplasma, Mucor, and Sporothrix. Alternative antifungal agents that are not the preferred therapy but do have some activity against aspergillus include itraconazole, flucytosine (choice D), and voriconazole.
Clotrimazole (choice B) is used topically for candidal and dermatophytic infections.
Fluconazole (choice C) is the drug of choice for esophageal and invasive candidiasis and coccidioidomycosis, and is used for prophylaxis and suppression in cryptococcal meningitis.
Flucytosine (choice D) is also synergistic with amphotericin B in candidiasis and cryptococcosis.
Griseofulvin (choice E) is given orally, but is active only against dermatophytes.

A5
The correct answer is A. The polyene anti-fungal amphotericin B is an amphoteric compound, with both polar and non-polar structural elements, that interacts with ergosterol in fungal membranes to form artificial "pores," which disrupt membrane permeability. Resistant fungal strains are those that appear to have low ergosterol content in their cell membranes. Amphotericin B is given by slow IV infusion and penetrates poorly into the central nervous system (intrathecal injections can be used). It has a half-life of more than 2 weeks and is removed by both metabolism and renal elimination.
Antifungal agents in the azole class (including ketoconazole, fluconazole, and itraconazole) interfere with the synthesis of ergosterol (choice E) by inhibiting the P450-dependent 14-alpha-demethylation of its precursor molecule, lanosterol (choice B).
Flucytosine is activated by fungal cytosine deaminase to 5-fluorouracil (5-FU), which can be incorporated into fungal RNA and can be also used to form 5-fluorodeoxyuridine monophosphate, which in turn inhibits thymidylate synthase (choice D) and the synthesis of thymine.
The anti-dermatophytic drug terbinafine inhibits squalene epoxidase (choice C) and thus decreases ergosterol synthesis (choice E).

A6
The correct answer is C. Nephrotoxicity is most likely to be dose-limiting, and may force amphotericin treatment to end prematurely. This is an important problem, since we have so few drugs with wide spectrum activity against invasive fungal organisms. An amphotericin B lipid complex (ABLC, Abelcet) that may be less nephrotoxic in those patients who cannot tolerate conventional amphotericin is available. Amphotericin B also causes infusion-related reactions including fever, chills, nausea, vomiting, headache, generalized malaise, hypotension, and arrhythmias.
Major problems encountered less commonly than renal toxicity include anaphylaxis, generalized pain, bone marrow toxicity, rash, a variety of cardiac problems including cardiac arrest (choice B), liver failure (choice D), pulmonary edema (choice E), and convulsions (choice A).

Cough Case 4

A 72-year-old woman presents to the emergency department with cough, fever, and shortness of breath. The woman lives alone at home, but spends part of each day shopping and riding public buses. Approximately 4 days previously she had developed an upper respiratory infection.
Approximately 2 days ago, she abruptly became much more ilI, and her symptoms started worsening, beginning with a single, Iong, shaking chill. Since that time, she has had fever, pain with breathing, cough, and dyspnea. She decided to come to the emergency department when
her temperature at home was 103.4 F. In the emergency department, her temperature is 39.9 C (103.8 F), blood pressure is 90/50 mm Hg, pulse is 120/min, and respirations are 30/min. No breath sounds are heard over her lower left lung field, but they can be heard at other sites.

Q 1

A chest x-ray film would be most likely to demonstrate which of the following:
/ A. A single roughly ovoid white area
/ B. Complete whitening over one lobe of her lungs
/ C. Marked dilation and elongation of bronchial spaces
/ D. Multiple small spotty areas of white found primarily near the bronchi
/ E. No obvious radiologic changes

Q 2
Gram's stain of a smear from a sputum sample demonstrates gram-positive lancet-shaped diplococci in short chains. Which of the following
would most likely be identified after culturing?

/ A. Chlamydia pneumoniae
/ B. Haemophilus influenzae
/ C. Legeonella pneumophila
/ D. Staphylococcus aureus
/ E. Streptococcus pneumoniae

Q 3
Which of the following is thought to contribute to the ability of gram-positive organisms to retain the Gram's stain during the decolorization
process?
/ A. Large periplasmic space
/ B. Presence of capsule
/ C. Presence of outer membrane
/ D. Presence of pili
/ E. Thick peptidoglycan layer

Q 4
Which of the following is a characteristic feature on culture of this patient's organism?
/ A. AIpha-hemolytic colonies inhibited by optochin on blood agar and lysed by bile
/ B. Beta-hemolytic colonies that are bacitracin-resistant on blood agar
/ C. Beta-hemolytic colonies that are inhibited by bacitracin on blood agar
/ D. Catalase-negative organisms that hydrolyze esculin in 40% bile and 6.5% NaCI
/ E. Catalase-positive, coagulase-positive organisms that cause beta-hemolytic, yellow colonies on blood agar

Q 5
At this stage of the disease (two days following onset of first symptoms), and before treatment is started, what are the expected histopathologic findings in the affected lung parenchyma?
/ A. Advanced organization with macrophages and fibroblasts
/ B. Interstitial lymphomonocytic inflammatory infiltration
/ C. Intra-alveolar purulent exudate admixed with erythrocytes
/ D. Resolution of inflammatory exudate with semifluid debris
/ E. Vascular congestion without intra-alveolar exudation

Q 6
The patient's infection is treated with parenteral penicillin, to which she promptly responds. This drug acts by which of the following mechanisms?
/ A. Inhibits bacterial protein synthesis
/ B. Inhibits growth of cell walls
/ C. Interferes with bacteriaI DNA synthesis
/ D. Interferes with folate metabolism
/ E. Punches holes in cell membranes

Q 7
A few minutes after the patient receives the antibiotic therapy, she develops an adverse reaction characterized by an itchy skin eruption and
acute respiratory distress. This reaction is most likely attributable to which of the following mechanisms?
/ A. Antibody-mediated cellular dysfunction
/ B. Complement-dependent reaction
/ C. Delayed-type hypersensitivity
/ D. IgE-mediated mast cell degranulation
/ E. Immune-complex deposition

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Cough Case 4 Answers
A1
The correct answer is B. This patient has lobar pneumonia, which is seen radiologically as a complete whitening of one or more lobes of the lungs.
Choice A describes the appearance of a mass lesion of the lung, such as tumor or tuberculosis
Choice C describes the radiologic changes accompanying bronchiectasis.
Choice D describes the radiologic appearance of bronchopneumonia, rather than lobar pneumonia.
While very early in lobar pneumonia, no obvious radiologic changes may be seen (choice E), this patient's lack of breath sounds over the lower left lung field indicates that her pneumonia is past this very early stage.

A2
The correct answer is E. Streptococcus pneumoniae is the most commonly identified causative organism for bacterial pneumonia. Up to two-thirds of bacteremic community-acquired pneumonias are due to this organism. 5-25% of healthy individuals carry S. pneumoniae in their pharynx. The classic description of S. pneumoniae on Gram's stain is that given in the question stem. S. pneumoniae can be verified by the Quellung reaction, or counterimmunoelectrophoresis to determine serotypes of isolated strains or for case detection using sputum specimens (there are more than 80 distinct serotypes based on studies of capsular antigens).
Chlamydia pneumoniae(choice A) is not identified on the basis of Gram's stain, but rather, can be seen with Giemsa or immunofluorescence.
Haemophilus influenzae(choice B) and Legionella pneumophila(choice C) are gram-negative rods.
Staphylococcus aureus(choice D) is also a gram-positive coccus, but the classic description of this organism typically includes a reference to "grape-like clusters."

A3
The correct answer is E. The peptidoglycan layer in the cell wall of gram-positive organisms is much thicker than that in gram-negative organisms, and is thought to contribute to the gram-positive staining reaction.
A large periplasmic space (choice A) and an outer membrane (choice C) are characteristics of gram-negative cell walls.
Capsules (choice B) can be seen in both gram-positive and gram-negative species.
Pili (choice D) are small hair-like structures that are most often seen in gram-negative organisms.

A4
The correct answer is A. These findings are used to identify Streptococcus pneumoniae. Optochin sensitivity is used to differentiate the viridans streptococci (resistant) from S. pneumoniae (sensitive). Another test used to identify S. pneumoniae is the Quellung reaction. The only medically important optochin-sensitive organism that gives a positive Quellung reaction is S. pneumoniae.
Choice B is seen with Streptococcus agalactiae.
Choice C is seen with Streptococcus pyogenes.
Choice D is seen with Enterococcus faecalis.
Choice E is seen with Staphylococcus aureus.

A5
The correct answer is C. Acute lobar pneumonia has classically been subdivided into four pathologic stages. The initial stage of congestion(choice E) lasts less than 24 hours and is characterized by engorgement of vessels, with intra-alveolar fluid containing few cells, but often, numerous bacteria. Over the following few days, an exuberant intra-alveolar exudate of red cells, neutrophils, and fibrin develops, heralding the stage of red hepatization (choice C; so-called because the lung resembles liver at this stage). During the last half of the first week of illness, the red cells begin to break down, but a fibrinous exudate remains in the alveoli; this is the stage of gray hepatization. If death does not supervene, resolution (choice D) occurs in the second week in untreated cases, with digestion of the exudate to leave semifluid debris that are phagocytized, or coughed up. In some cases, the exudate, rather than resolving in this manner, undergoes further organization (choice A).
An interstitial lymphomonocytic infiltrate (choice B) is characteristic of primary atypical pneumonia, caused by Mycoplasma or viruses.

A6
The correct answer is B. The penicillins and cephalosporins both inhibit cell wall synthesis. Penicillin G is the preferred antibiotic for sensitive strains; 25% of strains are resistant and can be treated with cephalosporins, erythromycin, and clindamycin. Pneumococcal pneumonia can be prevented in a number of cases; the pneumococcal vaccine contains 23 specific polysaccharide antigens found in 85-90% of the serious pneumococcal infections.
Inhibitors of bacterial protein synthesis (choice A) include aminoglycosides, chloramphenicol, macrolides, and tetracycline.
Inhibitors of nucleic acid synthesis (choice C) include fluoroquinolones and rifampin.
Inhibitors of folic acid synthesis (choice D) include sulfonamides, trimethoprim, and pyrimethamine.
Agents that disrupt cell membranes (choice E) include azole and polyene antifungal agents.

A7
The correct answer is D. This patient has had an acute allergic reaction to the antibiotic, which can be further classified as an immediate hypersensitivity reaction. These reactions are mediated in a way similar to hay fever, with preformed IgE binding to the antibiotic antigen, and then the antigen-antibody complex triggering degranulation of mast cells with release of histamine and other active substances. These substances then cause both the itchiness of the skin and the bronchospasm that caused the respiratory distress.
An example of a disease caused by antibody-mediated cellular dysfunction (choice A) is Graves disease, in which antibodies to the TSH receptor cause a non-physiologic chronic stimulation of thyroid epithelial cells.
An example of a complement-dependent reaction (choice B) is hemolytic disease of the newborn.
An example of delayed-type hypersensitivity (choice C) is the tuberculin reaction.
An example of an immune complex deposition disease (choice E) is the vasculitis seen in systemic lupus erythematosus.

Cough Case 3

A 60-year-old man presents to the emergency department complaining of shortness of breath, cough, and copious sputum production. He states that he has been coughing for years, and has had increased sputum production for several months each year. On examination, he is
obese, afebrile, cyanotic, and in acute distress. Coarse rales are auscultated bilaterally at the lung bases. He smokes two packs of cigarettes a day and has a seventy-five pack-year smoking history. A chest x-ray film appears normal, except for slightly enlarged lung fields.

Q 1

Which of the following is the most likely diagnosis?
/ A. Chronic bronchitis
/ B. Emphysema
/ C. Myocardial infarction
/ D. Pneumonia
/ E. Pulmonary embolus

Q 2
As this patient waits in the emergency department, his condition begins to deteriorate. He turns increasingly blue and an arterial blood gas is drawn. His PO2 is 45 mm Hg, which under normal conditions means that his hemoglobin would be 75% saturated. Which of the following
mechanisms could cause a hemoglobin saturation of less than 75% at this pO2?
/ A. Decreased 2,3-DPG Ievels
/ B. Decreased hemoglobin
/ C. Decrease in body temperature
/ D. Decreased PCO2
/ E. Decreased serum pH

Q 3
Why must care be exercised when administering O2 to this patient?
/ A. Administering O2 washes out alveolar CO2 and inhibits respiration
/ B. Chronic hypoxia alters the blood-brain barrier such that CO2 cannot diffuse into the medullary apneustic center
/ C. Chronic hypoxia induces atrophy in the dorsal respiratory group in the medulla
/ D. Increased PO2 worsens CO2 retention by decreasing respiratory drive
/ E. O2 is acutely toxic to the chronically hypoxic alveolar epithelium

Q 4
The mucus seen in this patient is derived from which of the following cell types?
/ A. Alveolar macrophages
/ B. Goblet cells
/ C. Neuroendocrine cells
/ D. Type l pneumocyte
/ E. Type ll pneumocyte

Q 5
Which of the following spirometry profiles would most likely be seen in this patient?
/ A. Decreased TLC, decreased FEV1
/ B. Decreased TLC, decreased RV
/ C. Decreased TLC, increased FEV1
/ D. EIevated TLC, decreased FEV1
/ E. NormaI TLC, decreased FEV1

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Cough Case 3 Answers


A1
The correct answer is A. This patient has findings classic for the "blue bloater" of chronic bronchitis. Patients with chronic bronchitis have excessive tracheobronchial mucus production sufficient to cause cough with expectoration for at least three months of the year for more than two consecutive years. "Blue bloaters" are named for their obese body habitus, copious sputum production, and cyanotic episodes. This condition may occur initially without airway obstruction, but eventually, most patients progress to obstructive disease.
Patients with emphysema (choice B) represent another form of COPD. They are known as "pink puffers" because they do not become cyanotic until they decompensate. They display a thin body habitus and belabored breathing. This patient is not consistent with the pink puffer of emphysema.
This patient does not have the classic findings for myocardial infarction (choice C), which include: chest pressure or pain, shortness of breath, and/or pain that radiates to the jaw or left arm.
It is unlikely that this patient has pneumonia (choice D). Patients with pneumonia have cough with purulent sputum production, but they are usually febrile and have chest x-ray opacities.
While the diagnosis of pulmonary embolus (choice E) is elusive due to its varied presentations, it is unlikely that this patient has a pulmonary embolus. Findings for PE include pleuritic chest pain, shortness of breath, hemoptysis, and a history of calf pain indicative of deep vein thrombosis.

A2
The correct answer is E. A decrease in pH (an increase in H+ concentration) decreases the affinity of hemoglobin for O2. This facilitates unloading of oxygen from hemoglobin to the tissues. Choices A, C, and D increase the affinity of hemoglobin for O2, and thus cause the Hb to retain the O2.
Choice B is a distracter

A3
The correct answer is D. In a patient with normal respiratory function, the PCO2 and pH of cerebrospinal fluid drives the respiratory center in the medulla oblongata. As serum PCO2 rises, increased CO2 diffuses across the blood-brain barrier. When this CO2 is buffered with the high HCO3- of cerebral spinal fluid, the concentration of H+ rises accordingly. The chemosensitive cells in the medulla's respiratory center respond to this localized decrease in pH by stimulating ventilation. The pH in the CSF returns to nearly normal, more quickly than the renal compensation of the arterial pH, which takes 2-3 days. Patients with chronic CO2 retention will have an abnormally low ventilation for their PCO2 because the pH of their CSF is nearly normal. Therefore, in patients with chronic CO2 retention, arterial hypoxemia becomes their primary ventilatory stimulus. When the patient is given supplemental O2, the PO2 rises, and the hypoxic stimulation disappears, and respiration can become markedly depressed. The PCO2-dependent respiratory drive does not revert immediately, and thus the patient hypoventilates and retains CO2, which may precipitate coma, stupor, or death.
Administering O2 at high flow rates (choice A) may wash out alveolar CO2, but this is not the mechanism for hypoventilation of the chronically hypoxic patient.
Chronic hypoxia does not alter the diffusing capacity of the BBB (choice B).
Chronic hypoxia does not cause the respiratory center to atrophy (choice C).
Chronically high O2 concentrations can damage the alveolar epithelium, but in the acute setting, it does not alter its diffusion capabilities (choice E).

A4
The correct answer is B. In chronic bronchitis, goblet cell hyperplasia is seen in the airways. This hyperplasia, caused by chronic irritation (usually by tobacco smoke), results in increased mucus secretion and formation of mucus plugs. These mucus plugs obstruct the airways, and are responsible for part of the obstructive component of chronic bronchitis. Some degree of loss of elastic recoil of the airways is also seen and further adds to the obstructive component of the disease.
Alveolar macrophages (choice A) do not secrete mucus. They have a phagocytic function.
Neuroendocrine cells (choice C) are present in the respiratory tract. They are the cell of origin for oat cell carcinomas, and the neuroendocrine capabilities of these cells become evident with the paraneoplastic syndromes seen in this high-grade carcinoma.
Type I pneumocytes (choice D) comprise the majority of alveolar epithelium. They provide the majority of the surface area on which gas exchange occurs.
Type II pneumocytes (choice E) secrete the alveolar surfactant that allows alveoli of different diameters to inflate at the same pressure.

A5
The correct answer is E. Patients with chronic bronchitis tend to have normal TLC and decreased FEV1. Patients with chronic bronchitis do not typically have the increased TLC that their counterparts with emphysema have. They may however, have a modestly increased residual volume due to air trapping distal to mucus plugs. Similarly these mucus plugs obstruct the airways, creating the obstructive component of chronic bronchitis. Hence a decreased FEV1 is noted.
Choices A and B are not typical of any common pulmonary disorder.
Choice C is consistent with restrictive lung disease. The increased fibroelastic elements in the lung parenchyma decrease the lung capacity, while allowing the airways to remain open at increasingly lower pressures. Thus, a decreased TLC is seen with an increased FEV1.
Choice D is consistent with emphysema. These patients have destruction of the fibroelastic elements of the lung. As a result, the TLC increases. With decreased elastic tissue, the airways collapse at higher airway pressures, and a decreased FEV1 is seen.

Cough Case 2

A 70-year-old man is seen by his family practice physician during a routine office visit. The man complains of not feeling well for the last three months. Further questioning reveals that the patient has a chronic, unproductive cough that he attributes to an old smoking history. Physical
examination is notable for a 15-pound weight loss since the last office visit three months previously. A multinodular infiltrate is seen in the lung field behind and above the right clavicle.

Q 1

The patient is injected intradermally with PPD. 3 days after the injection, there is a 13-mm diameter area of induration at the injection site. This reaction is an example of which of the following types of immune response?
/ A. Type l hypersensitivity
/ B. Type ll hypersensitivity, cytotoxic subtype
/ C. Type ll hypersensitivity, noncytotoxic subtype
/ D. Type lll hypersensitivity
/ E. Type IV hypersensitivity

Q 2
Which of the following principally mediates this form of hypersensitivity?
/ A. Cytotoxic T cells, TH1 cells, and macrophages
/ B. IgE, basophils, and mast cells
/ C. IgG and complement
/ D. IgG, IgM, neutrophils, and macrophages
/ E. IgG, IgM, neutrophils, macrophages, and natural killer cells

Q 3
The strongest definitive identification of the pathogen responsible for this patient's disease would be provided by a positive result on which of the following biochemical tests?
/ A. Arylsulfatase
/ B. Heat-stable catalase
/ C. Niacin
/ D. Nitrate reductase
/ E. Urease

Q 4
The mass lesion in the patient's lung is evaluated with fiberoptic bronchoscopy with transbronchial biopsy. Sputum collected after the procedure demonstrates acid-fast bacteria with a "beaded" appearance. Giant cells found in the biopsy material would be likely to express
which of the following membrane markers?
/ A. CD4
/ B. CD8
/ C. CD14
/ D. CD16
/ E. CD19

Q 5

The principal drug recommended for treatment of this patient's disease targets which of the following molecules?
/ A. Arabinogalactan
/ B. Dihydrofolate reductase
/ C. Dihydropteroate synthetase
/ D. Mycolic acid
/ E. Peptidoglycan

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Cough Case 2 answers


A1

The correct answer is E. This patient has a positive PPD test, as indicated by an area of induration greater than or equal to 10 mm. PPD is a purified protein derivative of tuberculin, so this finding indicates that the patient has tuberculosis. The PPD reaction is an example of type IV hypersensitivity, also known as delayed-type hypersensitivity.
Type I hypersensitivity (choice A) is immediate hypersensitivity, and can be seen for example, in hay fever and atopic dermatitis.
Cytotoxic type II hypersensitivity (choice B) can be seen in autoimmune hemolytic anemia and transfusion reactions.
Noncytotoxic type II hypersensitivity (choice C) can be seen in myasthenia gravis and Graves disease.
Type III hypersensitivity (choice D) is due to immune complex deposition, and can be seen in systemic lupus erythematosus and rheumatoid arthritis.

A2

The correct answer is A. Cytotoxic T lymphocytes, T helper 1 lymphocytes, and macrophages mediate the delayed-type hypersensitivity reaction, which develops in response to viral, fungal, and intracellular bacterial antigens. Antibodies do not play a significant role in this type of response.
IgE, basophils, and mast cells (choice B) are involved in the production of type I hypersensitivity.
IgG and complement (choice C) is a mechanism of toxicity in type II cytotoxic hypersensitivity.
IgG, IgM, neutrophils, and macrophages (choice D) may be involved in types II or III hypersensitivities.
IgG, IgM, neutrophils, macrophages, and natural killers (choice E) may be involved in types II or III hypersensitivities.


A3

The correct answer is C. Mycobacterium tuberculosis is the only member of the genus Mycobacterium that is a producer of niacin.
Mycobacterium fortuitum and M. chelonae produce arylsulfatase (choice A), but M. tuberculosis does not.
Heat-stable catalase (choice B) is produced by Mycobacterium kansasii, M. avium intracellulare, and M. fortuitum, but not by M. tuberculosis.
Mycobacterium tuberculosis, M. kansasii, and M. fortuitum produce nitrate reductase (choice D), however niacin is more definitive for the identification of M. tuberculosis.

A4

The correct answer is C. CD14, the endotoxin receptor, is a standard marker for macrophages and cells of their lineage. The giant cells in a TB granuloma are histiocytes, which are modified macrophages, so they would bear macrophage cell markers.
CD4 (choice A) is a cell marker for helper T lymphocytes that would be found in the halo of lymphocytes surrounding the Langerhans giant cells, but would not be on the giant cells themselves.
CD8 (choice B) is a cell marker for cytotoxic T lymphocytes that would be present in the halo of lymphocytes surrounding the giant cells, but would not be on the giant cells themselves.
CD16 (choice D) is a cell marker for NK cells, which would not be on the giant cells in a TB granuloma.
CD19 (choice E) is a cell marker for B-lymphocytes, which are not likely to be present in a TB granuloma, a reaction mediated exclusively by cell-mediated immunity.

A5

The correct answer is D. The mainstay of therapy for tuberculosis is treatment with drugs such as isoniazid, rifampin, ethambutol, ethionamide, pyrazinamide, and streptomycin. Both isoniazid and ethionamide target the mycolic acid molecules in the mycobacterial cell wall. A single drug, usually isoniazid, can be used for chemoprophylaxis and when clinical disease is absent. Multiple drugs are usually used in other settings. Mycobacterium tuberculosis resistant to all first-line drugs is being seen with increasing frequency among AIDS patients.
Arabinogalactan (choice A) is the molecule targeted by ethambutol, which is a drug added to the anti-mycobacterial regimen only when drug-resistant strains are implicated.
Dihydrofolate reductase (choice B) is the molecule targeted by trimethoprim, which is not the principal drug recommended for treatment of tuberculosis.
Dihydropteroate synthetase (choice C) is the molecule targeted by dapsone, which is the drug of choice for Mycobacterium leprae, not M. tuberculosis.
Peptidoglycan (choice E) is the molecule targeted by the penicillins, vancomycin, and cycloserine.

Cough Case 1

A 50-year-old man consults a physician because he has developed a chronic, non-productive cough and is experiencing a reduced ability to do strenuous work. His symptoms have developed insidiously. On questioning, he states that he is a smoker and has also worked as a
contractor for all of his adult life. Physical examination is notable for the presence of repetitive end-inspiratory basal crackles and finger clubbing. A chest x-ray film shows diffusely distributed, small irregular opacities that are most prominent in the lower lung zones. Localized
areas of pleural thickening are also noted. No large masses are seen.

Q 1

The chest x-ray film is most consistent with which of the following?
/ A. Emphysema
/ B. Interstitial disease
/ C. Lobar pneumonia
/ D. Lung cancer
/ E. Pleural effusion

Q 2

The patient is sent for spirometry for further evaluation. FEV1 and FVC are both shown to be about 60% of the expected values, and the ratio of FEV1/FVC is 90%. These findings are most consistent with which of the following?
/ A. Asthma
/ B. Bronchiectasis
/ C. Chronic bronchitis
/ D. Emphysema
/ E. Restrictive lung disease


Q 3
The patient's work history is most suggestive of exposure to which of the following?
/ A. Asbestos
/ B. Beryllium
/ C. Coal
/ D. Kaolin
/ E. Silica

Q 4

In addition to predisposing for pulmonary fibrosis and bronchogenic carcinoma, this patient's disease is associated which of the following?
/ A. Basal cell carcinoma
/ B. Germ cell tumor
/ C. Hemangioma
/ D. Mesothelioma
/ E. Pleomorphic adenoma

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Cough Case 1 Answers

A1
The correct answer is B. Diffusely distributed small irregular opacities suggest the presence of interstitial lung disease.
Emphysema (choice A) would produce unusually dark lung fields.
Lobar pneumonia (choice C) would produce a "white out" of one or more lung lobes.
Lung cancer (choice D), if large, would produce a mass lesion (often involving a bronchus), or, if very small, might not be recognized on chest x-ray.
Pleural effusion (choice E) would cause a whitened area due to fluid below the lung

A2
The correct answer is E. Spirometry is commonly used to subdivide non-tumorous lung diseases into diseases that are predominately obstructive in nature and those that are predominately restrictive. The process of spirometry involves controlled breathing in and out while airflow is plotted against volume to obtain a continuous loop. FVC (forced vital capacity) is the maximum volume of air that can be forcibly and rapidly exhaled following a maximum inspiration. FEV1 (forced expiratory volume in the first second) is the volume of air expelled in the first second of a forced expiration starting from full inspiration. Restrictive lung disease usually shows a reduction in both FVC and FEV1, and the ratio of FEV1/FVC is greater than 80%. If these readings are obtained in a patient, further studies to measure lung volumes are usually performed to confirm the finding.
Asthma (choice A), bronchiectasis (choice B), chronic bronchitis (choice C), and emphysema (choice D) all tend to produce obstructive patterns, with FEV1 disproportionately decreased when compared to FVC.


A3

The correct answer is A. Working history often offers helpful clues about possible toxic exposures that may have contributed to lung disease. Asbestos was formerly a common constituent of insulating material in buildings because of both its insulating properties and its fire-resistant properties. People working on old buildings, particularly when removing the old insulation, are consequently vulnerable to high exposures unless they take care to minimize exposure with respirators. The risk to individuals living and working in old buildings is usually markedly less, since the asbestos is typically found behind walls. Individuals who work in asbestos mines (principally in Canada, South Africa, and the former USSR) may also have high exposures.
Beryllium (choice B) is used in the nuclear industry and in x-ray tubes, and was formerly used in ceramics, metallic alloys, and fluorescent lights.
Most significant coal (choice C) exposures occur in coal miners.
Kaolin (choice D) is a component of clay dust.
Silica (choice E) is found in sand and glass, and significant exposures can be seen in individuals working in environments where small particles of these materials may become aerosolized.

A4

The correct answer is D. Asbestos exposure is also linked to late (often after 20 years) development of the rare tumor, malignant mesothelioma. The amphibole forms of asbestos appear to be much more likely to induce mesothelioma than does chrysotile, and some authors have even speculated that the rare cases of mesothelioma in persons with predominant exposure to the serpentine form of asbestos may have been actually related to trace exposures to the amphibole forms. In contrast, all types of asbestos can cause pleural plaques, pulmonary fibrosis, and lung cancer. None of the other lesions listed in the choices have ties to asbestos.
Basal cell carcinoma (choice A) is a form of skin cancer.
Germ cell tumors (choice B) usually occur in testes and ovary.
Hemangioma (choice C) is a benign tumor of blood vessels.
Pleomorphic adenoma (choice E) is a salivary gland tumor.