Pitstop 1

5. A medical student is trying to explain to a classmate how to differentiate fibroblasts from other cells based on their light microscopic appearance. What characteristic(s) best describe fibroblasts? a. They reside upon a basement membrane and have a flattened appearance b. They can be identified by their fusiform/spindle shaped nucleus c. They are located on the lumenal surface of blood vessels d. They have a visibly round cytoplasm and a round nucleus

Correct Answer: B Rationale: N/A More context: A. Incorrect: do not typically reside upon a basement membrane. The description of cells residing on a basement membrane with a flattened appearance may refer to epithelial cells, particularly simple squamous epithelium, rather than fibroblasts. B. Correct: Fibroblasts are indeed characterized by a spindle or fusiform shape and have an elongated nucleus. Under the microscope, fibroblasts can typically be identified in this manner, as they often appear as irregular, spindle-shaped cells with a centrally located, elongated nucleus. This morphology allows them to be distinguished from other cell types in the connective tissue. C. Incorrect: Cells located on the luminal surface of blood vessels are endothelial cells, not fibroblasts. Endothelial cells form the inner lining of blood vessels and play crucial roles in processes like angiogenesis, blood clotting, and regulation of blood pressure, among others. D. Incorrect: Fibroblasts do not have a visibly round cytoplasm and a round nucleus. The description of cells with a round nucleus and visible cytoplasm may refer to numerous types of cells, but it does not accurately describe fibroblasts. As mentioned, fibroblasts typically exhibit a spindle shape and have an elongated nucleus.

19. Laboratory analyses reveal that your patient's infection is caused by a type of bacteria that produces a beta-lactamase. Which of the following agents, available in combination with amoxicillin, should inhibit this enzyme and make the antibiotic treatment more likely to succeed? a. Ciprofloxacin b. Clavulanate c. Metronidazole d. Penicillin

Correct Answer: B Rationale: Of the listed options, only clavulanate is a beta-lactamase inhibitor that is available in a fixed drug combination preparation with amoxicillin, an aminopenicillin, to target bacteria that produce certain beta-lactamases. Examples of such a pathogen would be methicillin-sensitive Staphylococcus aureus (MSSA) and Bacteroides fragilis. More Context: A. Incorrect: Ciprofloxacin is an antibiotic that belongs to the fluoroquinolone class and it works by inhibiting bacterial DNA gyrase. It does not inhibit beta-lactamase, thus it would not make amoxicillin more effective against bacteria that produce this enzyme. B. Correct: Clavulanate is known to be a beta-lactamase inhibitor and is frequently used in combination with amoxicillin (a beta-lactam antibiotic) to treat bacterial infections caused by beta-lactamase-producing bacteria. The clavulanate inhibits the beta-lactamase enzyme, preventing it from breaking down the amoxicillin, thereby allowing the amoxicillin to exert its antibacterial effects, which makes this option the right choice. C. Incorrect: Metronidazole is an antibiotic effective against certain parasites and anaerobic bacteria, but it does not function as a beta-lactamase inhibitor. Therefore, it would not be effective in combination with amoxicillin to overcome resistance provided by beta-lactamase production. D. Incorrect: Penicillin is also a beta-lactam antibiotic and like amoxicillin, it would be susceptible to breakdown by beta-lactamase. It is not an inhibitor of beta-lactamase and therefore, would not help in making the treatment with amoxicillin more effective against beta-lactamase-producing bacteria.

5. A patient is diagnosed with melanoma and found to have two sentinel-lymph nodes positive for cells derived from the neural crest. A positron-emission tomography (PET) scan is ordered. In preparation of the PET scan, the patient is given FDG, an analog of glucose that cannot be degraded through glycolysis. Which of the following statements explains most accurately why such a procedure is being performed on this patient? a. To detect any melanoma cells that might remain in the sentinel-lymph nodes b. To detect metastasis beyond the sentinel-lymph nodes c. To kill cancer cells through inhibition of the Warburg effect d. To kill cancer cells through positron radioactivity

Correct Answer: B Rationale: PET scan is a diagnostic imaging technique. Combined with the use of the glucose analog 2-18F-2-deoxyglucose (FDG), it can detect cell populations with relatively higher glucose uptake, which is a characteristic shared by many types of cancer including melanoma. Given that the patient has already been found to have melanoma that has spread out of its primary site and invaded the first set of lymph nodes proximal to the primary site (following lymph circulation), FDG-PET scan is now being ordered to attempt to detect any evidence of distant metastasis in other tissues. The FDG is administered as a tracer dose, and, as such, has no pharmacological effects. More context: A. Incorrect: While PET scans do visualize areas of increased glucose metabolism, which is typical of cancer cells, and thus, could potentially detect melanoma cells in lymph nodes, the sentinel nodes have already been identified as positive for melanoma cells. The main purpose here would not be to check again in the same nodes. B. Correct: PET scans with FDG are widely used in oncology due to the high glucose metabolism of cancer cells. The PET scan will identify areas of high FDG uptake, which can indicate the presence of metastatic melanoma cells in areas distant from the already-identified sentinel nodes, thus assisting in staging the cancer and determining further management. C. Incorrect: FDG is indeed an analog of glucose and is taken up by cells, but it doesn't have a therapeutic role in inhibiting glycolysis or killing cancer cells by inhibiting the Warburg effect. The Warburg effect relates to the altered metabolism of cancer cells to preferentially utilize glycolysis even in the presence of oxygen, but the FDG in PET scans is not administered at doses that would impact this process in a therapeutically relevant manner. D. Incorrect: The FDG utilized in PET scans does emit positrons, which are detected by the PET scanner to create the images. However, the radiation from FDG in PET scanning is not utilized with the intent or dosage to kill cancer cells; its primary role is in imaging.

22. A specimen from a patient grows bacteria that belong to the family Enterobacterales. Which of the following statements best describes all bacteria of this family? a. None of them can ferment glucose b. They contain and an outer and inner cell membrane c. They contain a thick peptidoglycan layer d. They express the mecA gene to resist certain classes of antibiotics

Correct Answer: B Rationale: The Enterobacterales are a family of gram-negative rods, housing important genera such as Proteus, E. coli and Klebsiella. All gram-negative bacteria contain an inner and outer cell membrane, with a thin (not thick) peptidoglycan cell wall sandwiched in between. All members of the Enterobacterales family, except Proteus, ferment glucose. Finally, mecA is a gene acquired by Staphylococcus aureus, which encodes PBP2A, an altered penicillin-binding protein (PBP) that confers methicillin-resistance; mecA is not a mechanism of resistance among Enterobacterales. More context: ● mecA gene: Staph--MRSA A. Incorrect: Most members of the Enterobacterales family are capable of fermenting glucose. Enterobacterales include important groups of bacteria like Escherichia coli, Klebsiella, and Salmonella, which can ferment glucose as part of their metabolic processes. B. Correct: All members of the Enterobacterales family are Gram-negative bacteria, which means they have an outer and an inner cell membrane, with a periplasmic space in between that contains a thin peptidoglycan layer. C. Incorrect: Gram-negative bacteria, including those in the Enterobacterales family, do not have a thick peptidoglycan layer; rather, their cell wall structure is characterized by the outer membrane, which contains lipopolysaccharides, and the thin peptidoglycan layer in the periplasmic space. D. Incorrect: The mecA gene, which confers resistance to certain beta-lactam antibiotics by encoding an altered penicillin-binding protein, is associated with Staphylococcus aureus (a Gram-positive coccus) and not with Gram-negative rods in the Enterobacterales family.

4. You biopsy a lesion that contains the cells marked by the arrows in the image. Which of the following is the most likely primary pathological process? a. Acute inflammation b. Chronic Inflammation c. Neoplasm d. Wound healing

Correct Answer: B Rationale: The cells highlighted are plasma cells. Note the perinuclear hof, eccentric nucleus, and the clockface appearance of the chromatin. Plasma cells can be seen in chronic inflammatory responses. More Context: A. Incorrect: Plasma cells are not typically associated with acute inflammation. In acute inflammation, you would expect to find neutrophils as the predominant immune cells, along with macrophages. Neutrophils are the first responders to acute infection or injury. The neutrophils are diffused (more spread out) throughout the inflamed tissue. B. Correct: Plasma cells are commonly associated with chronic inflammation. In chronic inflammation, immune cells such as lymphocytes (e.g. T cells- CD4/CD8 and B cells), macrophages, and plasma cells are present. Plasma cells produce antibodies and play a role in the immune response against long-lasting infections or autoimmune conditions. There are clumps of lymphocytes that are in one area of the tissue. C. Incorrect: Neoplasms (tumors) can involve various cell types depending on the type of cancer. However, the presence of plasma cells alone is not a typical feature of neoplasms. In neoplasms, you might find abnormal or rapidly dividing cells specific to the tissue involved. D. Incorrect: Wound healing involves various stages, including inflammation, proliferation, and tissue remodeling. In the inflammatory phase, you would typically find neutrophils and macrophages responding to clear debris and initiate the healing process. Plasma cells are not the primary cells associated with wound healing unless there is an underlying infection or persistent inflammation in the wound.

11. Therapeutic monoclonal antibodies (mAbs) are administered parenterally by intravenous, subcutaneous, or intramuscular routes. Which of the following is most likely to represent an advantage of subcutaneous or intramuscular administration over intravenous administration? A. Better ability to inject large volumes B. Lower rates of adverse events C. More rapid rate of onset of action D. Relatively higher bioavailability

Correct Answer: B Rationale: The intravenous route is the most common for mAbs to date and is advantageous with respect to the speed of systemic delivery, complete bioavailability, and ability to deliver high volumes. It has shortcomings, however, related to convenience, cost, and a potential for triggering infusion reactions. Subcutaneous and intramuscular delivery have lower bioavailability (~25-95%) and delayed rates of onset of action due to their slow transit from interstitial space through lymphatic vessels before reaching systemic circulation (hours to days) but provide the advantages of self administration in the home setting and lower rates of adverse events related to drug infusion. More context: A. Incorrect: Intravenous (IV) administration, which means giving medicine directly into the bloodstream through a vein, allows doctors to give larger amounts of medicine at one time compared to other methods. Subcutaneous (SC) and intramuscular (IM) methods, which involve injecting medicine into fat or muscle tissue, can't handle as much volume because they use tissues, not veins. B. Correct: When medicines are given via SC or IM, which involve injections into the fat or muscle, there are usually fewer negative side effects (like bad reactions while the medicine is being given) compared to IV. The slower and more gradual entry of the drug into the bloodstream from muscle or fat tissues might help in avoiding some negative reactions that can occur when medicines quickly enter directly into the blood via IV. C. Incorrect: Medicines given directly into the blood (IV) work faster than medicines injected into fat or muscle tissue (SC or IM). This is because IV medicines don't have to be absorbed into the bloodstream from another part of the body - they're already there. So, the statement that SC or IM work faster is not accurate. D. Incorrect: Bioavailability means how much of the medicine actually gets into the bloodstream to work. Giving medicine directly into the blood (IV) means all of it is available to work immediately. When given into the fat or muscle (SC or IM), the medicine takes time to move from the tissue into the blood, so not all of it is available to work immediately and sometimes, som

11. Which of the following pairs of bacteria species can be distinguished from each other in the clinical microbiology lab using the coagulase test, which assess the ability of bacteria to cause plasma to clot? a. Escherichia coli and Proteus mirabilis b. Staphylococcus aureus and Staphylococcus epidermidis c. Streptococcus pyogenes and Enterococcus faecalis d. Streptococcus pyogenes and Staphylococcus aureus

Correct Answer: B Rationale: The production of coagulase differentiates Staphylococcus aureus (coagulase positive) from Staphylococcus epidermidis (coagulase negative). More Context: A. Incorrect: Both E. coli and Proteus mirabilis are Gram-negative rods, and the coagulase test, which is used to differentiate Staphylococcus species, is not typically used to distinguish between these two bacteria. B. Correct: The coagulase test is used to differentiate between Staphylococcus species. Staphylococcus aureus is coagulase-positive, meaning it can clot plasma, while Staphylococcus epidermidis is coagulase-negative. Thus, this test can distinguish between these two species. C. Incorrect: The coagulase test is not typically used to differentiate between these two gram positive Streptococcus and Enterococcus species as neither of these is known to produce coagulase. Differentiating these organisms might instead involve tests based on their hemolytic properties on blood agar, among other characteristics. D. Incorrect: Although Staphylococcus aureus (coagulase-positive) can be differentiated from other bacteria using the coagulase test, Streptococcus pyogenes does not produce coagulase and is typically distinguished from staphylococci using other methods, such as the catalase test (streptococci are catalase-negative, while staphylococci are catalase-positive).

10. An infant presents with skin findings as shown in the picture. Which of the following best explains the underlying mechanism for this skin change? a. Enterotoxin destroying dermis and promoting bacterial invasion b. Production of a protease that cleaves desmoglein c. Teichoic acid interacting with toll-like receptor 2 d. TSST-1 acting as a superantigen and causing cytokine release

Correct Answer: B Rationale: The skin findings shown in the image are most consistent with Staphylococcal scalded skin syndrome (SSSS) in an infant, not toxic shock. These patients do need to be hospitalized and are treated like "burn patients" but they are not necessarily in shock. The pathogenesis is the production of exfoliative exotoxin [protease] that cleaves desmoglein [in desmosomes] and leads to peeling skin. Teichoic acid makes Staph 'sticky'. TSST-1 does act like a superantigen in toxic shock syndrome. Enterotoxin is the heat-stable toxin that causes Staphylococcal food poisoning. More Context: a. Incorrect: Staphylococcal Scalded Skin Syndrome (SSSS) primarily affects the epidermis, not the dermis. It does not involve the destruction of the dermis or promote bacterial invasion into the dermis. b. Correct: SSSS is caused by exfoliative toxins produced by Staphylococcus aureus. These toxins specifically target and cleave desmoglein, a protein that plays a crucial role in the adhesion of skin cells in the epidermis. The cleavage of desmoglein leads to the separation of the epidermis from the underlying dermis, resulting in blistering and skin peeling. c. Incorrect: While Staphylococcus aureus contains cell wall components like teichoic acids that can interact with toll-like receptors, this mechanism is not the primary cause of the skin changes in SSSS. d. Incorrect: TSST-1 (Toxic Shock Syndrome Toxin-1) is associated with toxic shock syndrome and cytokine release but is not the primary toxin responsible for the skin changes seen in SSSS. The primary mechanism in SSSS is the cleavage of desmoglein by exfoliative toxins.

18. A 62-year-old male with emphysema is treated with prednisone and levofloxacin for an exacerbation of his chronic pulmonary disease. During the course of treatment, he presents with a thick white coating on his tongue and pharynx. Which of the following is the most likely pathogen cultured from a swab of his throat? A. Aspergillus fumigatus B. Candida albicans C. Staphylococcus aureus D. Streptococcus pyogenes

Correct Answer: B Rationale: This is an example of thrush, which is caused by the overgrowth of Candida albicans. Both antibiotics and steroids can predispose individuals to developing thrush. More context: A. Incorrect: This fungus can cause infection but it's not known for causing a white coating on the tongue and throat. So, this is not the bug we're looking for. B. Correct: Yes, this is the one! *Candida albicans* is a yeast that can grow too much when a person takes antibiotics (like levofloxacin) and steroids (like prednisone). The overgrowth in the mouth is called "thrush" and it shows as a white coating, which is exactly what happened to the man. C. Incorrect: This bacterium can cause infections but it doesn't cause a white coating in the mouth. So it's not the right answer. D. Incorrect: This one can cause throat infections but it doesn't create a white coating like what the man has. So this isn't our bug.

17. A 27-year-old female presents to the Emergency Department for evaluation of severe abdominal pain that has been worsening over 48 hours. She has trouble localizing her pain. She is also experiencing numbness in her hands. Her symptoms started shortly after being started on phenytoin (a medication to prevent seizures) for treatment of a new-onset seizure disorder. She works as a lawyer and has been facing several stressful deadlines. She has not had similar symptoms in the past. Her vitals are: temperature 37.1ºC, heart rate 107 beats per minute, and blood pressure 118/71 mm Hg. Physical exam shows decreased strength of the bilateral shoulders and biceps. The abdominal exam is normal. A complete blood count and complete metabolic panel are within normal limits. An additional test reveals high levels of urine porphobilinogen. A CT scan of the abdomen is normal. Based on this information, a medication with which of the following mechanisms of action should be used to treat this patient? a. Increase in hemoglobin F production b. Negative feedback on the heme synthesis pathway c. Stimulation of platelet production in the bone marrow d. Suppression of the immune system

Correct Answer: B Rationale: This patient has a classic history for acute intermittent porphyria (AIP). Patients typically present for an acute episode and may, or may not, have had prior episodes. Typical symptoms include: severe, poorly localized abdominal pain, anxiety, and dysfunction of peripheral nerves (peripheral neuropathy) leading to symptoms including numbness, tingling, and weakness. Urine porphobilinogen (PBG) is elevated in AIP. AIP can be triggered by certain medications (in particular anti-seizure medications including barbiturates and phenytoin, which you will learn about later in SFM; notice that this fact was not needed to answer this question correctly but provides you with a "first pass" of information that will want to know for USMLE step 1). AIP can also be triggered by stress, alcohol intake, and prolonged fasting. Treatment of AIP is with hemin, which provides negative feedback to the heme synthesis pathway and thereby decreases the buildup of the toxic intermediates that cause the symptoms of AIP. "Increase in hemoglobin F production" describes the mechanism of hydroxyurea, which is used to treat sickle cell anemia. "Stimulation of platelet production in the bone marrow" describes thrombopoietin, which can be used to treat certain causes of thrombocytopenia; however, the complete blood count (CBC), which should include platelet count, is normal in this patient. "Suppression of the immune system" could refer to agents such as corticosteroids, which can be used to treat autoimmune conditions such immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (although low hemoglobin level or platelet count would be expected with these conditions). AIP is not an autoimmune condition; rather, it is a genetic disease caused by pathogenic variants in a gene encoding an enzyme of the pathway for heme synthesis. More Context: A. Incorrect: This option is incorrect because increasing hemoglobin F production does not directly address the underlying metabolic issue of AIP, which involves accumulation of porphyrin precursors (such as porphobilinogen) due to a defect in the heme synthesis pathway. Hemoglobin F (fetal hemoglobin) increasing medications are more relevant to conditions li

18. The sister of one of the parents of a 3-year-old female recently diagnosed with cystic fibrosis (CF) is pregnant and, once she hears the news of the diagnosis of her niece, asks for a referral to a genetic counselor because of concerns that her unborn baby might end up suffering from the same disease. The genetic counselor learns about the family history of the mother-to-be, with no family member other than the patient recently diagnosed with CF. The side of the family of the father-to-be has no history of CF or CF-related disease. The father-to-be is from a family that for centuries lived in what is now the country of Denmark, where the incidence of CF is about 1 every 2000 births. Based on the information available to the genetic counselor, which of the following is the best estimate of the risk of CF in this unborn baby? a. <0.01% b. ~0.1% c. ~0.5% d. ~5%

Correct Answer: C Rationale: Assuming that the pathogenic variants causing CF in the newly diagnosed patient have been inherited for at least two generations (as opposed to having recently arisen de novo), the probability of the mother-to-be, i.e., the sibling of an obligate carrier, being a carrier is 1/2. As for the father-to-be, based on the information provided and assuming that the conditions of Hardy-Weinberg are met, one may estimate the probability of him being a carrier as ~2q, or ~2/√2000, or ~1/22. Accordingly, the risk of CF in the unborn baby would be: 1/2 x 1/2 x ~1/22 x 1/2, or ~1/176 (~0.57%). More Context: 1. Probability of the mother-to-be being a carrier: Her sibling (the parent of the CF patient) is an obligate carrier, so she has a 50% (or 1/2) chance of also being a carrier. 2. Probability of the father-to-be being a carrier: With CF (q2) incidence of 1 in 2000 births in Denmark, we are looking for q by itself so the square root of 1/2000 is 0.005. =2pq=2(1)(.022)=0.044 3. Probability of the child inheriting the disease: If both parents are carriers, each has a ½ chanc of giving the allele to the kid. So ½ from mom and ½ from dad multiplythat and you get ¼ (25%) chance that their child will have CF. Risk of CF= (Probability mother is a carrier) × (Probability father is a carrier) × (Probability child inherits CF) Risk of CF= (1/2) x (.044) x (1/4)= 0.0055 Make it a percentage. 0.0055 x 100%= 0.55%

13. Two siblings in their early forties report to their corresponding primary care physician similar symptoms of bloating and loose stools lasting for nearly a year. The older sibling reports that the symptoms are minimal as long as milk and other dairy products are avoided in the diet, while the younger sibling reports experiencing the symptoms despite rarely consuming milk and related products but, on the other hand, having a 'sweet tooth' that often is hard to control. Notwithstanding the reported differences in diet, which of the following general mechanisms is the most likely explanation for the gastrointestinal symptoms in both siblings? a. Constitutively activated chloride channel b. Enteric viral infection c. Impaired carbohydrate absorption d. Impaired export of chylomicrons

Correct Answer: C Rationale: Based on the available information, the older sibling may be experiencing poor tolerance to lactose, due to low expression levels of the digestive enzyme lactase, while the younger sibling may be ingesting more fructose than what the intestinal epithelial cells can absorb via the saturable diffusion facilitator, GLUT5. In both scenarios, the unabsorbed saccharides (i.e., the undigested lactose or the excess fructose) would retain fluid inside the lumen of the gut (essentially acting as osmotic laxatives) and, upon reaching the colon, be metabolized by bacteria to generate gas. More Context: A. Incorrect: A constitutively activated chloride channel might cause watery diarrhea due to increased chloride secretion into the lumen of the intestine, which would draw water into the lumen osmotically. However, the variation in symptoms between the two siblings based on different dietary habits (dairy avoidance and high sugar intake) doesn't align with a mechanism involving chloride channel activity, which would likely be unresponsive to dietary changes. B. Incorrect: A chronic enteric viral infection lasting for nearly a year would be an unusual duration for viral-induced gastrointestinal symptoms and doesn't align well with the symptom chronicity reported by the siblings. Furthermore, the siblings have symptoms that are modulated by different dietary patterns, which is not characteristic of viral infections that typically cause transient, not chronic, and usually not diet-dependent gastrointestinal symptoms. C. Correct: The older sibling's symptom improvement with dairy avoidance suggests lactose intolerance, where lactose is not adequately digested due to low lactase enzyme activity, leading to osmotic diarrhea and gas production when colonic bacteria ferment the undigested lactose. Meanwhile, the younger sibling's high sugar intake, particularly if high in fructose, could overwhelm GLUT5 transporters in the intestines, leading to malabsorption of fructose, similar osmotic effects, and fermentation. Thus, both scenarios involve impaired carbohydrate absorption, albeit of different types of carbohydrates, and therefore, this mechanism best explains the gastrointestinal symptoms ex

21. A patient reports fever and diarrhea for 5 days. He is found to have a pathogen that causes disease via invasion into the intestinal mucosa. Which of the following pathogens is most likely to be responsible for his symptoms? a. Clostridioides difficile b. Klebsiella Pneumoniae c. Salmonella enterica d. Vibrio cholerae

Correct Answer: C Rationale: Of the listed options, the only invasive pathogen is Salmonella enterica, a motile, gram-negative bacillus found commonly in poultry and egg-products that enters intestinal epithelium, causing bacterial gastroenteritis. Vibrio cholerae and C. difficile cause diarrhea via secreted toxins - cholera toxin and Clostridiodes toxins, respectively, rather than invading GI epithelial cells. Klebsiella pneumoniae is a commensal and does not cause diarrhea. More Context: A. Incorrect: C. difficile indeed causes diarrhea, but it doesn't invade the intestinal mucosa. Rather, it releases Clostridiodes toxins (TcdA and TcdB) that damage the lining of the colon, which is a different mechanism of inducing disease compared to invasion into the intestinal mucosa. B. Incorrect: While K. pneumoniae can be associated with various infections, it is not typically a cause of infectious diarrhea and it doesn't invade the intestinal mucosa to cause disease. It's more commonly associated with pneumonia and other hospital-acquired infections. C. Correct: S. enterica invades the intestinal mucosa and can thereby cause symptoms like fever and diarrhea. It is known for causing bacterial gastroenteritis by invading and inflaming the intestinal wall, aligning with the patient's symptoms and disease mechanism, making it the most likely pathogen in this scenario. D. Incorrect: V. cholerae does cause severe, often watery diarrhea, but it does so through a toxin-mediated mechanism, not by invading the intestinal mucosa. The cholera toxin it produces leads to secretion of water and electrolytes into the intestinal lumen, but the bacteria itself does not invade the intestinal cells.

13. Following incision and drainage, which of the following antimicrobials is most appropriate for the treatment of a large abscess caused by methicillin-sensitive Staphylococcus aureus? a. Amoxicillin (without clavulanate) b. Aztreonam c. Cefazolin d. Penicillin

Correct Answer: C Rationale: Amoxicillin will not work without a beta-lactamase inhibitor. Aztreonam covers gram-negative pathogens only. Penicillin is not effective against Staphylococcus aureus due to the presence of beta-lactamase. More Context: A. Incorrect: Amoxicillin without clavulanate is not the best option for treating an abscess caused by Staphylococcus aureus because S. aureus often produces a beta-lactamase, which could inactivate amoxicillin. B. Incorrect: Aztreonam is not appropriate for treating infections caused by Staphylococcus aureus as it primarily covers gram-negative pathogens and has no activity against gram-positive bacteria like Staphylococcus aureus. C. Correct: Cefazolin is a suitable choice for treating an abscess caused by methicillin-sensitive Staphylococcus aureus (MSSA) due to its beta-lactamase stability and efficacy against MSSA. D. Incorrect: Penicillin is generally not recommended for treating Staphylococcus aureus infections due to the high prevalence of beta-lactamase-producing strains, which would inactivate penicillin.

12. A 29-year-old female attends the HIV clinic at UCLA. She has recently been diagnosed HIV positive and is ready to start antiretroviral therapy. Which of the following regimens is the most appropriate for her to start? A. An integrase inhibitor and two entry inhibitors B. An integrase inhibitor and two non-nucleoside reverse transcriptase inhibitors C. An integrase inhibitor and two nucleoside reverse transcriptase inhibitors D. An integrase inhibitor and two protease inhibitors

Correct Answer: C Rationale: An integrase inhibitor OR a boosted protease inhibitor, plus two nucleoside reverse transcriptase inhibitors, is the recommended first-line treatment for HIV. More context: A: Incorrect. This combo isn't the first go-to for starting HIV treatment because it isn't as effective and safe as other options. B: Incorrect. This mix isn't usually the first pick because it can lead to issues like drug resistance and side effects, which we want to avoid when starting treatment. C: Correct. This combination is typically chosen first for HIV treatment because it works well, is safe, and has fewer side effects, making it a good starting point. D: Incorrect. This pairing isn't usually used first because it can cause more side effects and is harder to manage, especially when just starting treatment. HIV: antiretroviral therapy ● Need at least 2 Targets: Reverse Transcriptase ○ 2 NRTI (nucleoside/nucleotide) "backbone" ■ NRTI: competitive inhibition (chain termination) ○ + 1 "Anchor drug" options: ■ Integrase transfer inhibitor: inhibits integrase into host DNA ■ Boosted Protease inhibitor ■ NNRTI (Non-nucleoside RT): noncompetitive inhibition (change conformation) HIV Antiretroviral Drug Classes we should know the mechanisms: 1. NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors) - Function: Bind to the active site of the reverse transcriptase enzyme. - Action: Inhibit viral replication by causing chain termination during the DNA synthesis phase. - Risks: Resistance may develop with incorrect use. 2. NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) - Function: Bind non-competitively to the reverse transcriptase enzyme. - Action: Alter the enzyme's conformation, making it non-functional in reverse transcription. 3. PIs (Protease Inhibitors) - Function: Inhibit the enzyme protease. - Action: Prevent the maturation of the virus by inhibiting the cleavage of proteins during viral assembly, notably affecting the creation of the viral capsid. 4. INSTIs (Integrase Strand Transfer Inhibitors) - Function: Block the enzyme integrase. - Action: Halt the integration of viral cDNA into the host cell's DNA, interrupting the viral lifecycle in the ho

1. Detailed evaluation of a patient with immune deficiency leads to the diagnosis of chronic granulomatous disease (CGD). Which of the following physiological functions is most likely impaired in this patient? a. Catabolism of hydrogen peroxide by glutathione peroxidase b. Production of NADPH by the pentose phosphate pathway c. Production of oxygen superoxide in phagosomes of neutrophils and macrophages d. Synthesis of deoxy-adenosine in B and T lymphocytes

Correct Answer: C Rationale: CGD comprises a group of genetic disorders caused by mutations in subunits of the NADPH oxidase complex expressed in neutrophils and macrophages. Upon phagocytosis, the full complex is assembled on the phagosome membrane and generates oxygen superoxide from molecular oxygen, using NADPH as a cofactor. Defective NADPH oxidase activity in these cells impairs their ability to kill microorganisms in phagosomes. More context: A. Incorrect: Catabolism of hydrogen peroxide by glutathione peroxidase is not the primary defect in chronic granulomatous disease (CGD). Glutathione peroxidase is an enzyme that reduces hydrogen peroxide and helps to mitigate oxidative stress within the cell, but the fundamental issue in CGD pertains to the inability to generate superoxide in phagosomes to kill ingested microorganisms. The catabolism of hydrogen peroxide is what is defective in G6PD deficiency (common; test before anti-malaria drugs) B. Incorrect: Production of NADPH by the pentose phosphate pathway is not directly impaired in CGD. While NADPH is crucial for the activity of the NADPH oxidase complex (and thereby indirectly involved in the disease mechanism), the primary defect in CGD is not in the production of NADPH but in the generation of superoxide within phagosomes of immune cells. C. Correct: Chronic granulomatous disease is characterized by the impaired production of oxygen superoxide in the phagosomes of neutrophils and macrophages due to a deficiency in the NADPH oxidase complex. The superoxide is necessary to create a bactericidal oxidative burst that is essential for effective killing of ingested microorganisms. A deficiency in this mechanism leads to the immune deficiency and increased susceptibility to certain bacterial and fungal infections seen in CGD. D. Incorrect: Synthesis of deoxy-adenosine in B and T lymphocytes is not the primary dysfunction in CGD. Issues with adenosine synthesis pertain to a different type of immune deficiency called adenosine deaminase deficiency, which is a form of severe combined immunodeficiency (SCID), not CGD. The hallmark of CGD is a defect in microbial killing due to impaired superoxide production in phagocytic cells, as explained above in

2. A patient is diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency following an episode of acute hemolytic anemia apparently triggered by taking an anti-malaria drug. Which of the following statements best explains how such a widely used drug may cause destruction of red blood cells (RBCs) in G6PD-deficient individuals? a. It activates the Na+/K+-ATPase, for which G6PD-deficient RBCs cannot supply enough ATP due to impaired glycolysis. b. It kills RBCs infected with Plasmodium falciparum, to which G6PD-deficient RBCs are more susceptible than normal RBCs. c. It leads to production of hydrogen peroxide, which G6PD-deficient RBCs fail to eliminate due to low NADPH levels d. It prevents nucleotide synthesis de novo, which in G6PD-deficient cells is partially impaired

Correct Answer: C Rationale: Certain anti-malaria medications elicit the production of reactive oxygen species, including hydrogen peroxide. RBCs use an enzymatic system for elimination of hydrogen peroxide that relies on glutathione in reduced form. G6PD is a key enzyme of the only pathway that mature RBCs have to generate NADPH, which is required by the above-mentioned enzymatic system to regenerate glutathione in reduced form. More context: A. Incorrect: G6PD deficiency primarily affects the pentose phosphate pathway, not glycolysis. It doesn't directly impact ATP production, so activating Na+/K+-ATPase is not the issue. B. Incorrect: The hemolytic anemia seen in G6PD deficiency when using certain anti-malaria drugs is related to an inability to deal with oxidative stress created by the drug, not increased susceptibility to infection of the RBCs. C. Correct: Anti-malaria drugs can induce oxidative stress in RBCs. In individuals with G6PD deficiency, the cells are unable to adequately manage this stress due to reduced availability of NADPH, which is crucial for maintaining glutathione in a reduced state to neutralize reactive oxygen species such as hydrogen peroxide. Consequently, hydrogen peroxide and other reactive oxygen species accumulate and damage the RBCs, leading to hemolysis. D. This statement is not directly related to the mechanism of hemolysis caused by the anti-malaria drug. G6PD deficiency primarily affects the pentose phosphate pathway, not nucleotide synthesis de novo.

3. Which of the following describes the term dysplasia most accurately? a. Activation of proteins that promote apoptosis b. A neoplasm that has invaded nearby normal tissue c. Disordered growth that can lead to a loss in the uniformity and tissue architecture d. Immune response necessary to clear an infection e. The growth of new blood vessels

Correct Answer: C Rationale: Dysplasia is defined as a disorderly but non-neoplastic proliferation. It does not necessarily progress to cancer, thus it is not a 'neoplasm'. It does not include growth of new blood vessels. It is a loss in the uniformity of individual cells and their architectural characteristics. More Context: A. Incorrect: Dysplasia refers to abnormal cell growth and development, which could potentially lead to a precancerous condition. It does NOT directly involve the activation of proteins that promote apoptosis (programmed cell death). B. Incorrect: Dysplasia does NOT refer to the invasiveness of a neoplasm. Rather, it signifies abnormal development and growth of cells. Invasiveness into nearby tissues is more representative of malignant neoplasms and not of dysplastic changes per se. C. Correct: Dysplasia involves abnormal cell development, which results in cells that vary in size and shape, leading to a loss of uniformity and architecture in the tissue. These cells may also not function as expected and the condition, depending on its severity and persistence, might develop into a cancerous lesion. D. Incorrect: Dysplasia does not directly pertain to immune responses or infection clearance. It is characterized by abnormal, non-uniform cell growth, which is not an immune response. E. Incorrect: The growth of new blood vessels, known as angiogenesis, is not what dysplasia describes. Dysplasia refers to abnormal cellular development and growth which may lead to precancerous conditions, while angiogenesis is a process that can support the growth of tumors by supplying them with nutrients through new blood vessels, but it's not related to the cellular abnormalities seen in dysplasia.

16. Which of the following agents is most effective to counteract the anticoagulant effect of heparin in patients before surgery, after renal dialysis, after open-heart surgery, if excessive bleeding occurs, or if an overdose has inadvertently been given? a. Andexanet alfa b. Idarucizumab c. Protamine d. Warfarin

Correct Answer: C Rationale: Heparin, which belongs to the family of glycosaminoglycans (GAGs), is a linear sulfated polysaccharide and consists of repeating disaccharide subunits of α-1,4 linked uronic acid and D-glucosamine. This polyanion is widely used as an intravenous anticoagulant due to its ability to accelerate the rate at which antithrombin (AT) inhibits serine proteases within the blood coagulation cascade, most notably factor Xa and thrombin. Unfractionated heparin as a strongly anionic anticoagulant forms a salt aggregate when exposed to the positive cationic arginine peptide of protamine. The salt aggregate that forms is inactive and has no anticoagulant properties. Protamine has a rapid onset of action, neutralizes unfractionated heparin within 5 minutes, and has a relatively short half-life of approximately 10 min. Protamine is inactive toward fondaparinux. Andexanet alfa is a recombinant modified human factor Xa (FXa) protein indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. It binds to the Xa inhibitor-drug, thus allowing prothrombin → thrombin conversion by Xa. Idarucizumab is a humanized monoclonal antibody fragment as a specific reversal agent for dabigatran with no impact on the effect of other anticoagulant or antithrombotic therapies. More Context: A. Incorrect: Andexanet alfa is a specific reversal agent for direct factor Xa inhibitors and does not reverse the anticoagulant effect of heparin. It would not be effective in this context. B. Incorrect: Idarucizumab is a monoclonal antibody fragment that is used as a reversal agent for dabigatran, a direct thrombin inhibitor. It does not counteract the anticoagulant effects of heparin and is therefore not the @ Correct Answer. C. Correct: Protamine is a drug that is widely recognized as an antidote to heparin. It binds to heparin, forming a stable complex and thereby neutralizing its anticoagulant effect. It is commonly used in situations where rapid reversal of heparin's anticoagulant effect is required, such as before surgery, after renal dialysis, after open-heart surgery, or in cases of excessive bleeding or overdose of hepa

20. Laboratory testing reveals abnormally low plasma folate levels in a patient of yours. Which of the following combinations of results from subsequently measuring methylmalonic acid (MMA) and homocysteine in serum from the same patient would be most consistent with folate deficiency? a. Elevated MMA and elevated homocysteine b. Low MMA and elevated homocysteine c. Normal-range MMA and elevated homocysteine d. Normal-range MMA and low homocysteine

Correct Answer: C Rationale: Homocysteine is methylated to create methionine in a reaction that requires methyl folate (methyl donor) and vitamin B12. Deficiencies of either vitamin will result in elevated homocysteine serum levels. Elevated MMA levels result from vitamin B12 deficiency only. More Context: A) Elevated MMA and elevated homocysteine - Incorrect: Elevated methylmalonic acid (MMA) and homocysteine levels are more indicative of a vitamin B12 (cobalamin) deficiency rather than a folate deficiency. Both of these markers are elevated in vitamin B12 deficiency because both vitamin B12 and folate are required for the conversion of homocysteine to methionine and the breakdown of MMA. Folate deficiency primarily results in elevated homocysteine levels with normal MMA levels. B) Low MMA and elevated homocysteine - Incorrect: Low MMA levels are not typically associated with folate deficiency. Elevated homocysteine levels are consistent with folate deficiency, but low MMA is not a characteristic finding in folate deficiency. Low MMA is more commonly seen in vitamin B12 deficiency. C) Normal-range MMA and elevated homocysteine - Correct: This combination of normal-range MMA and elevated homocysteine levels is most consistent with folate deficiency. Folate is necessary for the conversion of homocysteine to methionine, and when folate levels are low, homocysteine levels tend to rise. MMA levels remain within the normal range in folate deficiency because MMA is primarily influenced by vitamin B12 status. D) Normal-range MMA and low homocysteine - Incorrect: Normal-range MMA and low homocysteine levels are not typically seen in either folate or vitamin B12 deficiency. This combination is not consistent with either of these nutrient deficiencies.

9. A 7-year-old child presents with the skin findings shown below. Which of the following is the best treatment for this condition? a. A corticosteroid cream b. An anti-herpetic drug c. An anti-staphylococcal drug d. Exposure to UV light

Correct Answer: C Rationale: Impetigo is best treated with an anti-staphylococcal drug. Herpes simplex virus (HSV) or Zoster would be treated with acyclovir or related drugs. Corticosteroids are used for purely inflammatory conditions (not caused by infection). UV light can contribute to HSV reactivation and is used in treatment of psoriasis. More context: A. Incorrect: Corticosteroid creams are generally used to reduce inflammation and are not typically used as a first-line treatment for bacterial infections like impetigo. They may be used in certain skin conditions like eczema or psoriasis but would not be the best treatment for a bacterial skin infection. B. Incorrect: Anti-herpetic drugs are utilized for viral infections caused by the herpes simplex virus. Since impetigo is a bacterial infection, commonly caused by Staphylococcus aureus, an anti-herpetic drug would not be appropriate for treatment. C. Correct: Impetigo is commonly caused by the bacteria Staphylococcus aureus, and thus, an anti-staphylococcal drug would be the most appropriate treatment to target and eliminate the underlying cause of the condition. D. Incorrect: UV light therapy might be utilized for conditions like psoriasis but is not a standard treatment for bacterial infections like impetigo. Additionally, exposing a young child's skin to UV light can have detrimental effects and is typically avoided when possible, especially as a treatment method.

18. A patient develops septicemia in the setting of a urinary tract infection due to E. coli. Which one of the following is a component of the human innate immune system that recognizes specific bacterial patterns leading to cytokine secretion? a. Lipopolysaccharides b. Neutrophil extracellular trap (NETs) c. Toll-like receptors (TLRs) d. Tumor necrosis factor (TNF)

Correct Answer: C Rationale: Innate immunity to pathogens relies on pattern recognition receptors (PRRs), including toll-like receptors (TLRs), which allow immune cells to respond rapidly to a wide range of pathogens that share common structures known as pathogen-associated molecular patterns (PAMPs). Lipopolysaccharides are gram-negative bacterial cell wall component that are an example of these PAMPs. Tumor necrosis factor (TNF) is an inflammatory cytokine released during the early response to infection. Neutrophil extracellular traps (NETs) are net-like structures released by activated neutrophils. More Context: A. Incorrect: Lipopolysaccharides (LPS) are components of the bacterial cell wall, particularly in Gram-negative bacteria like E. coli. They are recognized by the innate immune system, but they are not a component of the human innate immune system. Instead, they are recognized by various pattern recognition receptors (PRRs) on immune cells, such as Toll-like receptors (TLRs). B. Incorrect: Neutrophil extracellular traps (NETs) are structures released by neutrophils to capture and kill pathogens, but they do not play a role in recognizing specific bacterial patterns leading to cytokine secretion. NETs are more involved in the direct trapping and killing of bacteria. C. Correct: Toll-like receptors (TLRs) are a critical component of the human innate immune system that recognizes specific bacterial patterns, such as bacterial cell wall components like lipopolysaccharides (LPS). When TLRs recognize these patterns, they trigger a signaling cascade that leads to the secretion of cytokines and other immune responses. TLRs play a central role in the innate immune response to infections. D. Incorrect: Tumor necrosis factor (TNF) is a cytokine produced by immune cells in response to infection, but it is not a component of the innate immune system that recognizes specific bacterial patterns. TNF is involved in the inflammatory response and can be induced by the activation of pattern recognition receptors like Toll-like receptors (TLRs).

13. Which of the following potential causes of anemia is least likely to involve impaired synthesis of nucleotides? a. Chemotherapy with drugs inhibiting folate metabolism b. Hereditary orotic aciduria c. Iron deficiency d. Vitamin B12 deficiency

Correct Answer: C Rationale: Iron deficiency is expected to impair the synthesis of hemoglobin but not of DNA. All other options are expected to impair de novo synthesis of nucleotides (in the case of hereditary orotic aciduria, of only pyrimidines nucleotides), which the red blood cell precursors, erythroblasts, need in large quantities for DNA replication. More context: A. Incorrect: Chemotherapy drugs that inhibit folate metabolism can lead to impaired DNA synthesis in rapidly dividing cells, including red blood cell precursors. Folate is essential for the de novo synthesis of nucleotides, including thymidine, which is crucial for DNA replication. When folate metabolism is inhibited, it can result in impaired nucleotide synthesis and anemia. B. Incorrect: Hereditary orotic aciduria: Hereditary orotic aciduria is a rare genetic disorder characterized by impaired pyrimidine nucleotide synthesis. Pyrimidines are essential for DNA replication. This condition can lead to megaloblastic anemia due to the inability of erythroblasts to synthesize sufficient nucleotides for DNA replication. C. Correct: Iron deficiency primarily affects the synthesis of hemoglobin, a protein within red blood cells responsible for oxygen transport. While iron is essential for various cellular processes, including DNA synthesis, it does not directly impair nucleotide synthesis. Iron deficiency anemia primarily results from inadequate hemoglobin production, not impaired nucleotide synthesis. D. Incorrect: Vitamin B12 deficiency: Vitamin B12 is required for the proper functioning of enzymes involved in nucleotide metabolism. Its deficiency can lead to impaired DNA synthesis and megaloblastic anemia, characterized by large and ineffective red blood cell production.

6. A patient of yours is concerned about having anemia due to iron deficiency. Which of the following statements is least likely to apply to such a condition? a. It is commonly caused by chronic blood loss b. It is the most common cause of anemia worldwide. c. It presents as a macrocytic hypochromic anemia. d. It presents as a microcytic hypochromic anemia.

Correct Answer: C Rationale: Iron deficiency will cause impaired synthesis of hemoglobin, resulting in red blood cells of smaller size (microcytic) and reduced coloration (hypochromic) when visualized by light microscopy. More context: A. Incorrect: This statement is true. Iron deficiency anemia is commonly caused by chronic blood loss, which could result from factors like heavy menstrual bleeding or bleeding in the gastrointestinal tract. The chronic loss of red blood cells necessitates their replacement, and this ongoing synthesis of new RBCs can deplete the body's iron stores, leading to iron deficiency and eventually iron deficiency anemia. B. Incorrect: This statement is accurate. Iron deficiency is indeed the most common cause of anemia globally. It can stem from inadequate dietary intake, impaired absorption, or chronic blood loss, and can affect various populations, from pregnant women to young children and the elderly. C. Correct: This statement is least likely to apply to iron deficiency anemia and is thus the @ Correct Answer. Iron deficiency anemia presents as a microcytic, hypochromic anemia, not a macrocytic one. Microcytic anemia involves red blood cells that are smaller than normal, while hypochromic indicates that the cells have reduced color (lower hemoglobin concentration). D. Incorrect: This statement is true. Iron deficiency anemia does indeed present as a microcytic hypochromic anemia. Iron is a critical component of hemoglobin, and its deficiency results in red blood cells that are smaller and paler than usual due to reduced hemoglobin synthesis.

2. A patient has been diagnosed with breast cancer that is staged at T1N1M0. Based on this information, which of the following statements is most accurate? a. The patient does not have a neoplasm. b. The patient has an in situ carcinoma c. The patient has a primary tumor and regional lymph node involvement. d. The patient has a primary tumor but no regional lymph node involvement. e. The patient has a primary tumor, regional lymph node involvement, and distant metastasis.

Correct Answer: C Rationale: Lesions are classified as T1-T4 based on their increasing size. T1 would indicate a primary tumor. N1-3 is used to denote nodal involvement. N1 would indicate the cancer has spread to 1 or 2 nearby lymph nodes. M0 indicates no metastases. Of the answer choices above, the one that best describes a T1N1M0 tumor is that "[t]he patient has a primary tumor and regional lymph node involvement." More context: 1. T (Tumor) - Describes the size and/or extent of the primary tumor. - Tx: Primary tumor cannot be measured or found. - T0: No evidence of a primary tumor. - Tis: In situ tumor (localized and has not spread). - T1-4: Denotes the size and/or extent of the primary tumor, with higher numbers indicating larger size or greater extent. 2. N (Nodes) - Describes the degree of regional lymph node involvement. - Nx: Regional lymph nodes cannot be evaluated. - N0: No cancer in regional lymph nodes. - N1-3: Increasing involvement of regional lymph nodes, with higher numbers indicating more extensive involvement or involvement of lymph nodes further from the primary tumor. 3. M (Metastasis) - Describes the presence of distant metastasis. - M0: No distant metastasis. - M1: Distant metastasis is present.

6. A 75-year-old female with dysarthria (speech disorder caused by muscle weakness) and hemiparesis (weakness on one side of the body) is found to have a tumor mass involving the right parietal lobe of the brain. Stereotactic needle biopsy is submitted to pathology where she receives a histologic diagnosis of central nervous system lymphoma. Her therapy includes rituximab and high-dose methotrexate. Her son asks how methotrexate works. Which of the following is the best explanation? A. It directly causes chain termination of DNA synthesis B. It directly causes termination of protein synthesis C. It is an inhibitor of dihydrofolate reductase and limits nucleotide availability D. It is an inhibitor of folinic acid and limits vitamin B12 availability

Correct Answer: C Rationale: Methotrexate inhibits synthesis of purines and pyrimidines by disrupting production of tetrahydrofolate (THF). It does not target the DNA polymerase. The drug's effect on the bone marrow can be ameliorated by administering folinic acid, also known as leucovorin, since folinic acid is converted to fully reduced methyltetrahydrofolate, a chemical that is beyond the block induced by methotrexate in dihydrofolate reductase (DHFR). More context: A. Incorrect: Methotrexate does not directly cause chain termination of DNA synthesis. This mechanism of action is more characteristic of nucleoside analogs, which incorporate into the DNA chain during replication and ultimately lead to premature termination of the chain. B. Incorrect: Methotrexate does not directly cause the termination of protein synthesis. Agents that directly inhibit protein synthesis typically act on the ribosomes, which is not the case with methotrexate. C: Incorrect: Methotrexate is a folate analog that inhibits dihydrofolate reductase (DHFR), an enzyme involved in the conversion of dihydrofolate to tetrahydrofolate. Tetrahydrofolate is crucial for the synthesis of purines and pyrimidines, which are building blocks of DNA and RNA. By inhibiting DHFR, methotrexate reduces the availability of nucleotides, which interferes with DNA synthesis and cell division, particularly in rapidly dividing cells like those of a tumor. D: Incorrect: Methotrexate does not inhibit folinic acid nor does it directly limit vitamin B12 availability. While folinic acid (leucovorin) is used to rescue normal cells from the toxic effects of methotrexate, it's not the target of methotrexate's action.

4. The image indicates two melanocytes with the letter "M". Which statement characterizes these cells: a. Because melanocytes move around destroying antigens in all the layers of the epidermis they are not attached to each other by desmosomes b. The pigment produced by melanocytes remains in the basal layer of the epidermis protecting the stem cells located there c. The epidermis of all humans contains about the same relative numbers of melanocytes d. The differences in skin pigmentation arise from differences in the number and size of melanocytes

Correct Answer: C Rationale: N/A More Context: A. Incorrect: Melanocytes do not move around the epidermis. Their primary function is not to destroy antigens but to produce melanin, a pigment that protects underlying cells from UV radiation. They are generally located in the basal layer of the epidermis and extend their dendrites between keratinocytes, transferring melanin to them. B. Incorrect: Melanocytes, which are indeed located in the basal layer of the epidermis, produce melanin, but the pigment doesn't only remain there. The melanin is transferred to keratinocytes in the surrounding area through cytocrine secretion, where it accumulates above the nuclei of these cells, helping to protect the DNA from UV radiation damage. C. Correct: All humans, regardless of skin color, have roughly the same number of melanocytes in their skin. The primary difference that contributes to the variety in skin color is not the number of melanocytes, but the number of melanosomes. D. Incorrect: As stated in explanation C, all humans typically have about the same number of melanocytes. Differences in skin pigmentation are not due to the number or size of melanocytes, but primarily due to variations in melanosomes. These variations can be influenced by genetic, hormonal, and environmental factors (like UV exposure).

3. When comparing the overlying epithelium to the underlying connective tissue, which of the following statements is TRUE? a. Fibroblasts will be more numerous in the epithelium relative to the connective tissue b. The epithelium will tend to contain more vascular structures than the connective tissue because of its higher metabolic needs c. Under healthy circumstances, the epithelium will be more cellular than the connective tissue

Correct Answer: C Rationale: N/A More Context: A. Incorrect: Fibroblasts are specialized cells found primarily in the connective tissue. They play a crucial role in producing the extracellular matrix, including collagen and other structural components. Epithelial tissues typically do not contain fibroblasts in significant numbers. B. Incorrect: Epithelial tissues are generally avascular, meaning they lack blood vessels. Nutrients and oxygen diffuse from the underlying connective tissue to nourish the epithelial cells. Connective tissues are more vascular because they provide support, transport nutrients, and are involved in immune responses. C. Correct: In histology, the epithelium is composed of closely packed cells that form protective barriers or lining tissues. Epithelial tissues are highly cellular and are characterized by cells tightly packed together. In contrast, connective tissues typically have fewer cells dispersed within an extracellular matrix of fibers and ground substance. This makes the epithelium more cellular than the connective tissue.

1. The type of epithelium lining these tubes has one layer of cuboidal cells. Based on its structure, where would you say it is found? a. Where protection from friction is needed b. Where substances in the lumen of the tube must cross the epithelium extremely fast c. Where the epithelial cells absorb and secrete simple substances from and into the lumen.

Correct Answer: C Rationale: N/A More context: A:Where protection from friction is needed→Has stratum lucidum, it's more stratified squamous (e.g. skin) B:Where substances in the lumen of the tube must cross the epithelium extremely fast →simple squamous structure A. Incorrect: Epithelia that provide protection from friction typically are stratified (multiple layers of cells) and often squamous (flattened) in shape, such as stratified squamous epithelium, to provide a more durable surface that can withstand wear and tear. A single layer of cuboidal cells does not provide substantial protection against friction due to its single-layer and cell shape. B. Incorrect: To facilitate rapid exchange or transfer of substances, a thin, flat type of epithelial cells, such as simple squamous epithelium, would be more appropriate because the flattened shape and single layer provide minimal distance and barriers for substances to traverse, facilitating rapid exchange. C. Correct: Simple cuboidal epithelium, which consists of a single layer of cuboidal cells, is often found in areas where absorption and secretion are primary functions. These cells provide a balance between providing some protective layering and maintaining a functional capacity to absorb and secrete substances, such as in various glands, ducts, and portions of the kidney tubules.

4. Relative to dense connective tissues like tendon, loose connective tissues (deep to epithelia) like the one pictured here are: a. Richer in collagen content b. Comprised of type II collagen c. More permissive to vascular structures d. Are stronger, provide stronger support

Correct Answer: C Rationale: N/A More Context: A. Incorrect: Loose connective tissues are not richer in collagen content compared to dense connective tissues. Dense connective tissues like tendons have a higher collagen content, which gives them their characteristic strength and tension-bearing ability. Loose connective tissue has fewer fibers and more cells and ground substance, which gives it a looser structure, enabling it to provide a supportive matrix and nutrient transport, but not as much strength. B. Incorrect: Type II collagen is not predominant in either loose connective tissue or tendons. Type II collagen is primarily found in cartilage, where it helps resist pressure and is essential for maintaining structural integrity. In contrast, loose connective tissue generally contains Type I collagen, as does dense connective tissue like tendons. C. Correct: Loose connective tissue is more permissive to vascular structures than dense connective tissue like tendons. Loose connective tissue often contains more cells, fewer fibers, and more ground substance, allowing it to provide a supportive and nutritive framework for adjacent structures, such as epithelia. This loose and cellular-rich structure also permits the passage of blood vessels, making it more permissive to vascular structures. D. I Loose connective tissues are not stronger and do not provide stronger support compared to dense connective tissues like tendons. The higher collagen content and densely packed fibers in tendons provide great tensile strength, making them excellent at bearing tension and providing strong support. Loose connective tissue, with its fewer fibers and more cells, is not structured to provide significant mechanical strength.

1. A university student is referred for evaluation of intermittent fevers, sweats, and 15 pounds of weight loss that she has sustained over the last three months. A cervical lymph node biopsy is reviewed by the pathologist, leading to a diagnosis of Hodgkin lymphoma. Which of the following statements is most likely to apply to this case? A. Even with appropriate therapy, survival at 5 years is poor B. Most cells on the lymph node biopsy are the hallmark Reed-Sternberg cells C. Nodular sclerosis is the most common histologic type D. Peak incidence occurs in middle age (40-60 years)

Correct Answer: C Rationale: Reed-Sternberg (RS) cells can be pathognomonic of Hodgkin lymphoma (HL), although they can rarely be seen in other lymphomas. Although the RS cell is the neoplastic cell in HL, it is outnumbered and surrounded by other cells that, presumably, form an immune response to this transformed cell. Thus, few of these diagnostic RS are seen on biopsy. The epidemiology of HL is characterized by a bi-modal age distribution, and characteristics are different in the two major age groups. Survival is generally considered good with appropriate therapy. Nodular sclerosis is the most common histologic type in HL. Most Context: A. Incorrect: Hodgkin lymphoma, especially when diagnosed at an early stage, typically has a good prognosis with appropriate therapy. The 5-year survival rate is generally quite high, often exceeding 80%. B.Incorrect: In Hodgkin lymphoma, the hallmark cells are Reed-Sternberg cells, but these cells typically make up a small fraction of the total cell population in the lymph node biopsy. The majority of the cells in the biopsy are typically other types of inflammatory and immune cells. C. Correct: Nodular sclerosis Hodgkin lymphoma (NSHL) is indeed the most common subtype, particularly among young adults. It often presents with lymphadenopathy, as in the case described, and is associated with characteristic "lacunar" Reed-Sternberg cells and bands of fibrosis demarcating nodules, hence the term "nodular sclerosis." D. Incorrect: Hodgkin lymphoma has a bimodal age distribution, with peaks in early adulthood (typically 15-35 years) and in those over 55 years.

19. A 45 year-old male with poorly controlled type-1 diabetes mellitus has persistent fevers, headaches, and nasal discharge for 2 weeks. The symptoms last even after he is given a course of amoxicillin for acute bacterial sinusitis. A CT is done and shows opacified maxillary sinuses and bony erosion into the orbital floor. Which of the following pathogens is most likely causing his disease? A. Candida albicans B. Coccidiomycosis C. Mucormycosis D. Streptococcus pneumoniae

Correct Answer: C Rationale: Rhino-orbital sinusitis is typically caused by invasive molds such as mucormycosis. More context: A. Incorrect. Although Candida can cause infections, it usually doesn't create the kind of severe sinus and bone issues described here, especially in the nose and eye area. It's more associated with skin and mucous membrane infections. B. Incorrect. This fungus does lead to respiratory infections, especially in certain parts of the U.S., but it generally doesn't cause the severe nose and eye (rhino-orbital) infections like the one described in this case. C. Correct. This fungus is known for causing serious infections, especially in people with poorly controlled diabetes. Mucormycosis can cause aggressive infections in the nose, sinus, and even eyes, matching the patient's symptoms and CT scan findings, making it the most likely cause of the disease in this situation. D. Incorrect. Even though this bacteria can cause sinus infections, the patient didn't get better with a commonly used antibiotic (amoxicillin), and this bacteria doesn't usually cause the severe type of infection, with bone damage, as seen in the CT scan.

2. In addition to cytotoxic chemotherapy, a patient with Burkitt's leukemia/lymphoma is given rituximab. Which of the following statements about rituximab is most accurate? A. It is a mainstay of treatment of Hodgkin lymphoma B. It is an anti-CD3 monoclonal antibody C. It is an anti-CD20 monoclonal antibody D. It is a tyrosine kinase inhibitor

Correct Answer: C Rationale: Rituximab targets CD20 on B cells and is often used in the management of non-Hodgkin's lymphoma along with other therapies. More Context: A. Incorrect: Rituximab is not a mainstay for the treatment of Hodgkin lymphoma. Although it is used in the treatment of various lymphomas, its primary use is in non-Hodgkin lymphomas, especially those derived from B cells. B. Incorrect: Rituximab targets CD20, not CD3. CD3 is usually present on T cells, and an anti-CD3 antibody would target them, not the B cells, which are the cells of concern in Burkitt's leukemia/lymphoma. C. Correct: Rituximab is an anti-CD20 monoclonal antibody. CD20 is a protein expressed on the surface of B cells. By targeting CD20, rituximab selectively binds to B cells, marking them for destruction by the immune system, which can be therapeutically beneficial in B cell malignancies like Burkitt's leukemia/lymphoma. D. Incorrect: Rituximab does not inhibit tyrosine kinases. It works by binding to CD20 on the surface of B cells. Tyrosine kinase inhibitors (TKIs) are a different class of drugs that work by inhibiting tyrosine kinases, which are enzymes involved in the activation of many cellular processes, including cell division and growth, and are not related to rituximab's mechanism of action.

2. Mike was very concerned when his son's daycare center was hit with several cases of diarrhea, which was characterized by small bloody stools. All of the children at the center were given antibiotics and the disease symptoms quickly disappeared. Public Health officials noted that small numbers of the infectious agent were needed for transmission of the disease. The organism was determined to be a gram-negative bacillus, lactose fermentation negative. Which of the following is the most likely cause of this diarrhea outbreak? a. Campylobacter jejuni b. Clostridioides difficile c. Shigella dysenteria d. Vibrio cholera

Correct Answer: C Rationale: Shigella is resistant to acidic conditions ("acid stable"), and between 10 and 100 bacteria taken into mouth can be sufficient to cause disease. Vibrio cholera is currently not a US pathogen and does not cause bloody stool. Campylobacter jejuni is a gram-negative curved rod and is much more sensitive to acidic conditions than Shigella dysenteria. More context: A. Incorrect: While Campylobacter jejuni is a gram-negative bacterium and can be associated with bloody diarrhea, it is often described as a curved rod or spiral-shaped bacterium, not a bacillus (rod-shaped). Also, it tends to be sensitive to acidic conditions and usually requires a larger infectious dose to cause disease compared to Shigella species. B. Incorrect: Clostridioides difficile is a gram-positive bacillus, so it does not fit the description of the causative organism being gram-negative. Furthermore, C. difficile typically causes diarrhea that may or may not be bloody but is generally associated with recent antibiotic use rather than being transmitted between individuals in an outbreak setting in healthy populations. C. Correct: Shigella dysenteria fits the description well as it is a gram-negative bacillus, does not ferment lactose, and can cause bloody diarrhea. It is notorious for its low infectious dose (as few as 10 organisms can cause disease due to its acid resistance), which aligns with the statement about small numbers being needed for transmission. Shigella outbreaks, often involving daycare centers or similar settings, can present with symptoms as described. D. Incorrect: Vibrio cholera is a gram-negative bacterium and is known to cause significant, often severe, watery diarrhea ("rice-water stools") rather than small, bloody stools. Additionally, V. cholera is typically not associated with outbreaks in daycare settings in countries where the disease is not endemic. Also, it does not typically present with bloody diarrhea.

16. A patient presents with a diffuse, confluent, erythematous, sandpaper-like rash characteristic of scarlet fever secondary to Streptococcus pyogenes. Which one of the following statements describes most accurately the treatment of choice and the rationale behind it? a. Not to prescribe any antibiotics because infections with S. pyogenes do not warrant treatment. b. To prescribe azithromycin because it is preferable to beta-lactam antibiotics for S. pyogenes infections. c. To prescribe amoxicillin because S. pyogenes is uniformly susceptible to all beta-lactam antibiotics. d. To prescribe amoxicillin-clavulanate because production of beta-lactamases is common among S. pyogenes isolates.

Correct Answer: C Rationale: Streptococcus pyogenes remains exquisitely susceptible to penicillins, including amoxicillin. Azithromycin is a macrolide and should only be used if allergy precludes the use of penicillins. S. pyogenes infections do warrant treatment. More Context: A. Incorrect. Infections caused by Streptococcus pyogenes (Group A Streptococcus) typically require antibiotic treatment to prevent complications such as rheumatic fever and acute glomerulonephritis. Scarlet fever, which is caused by S. pyogenes, is one of the conditions that may require antibiotic treatment. B. Incorrect: While azithromycin is effective against many bacterial infections, beta-lactam antibiotics like amoxicillin are the first-line treatment for Streptococcus pyogenes infections. Beta-lactam antibiotics are highly effective against this bacterium, and there is no specific advantage to using azithromycin as the first-line treatment for streptococcal infections. So, this statement is not the most accurate choice. C. Correct: Streptococcus pyogenes is highly susceptible to beta-lactam antibiotics, including amoxicillin. Beta-lactam antibiotics are considered the treatment of choice for streptococcal infections, including scarlet fever. D. Incorrect: Streptococcus pyogenes (Group A Streptococcus) is not known for producing beta-lactamases, and therefore, there is no need to use amoxicillin-clavulanate (which is used to counteract beta-lactamase production) as the first-line treatment. Standard amoxicillin is effective against S. pyogenes.

7. Which of the following statements is most accurate when responding to a patient's question regarding the benefits of using sunscreen SPF 30? a. Approximately 30% of total ultraviolet (UV) radiation is blocked. b. Approximately 30% of UVB exposure is blocked. c. It takes 30 times more UV to develop erythema than without its application. d. The sunscreen, by concentration, contains 30% of UVB filter reagent.

Correct Answer: C Rationale: The Sun Protection Factor (SPF) is the ratio of the amount of UV radiation required to produce a minimally detectable sunburn on sunscreen-protected skin relative to the amount required on unprotected skin. When properly applied, a sunscreen with a SPF of 30, allows 1/30 of erythemogenic UV photons to reach the skin. Other responses were incorrect: ~97% of UVB is blocked with broad spectrum SPF 30; the UVA protection needs to be greater than 1/3 that of the UVB protection; and the maximum allowed concentrations of the organic UV filters in the sunscreens currently range between 3% and 15%. More Context: A. Incorrect: This is not an accurate depiction of how SPF works. An SPF 30 sunscreen blocks approximately 97% of UVB rays, not just 30% of total UV radiation. B. Incorrect: Again, this is inaccurate as SPF 30 blocks approximately 97% of UVB radiation, not merely 30%. C. Correct: This statement is accurate in describing SPF. SPF (Sun Protection Factor) is a measure of a sunscreen's ability to protect the user from UV radiation. Specifically, an SPF of 30 means that theoretically, it would take 30 times more UV radiation to cause sunburn in skin protected with the sunscreen as compared to unprotected skin. D. Incorrect: The SPF number is not indicative of the percentage concentration of UVB filtering agents in the sunscreen. The maximum allowed concentrations of organic UV filters in sunscreens typically range between 3% and 15%, not 30%.

2. Which of the following statements best characterizes the histological structure shown in the image in blue color and labeled "BM"? a. Blood vessels can freely penetrate it b. Nerves run through underlying tissue but never penetrate it. c. In malignant growth, the epithelium crosses over it. d. It is regenerated by cells that are present within it.

Correct Answer: C Rationale: The basement membrane is an acellular structure that allows for the passage of nerves but not blood vessels. In malignant growth, transformed epithelial cells cross the basement membrane to migrate to other tissues. More Context: A. Incorrect: This statement is incorrect because the basement membrane typically acts as a barrier that restricts blood vessels from freely penetrating it. Blood vessels are primarily located in the underlying connective tissue. B. Incorrect: Nerves DO penetrate the basement membrane. C. Correct: In cases of malignant (cancerous) growth, the epithelial cells can breach the basement membrane and invade the underlying tissue. This behavior is characteristic of malignancy and distinguishes it from benign growths. It directly characterizes the behavior of the basement membrane in a specific pathological context. D. Incorrect: The basement membrane itself is not composed of cells but is made up of a dense matrix of proteins and other molecules. While it can be regenerated and repaired, it is not by cells within the basement membrane since it is acellular. Cells from adjacent tissues, such as epithelial or endothelial cells, contribute to its regeneration and maintenance. While it lacks cells, the basement membrane is essential for maintaining tissue integrity and function.

7. A 62-year-old farmer presents with a complaint of rashes and a few sores. They have a low-grade fever and general malaise. You biopsy a lesion, resulting in the images shown below. Which of the following is the most likely primary pathological process? a. Acute inflammation b. Chronic granulomatous inflammation c. Chronic inflammation d. The patient has an abscess. e. The patient is fine as this appears to be normal skin.

Correct Answer: C Rationale: The cells in the image are lymphocytes. They contain a dark, single nucleus with a thin rim of surrounding cytoplasm. Lymphocytes can be seen in chronic inflammatory responses. More Context: A. Incorrect: Acute inflammation involves diffuse neutrophils. Acute inflammation is a rapid and short-term response of the body to injury or infection. It typically involves neutrophils and may lead to symptoms like redness, swelling, heat, and pain. The symptoms described in the case (low-grade fever, malaise, rashes, and sores) do not align with the characteristics of acute inflammation. Additionally, the biopsy showing lymphocytes is not consistent with acute inflammation. B. Incorrect: Chronic granulomatous inflammation is characterized by the presence of granulomas, which are collections of immune cells, including macrophages, surrounded by lymphocytes. It is often associated with chronic infections or autoimmune diseases. The biopsy showing lymphocytes suggests the possibility of chronic inflammation, but the specific presence of granulomas is not mentioned in the case. There are two types of granulomas- Caseating and noncaseating. Caseating granulomas feature a distinctive "cotton candy" central necrosis and a periphery of lymphocytes, histiocytes, and multinucleated Langhans giant cells, whereas noncaseating granulomas lack central necrosis, presenting a more solid, well-defined structure composed chiefly of macrophages and lymphocytes. C. Correct: Chronic inflammation involves Lymphocytes, Macrophages, Plasma. Chronic inflammation is a long-term response to tissue injury, infection, or foreign substances. It can involve the infiltration of lymphocytes, macrophages, and other immune cells into the affected area. The biopsy showing lymphocytes is suggestive of chronic inflammation. The patient's low-grade fever, malaise, and skin symptoms are consistent with chronic inflammation. D. Incorrect: An abscess is a localized collection of pus within a tissue, often resulting from an acute infection. It is characterized by pain, swelling, and redness. While the patient has sores, the overall clinical presentation, including low-grade fever and malaise, does not strongly support the pre

14. A patient is growing Staphylococcus aureus from her blood. She is not responding to nafcillin. 'Sensitivities' (antibiotic sensitivity tests) are pending. Which of the following mechanisms is most likely to be responsible for resistance to nafcillin? a. An efflux pump b. Penicillinase hydrolyzes the β-lactam ring c. The mecA gene produces an altered penicillin binding protein (PBP)2a that weakly binds methicillin d. Thickened cell wall

Correct Answer: C Rationale: The decreased ability of methicillin to bind to PBP2a and interrupt peptidoglycan synthesis via alteration in PBP2a by the mecA gene is what causes methicillin resistance in methicillin-resistant Staphylococcus aureus (MRSA). Penicillinase is responsible for penicillin resistance in S. aureus but methicillin is not hydrolyzed by penicillinase (beta-lactamase). A thickened cell wall plays a role in reduced susceptibility to vancomycin and daptomycin in certain strains of S. aureus. Efflux pumps are common resistance mechanisms in gram-negative bacteria. More Context: A. Incorrect: An efflux pump is not the primary mechanism associated with nafcillin resistance in Staphylococcus aureus. Efflux pumps are often involved in resistance to multiple classes of antibiotics especially in gram-negative bacteria, but this is not the primary resistance mechanism for nafcillin in S. aureus. B. Incorrect: While penicillinase, which hydrolyzes the beta-lactam ring, is a mechanism of resistance against penicillins, nafcillin is a penicillinase-resistant penicillin. Thus, this mechanism does not explain the resistance to nafcillin in this scenario. C. Correct: The mecA gene encodes an altered penicillin-binding protein, PBP2a, which has reduced affinity for binding to beta-lactam antibiotics, such as methicillin and nafcillin, thereby conferring resistance. This is a common mechanism of resistance in Methicillin-Resistant Staphylococcus aureus (MRSA). D. Incorrect: A thickened cell wall is not the primary mechanism for nafcillin resistance in S. aureus. Thickening of the bacterial cell wall is more typically associated with resistance or intermediate resistance to vancomycin and does not confer resistance to beta-lactam antibiotics like nafcillin.

18. The energy metabolism of most cancer cells is similar to that of cells in the early phase of development in that metabolism of glucose produces high levels of lactate even in the presence of molecular oxygen. This phenomenon, which is referred to as the Warburg effect, is mostly associated with an increase in which of the following? a. Electron transport chain b. Fatty acid beta-oxidation c. Glucose transport and phosphorylation d. Pyruvate utilization by mitochondria

Correct Answer: C Rationale: The increased metabolism of glucose and of lactate production in cancer cells is associated with increased protein expression levels of diffusion facilitators of the GLUT family (to increase the ability to uptake glucose via diffusion facilitation) and hexokinase (the enzyme that attaches a phosphate group to glucose to prevent it from leaving the cell). Expression of the enzyme that mediates conversion of pyruvate (resulting from glycolysis) into lactate is also increased in cancer cells. More Context: A. Incorrect: Electron transport chain is not predominantly associated with the Warburg effect. The Warburg effect refers to the preference of cancer cells to undergo glycolysis, producing lactate in the presence of oxygen, rather than sending pyruvate, the end-product of glycolysis, to the mitochondria for oxidative phosphorylation in the electron transport chain. So, the Warburg effect actually demonstrates a reduction in reliance on the electron transport chain for energy production in cancer cells. B. Incorrect: Fatty acid beta-oxidation is not increased in most cancer cells exhibiting the Warburg effect. Instead, these cells preferentially utilize glycolysis for energy production even in the presence of oxygen, which is different from fatty acid beta-oxidation, a metabolic pathway that breaks down fatty acids to generate acetyl-CoA, which can enter the citric acid cycle, and NADH and FADH2, which are used in the electron transport chain. C. Correct: Glucose transport and phosphorylation are increased in cells exhibiting the Warburg effect. These cells have an increased uptake of glucose and its conversion to lactate even in the presence of oxygen, thus involving increased glucose transport into the cells and increased phosphorylation of glucose to trap it within the cells, and facilitate its metabolism through glycolysis. D. Incorrect: Pyruvate utilization by mitochondria is not typically increased in cancer cells displaying the Warburg effect. Instead, despite the availability of oxygen, these cells prefer to convert pyruvate, the end product of glycolysis, into lactate rather than sending it into the mitochondria for further metabolism in the citric acid cycle, a p

15. A 40-year-old female presents with dyspnea on exertion for a few weeks. She has had some low-grade fevers. She denies any nausea, vomiting or diarrhea, but she has had some loss of appetite and has lost about 10 lbs in the last 2 months. Her vital signs are as follows: temperature 38.3ºC, heart rate 90 beats per minute, blood pressure 100/78 mm Hg, respiratory rate 20 per minute, and oxygen saturation 89%. Her exam is notable for fine inspiratory crackles, but otherwise no rashes or significant lymphadenopathy. Her chest X-ray shows fine reticular interstitial infiltrates. Labs are notable for a white count of 2100 per mm (low) and a lactate dehydrogenase (LDH) of 500 IU/L (high). Her rapid HIV antibody test is positive. Which of the following is most likely to confirm the diagnosis in this patient? A. Excisional biopsy of lymph node for histopathology B. Expectorated sputum bacterial cultures C. Pneumocystis carinii (jiroveci) pneumonia direct fluorescent antibody test of induced sputum D. Urine Histoplasma antigen

Correct Answer: C Rationale: This clinical presentation is consistent with Pneumocystis carinii (jiroveci) pneumonia. Given how long her symptoms have been going on, a bacterial pneumonia is unlikely. There is no need for a lymph node biopsy if her lymph nodes are not enlarged. Histoplasmosis typically presents as granulomatous disease. More context: A. Incorrect: This means taking a sample of lymph node tissue to look at it closely under a microscope. But, since the patient doesn't have swollen lymph nodes, this isn't needed. B. Incorrect: This would involve testing mucus (sputum) that the patient coughs up to check for bacteria that might cause pneumonia. But, because the patient's symptoms have been happening for several weeks and have additional findings, bacterial pneumonia isn't likely the cause. C. Correct: The patient's symptoms, lung changes seen on X-ray, and being immunocompromised (due to HIV and low white blood cell count) strongly point to a specific kind of pneumonia caused by the fungus *Pneumocystis jiroveci*. This test involves checking the sputum for this particular fungus, making it the best choice given the symptoms and findings. D. Incorrect: This test checks the urine for evidence of a different fungus called *Histoplasma*. But, because of the patient's symptoms and X-ray results, the other type of pneumonia (PJP) is more likely, so this isn't the best test to choose. In simpler terms: The patient has been sick for a few weeks with symptoms and X-ray results that suggest a type of pneumonia that often occurs in people with weakened immune systems (like from HIV). So, option C is the best test to confirm this because it checks for the specific cause of that pneumonia.

4. A patient presents with a skin lesion that is biopsied. Based on the histological images shown below, which of the following is the most likely primary pathological process? a. Acute inflammation b. In situ carcinoma c. Malignant neoplasm d. Noncaseating granuloma e. Ulceration

Correct Answer: C Rationale: This image shows no neutrophils, plasma cells or lymphocytes. Rather, we see an extensive disruption to the dermal-epidermal border. The tissue is completely disorganized, the healthy architecture of the skin is disrupted, and the dermis shows irregular structures that do not resemble the healthy loose connective tissue (dermis). This is a characteristic of a malignant tumor in the skin. More Context: A. Incorrect: Acute inflammation would typically present with neutrophils, edema, and possibly other signs of inflammation in the histological sample, which are not described to be seen in the given sample. B. Incorrect: While in situ carcinoma might disrupt tissue architecture, it does not invade beyond the epithelial layer from which it arises. It remains localized and doesn't penetrate the basement membrane. C. Correct: The described histological features such as extensive disruption to the dermal-epidermal border, disorganized tissue, and irregular structures in the dermis are characteristic of a malignant neoplasm, which involves abnormal and uncontrolled cell growth that invades surrounding tissues. D. Incorrect: Noncaseating granulomas usually involve the aggregation of macrophages and other immune cells, leading to a distinct appearance on histological analysis, such as a well-formed granuloma which is not described in the available information. E. Incorrect: While ulceration may disrupt normal tissue architecture, it generally involves loss of the epithelial layer and often shows signs of inflammation, necrosis, or healing processes (like granulation tissue formation) which are not described in the provided details.

3. A 79-year-old male comes to your clinic with a recent diagnosis of acute myeloid leukemia (AML) based on a bone marrow biopsy done to evaluate neutropenia and thrombocytopenia. Which of the following features is least likely to develop in this patient? A. Disseminated intravascular coagulation B. Enlarged spleen (splenomegaly) C. Erythrocytosis D. Leukostasis syndrome

Correct Answer: C Rationale: Typically, the number of red cells is significantly reduced in acute leukemia. Most patients have anemia because marrow production of cells of erythroid lineage are disrupted by the clonal proliferation of immature myeloid blasts that replace the marrow space and all other sites of hematopoiesis. Leukostasis is defined as the intravascular accumulation of leukocytes causing obstruction of blood flow in the setting of hyperleukocytosis. More Context: A. Disseminated intravascular coagulation (DIC): Disseminated intravascular coagulation (DIC) can occur in patients with acute myeloid leukemia (AML). AML can lead to abnormal activation of the coagulation cascade, resulting in DIC.This happens because the abnormal myeloid cells in AML may release various substances that activate the coagulation cascade, leading to small clots throughout the bloodstream. Meanwhile, as these clotting factors get used up in forming these widespread small clots, bleeding risks elsewhere in the body increase due to the unavailability of clotting factors, hence, causing both clotting and bleeding issues which are characteristic of DIC. B. Enlarged spleen (splenomegaly): Enlarged spleen (splenomegaly) is a common feature in some cases of AML. The spleen can get infiltrated by these abnormal leukemic cells, which disrupts its normal function and architecture, causing it to enlarge. Such a scenario might lead to an array of clinical presentations and potential complications, like pain, rupture, or contributing to cytopenias (due to sequestration of cells). C. Erythrocytosis: Erythrocytosis, characterized by an increased number of red blood cells, is quite unlikely in AML. AML generally leads to a decrease in the effective production of normal blood cells (including red blood cells) due to the overcrowding of bone marrow by abnormal myeloid blast cells. Therefore, the typical manifestation related to red blood cells in AML is anemia (a deficiency of red cells or hemoglobin), not erythrocytosis. D. Leukostasis syndrome: Leukostasis syndrome, characterized by the abnormal accumulation of leukemic blasts in the blood vessels, is a potential complication of AML. It can lead to symptoms such as shortness of

10. An autosomal-recessive disease is reported to affect 1 every 2,500 births in a particular population. Assuming that the conditions for Hardy-Weinberg equilibrium are met, which of the following is the best estimate of the carrier frequency in that population? a. 1% b. 2% c. 4% d. 8%

Correct Answer: C Rationale: Under the conditions of Hardy-Weinberg equilibrium, the incidence of an autosomal-recessive condition is q^2 and the carrier frequency is ~2q. Accordingly, the carrier frequency should be = 2 x 1/√2500 = 2/50 = 1/25 = 4% More context: To find the carrier frequency, we can use the Hardy-Weinberg equation. Let's say that "q" is the frequency of the disease allele, and "p" is the frequency of the normal allele. According to the Hardy-Weinberg principle: p2+2pq+q2=1 Given that the disease is autosomal recessive, and its frequency (i.e., q2) is given as 1/2500 = 0.0004, we can find "q" by taking the square root of 0.0004. The square root of 0.0004 is 0.02. Now, to find "p" (since p + q = 1) p=1−q p=1−0.02 p=0.98 Now, we can find the carrier frequency, which is 2pq: 2pq=2×0.98×0.022 2pq=0.0392 So, the carrier frequency is 0.0392, or 3.92%, i.e. 4%.

14. A 65-year-old female has felt increasingly fatigued during the past 9 months. On physical examination, she has decreased sensation to touch in her lower extremities bilaterally. Laboratory studies show: hemoglobin 10.1 g/dL (low), hematocrit 31.2% (low), and mean corpuscular volume (MCV) 120 fL (high). Microscopic examination of the peripheral blood smear shows red blood cells that have macrocytosis and neutrophils with hypersegmentation of nuclei. Laboratory testing for which of the following nutrients is most likely to show a deficiency state? a. Iron b. Vitamin B9 (folate) c. Vitamin B12 (cobalamin) d. Vitamin K

Correct Answer: C Rationale: Vitamin B12 (cobalamin) deficiency is a cause for megaloblastic anemia, as is folic acid deficiency. Note that the lack of B12 can also lead to subacute combined degeneration of the spinal cord, which commonly presents with sensory deficits, paresthesia, weakness, ataxia, and gait disturbance. Folate deficiency can lead to megaloblastic anemia but not neurologic deficits. Iron deficiency leads to diminished synthesis of heme, and erythropoiesis is modified by 'downsizing' the RBCs with less hemoglobin. Finally, Vitamin K deficiency in itself does not cause anemia. More Context: A. Incorrect: An iron deficiency typically leads to microcytic anemia, characterized by a low mean corpuscular volume (MCV), not macrocytic anemia which is characterized by an increased MCV as in the patient's case. Therefore, this option is not consistent with the presented clinical and laboratory findings (high MCV, macrocytosis, and neutrophils with hypersegmented nuclei), making it incorrect. B. Incorrect: Folate deficiency can cause megaloblastic anemia, which is characterized by macrocytic red blood cells, but it does not typically result in neurological deficits like decreased sensation to touch in the lower extremities and hypersegmented neutrophils. The neurological symptoms in this case are more indicative of a vitamin B12 deficiency. C. Correct: Vitamin B12 (cobamalin) deficiency can cause macrocytic anemia, as evidenced by high MCV and macrocytosis in red blood cells and can also lead to hypersegmentation of neutrophil nuclei, all of which are consistent with the laboratory findings presented. Furthermore, vitamin B12 deficiency can cause neurologic abnormalities, such as decreased sensation, which matches the physical examination findings (decreased sensation to touch in the lower extremities bilaterally). Thus, this option aligns with all the provided clinical and laboratory findings, making it the @ Correct Answer. D. Incorrect: Vitamin K deficiency primarily affects the clotting cascade and does not typically lead to anemia or neurological deficits like those described in this case. Vitamin K deficiency is more associated with bleeding disorders.

15. *Initiation of warfarin treatment does not result in immediate anticoagulation effects after having reached pharmacologically active levels in blood. Which of the following statements explains most accurately the apparent delay in an observable warfarin anticoagulant effect? a. The mean plasma half-life of warfarin is approximately 40 hours. b. Warfarin binding to the vitamin K-epoxide reductase complex is dependent on heparin. c. Warfarin does not affect the activity of circulating coagulation factors II, VII, IX, and X in plasma since they already contain functional gamma-carboxylated glutamate residues. d. Warfarin has low oral bioavailability.

Correct Answer: C Rationale: Warfarin is an antagonist of vitamin K, a necessary element in the synthesis of clotting factors II, VII, IX and X as well as the anticoagulant proteins C and S. These factors and proteins are biologically inactive without carboxylation of certain glutamic acid residues. This carboxylation process requires a reduced vitamin K as a cofactor and occurs primarily in the liver. Antagonism of vitamin K, or a deficiency of this vitamin, reduces the rate at which these carboxylated factors and proteins are synthesized, thereby creating a state of anticoagulation. Therefore, the anticoagulant activity of warfarin depends on the clearance of functional clotting factors already present in the systemic circulation at the start of the drug treatment. The clearance of these clotting factors is determined by their half-lives. The earliest changes in the International Normalized Ratio (INR) are typically noted 24 to 36 hours after a first dose of warfarin is administered. These changes are due to the clearance of functional factor VII, which is the vitamin K-dependent clotting factor with the shortest half-life (six hours). However, the early changes in the INR are deceptive because they do not actually affect the body's physiologic ability to halt clot expansion or form new thromboses. The actual antithrombotic effect of warfarin, or the inability to expand or form clots, is not present until approximately the fifth day of therapy. This effect depends on the clearance of functional factor II (prothrombin), which has a half-life of approximately 40 hours in patients with normal hepatic function. Other responses, here as correctly written or qualified: Warfarin mean plasma half-life is approximately 40 hours but that parameter is used to determine dosing schedules, not pharmacodynamic activity. Vitamin K epoxide reductase complex is not dependent on heparin- epoxide binding. Finally, warfarin has high oral bioavailability (~ 100%). More context: A. Incorrect: Warfarin's long half-life does contribute to its delayed onset of action, but it is not the primary reason for the delay. The half-life determines how long the drug remains in the body, but it doesn't explain why it takes time to achiev

15. A patient with metastatic cancer experiences a dramatic loss of skeletal muscle mass. Which of the following statements is the most accurate response to the question of whether (or not) protein catabolism can yield energy in the form of ATP? a. No, because the catabolism of proteins releases amino acids and caloric energy (heat), none of which can be used to make ATP. b. No, because the catabolism of proteins yields mostly uric acid, which is eliminated in urine. c. Yes, because the catabolism of proteins yields amino acids, which (upon removal of the alpha-amino group) generate alpha-keto-acids that can enter energy-producing catabolism. d. Yes, because the catabolism of proteins yields lactate, which can enter the TCA cycle.

Correct Answer: C Rationale: While the breakdown of proteins into amino acids per se does not generate ATP, the amino acids can be converted into alpha-keto-acids (by removal of the amino group attached to the so-called "alpha" carbon), which can enter various catabolic pathways that eventually produce ATP (mostly through the electron transport chain and ATP synthase). More Context: A. Incorrect: While it is true that protein catabolism releases amino acids and heat energy, these amino acids can indeed be used to make ATP indirectly. Amino acids can be converted into intermediates that enter various energy-producing pathways, such as the citric acid cycle (TCA cycle) and the electron transport chain, ultimately leading to ATP production. B. Incorrect: Protein catabolism does not "mostly" yield uric acid; it primarily yields amino acids and other intermediates that can be used for various metabolic processes, including energy production. Uric acid is a waste product and is not a major source of energy production. C. Correct: Protein catabolism indeed yields amino acids, which can be converted into alpha-keto-acids through the removal of their alpha-amino groups. These alpha-keto-acids can then enter energy-producing catabolic pathways, such as the citric acid cycle, where they can be further metabolized to generate ATP. D. Incorrect: Protein catabolism does not primarily yield lactate. Lactate is typically produced from the catabolism of carbohydrates (e.g., glucose) during anaerobic metabolism. While lactate can be converted into pyruvate and enter the TCA cycle under certain conditions, it is not a direct product of protein catabolism.

1. The relative large membrane area and thinness of this epithelium enables vital gases to readily diffuse through and into the underlying tissue. Which of the following are this epithelium and the organ/structure it is found in? a. Pseudostratified ciliated epithelium - trachea b. Simple columnar epithelium - duodenum c. Simple cuboidal epithelium - renal tubules d. Simple squamous epithelium - lung alveoli

Correct Answer: D Rationale: Simple squamous epithelia are a one single flat cell layer epithelium. This type of epithelia allow for the quick passage of small molecules and gases. They are found lining the alveoli and blood vessels. More Context: A. Incorrect: The lung alveoli are tiny air sacs in the lungs where gas exchange occurs. Simple squamous epithelium is characterized by a single layer of flat, thin cells, which facilitates rapid diffusion of gases across the membrane. This option is the @ Correct Answer because it accurately matches the description provided in the question. B. Incorrect: Pseudostratified ciliated epithelium is found in the respiratory tract, including the trachea. While it has cilia that help with mucus clearance, it is not primarily responsible for gas exchange. C. Incorrect: Simple columnar epithelium is found in the digestive tract, including the duodenum. Its main function is absorption and secretion in the digestive process, not gas exchange. D. Correct: Simple cuboidal epithelium lines various parts of the renal (kidney) tubules, which are involved in the filtration and reabsorption of substances from urine. It is involved in fluid and electrolyte balance but not in gas exchange.

3. Which of these cells is a fibroblast? a. Top left b. Second from right c. Top right d. Bottom left e. second from the top left

Correct Answer: D Rationale: Fibroblasts are spindle shaped​ and are characterized by having an oval-shaped nucleus. More Context: Introduction to Histology A. Top left: Chondrocytes ○ Chondrocytes produce and maintain the cartilage matrix, providing flexibility and cushioning. Found within cartilage, including joints, the nose, ears, and bone ends. Appear as rounded cells within lacunae (small spaces) surrounded by a gel-like matrix containing collagen and proteoglycans. B. Second from right: Venule or arteriole 2nd from right ○ Arterioles are small blood vessels that regulate blood flow and are mainly composed of smooth muscle cells. Venules are small blood vessels that collect blood from capillaries, return it to the heart, and allow white blood cells to exit into tissues. They contain endothelial cells and connective tissue. C. Top right: Adipose cells ○ Stores energy as fat, provides insulation, and cushions organs. Found beneath the skin and around organs. Adipocytes, when viewed under a microscope, appear as large, round cells filled with a single, prominent lipid droplet. The nucleus and organelles are pushed to the cell's periphery due to the abundance of stored fat D. Bottom left: Fibroblast ○ Fibroblasts are connective tissue cells found throughout the body, including the skin, tendons, ligaments, and various internal organs. They contribute to tissue repair and maintenance in these locations. E. Second from the top left: Plasma cells ○ Plasma cells are a type of white blood cell (B lymphocyte) that produces antibodies (immunoglobulins) to help the immune system fight infections and pathogens. Plasma cells are found in various tissues, primarily in the bone marrow, lymph nodes, and spleen, where they generate antibodies in response to antigens. Under a microscope, plasma cells have a distinctive appearance, with an eccentric or "clock-face" nucleus and abundant cytoplasm. This appearance is due to the extensive production of antibodies, which fill the cytoplasm and give it a characteristic look

10. Which of the following statements most accurately characterizes FDA regulatory issues regarding Biosimilars? A. Biosimilars are synthesized by the same methods as the reference product (RP). B. Biosimilars need to have the same primary structure and posttranslational modifications. C. Comparison of the properties of a biosimilar with its corresponding RP can be based on historical data of dosage form, safety, strength, and route of administration developed for the RP. D. Equivalence trials need to demonstrate no clinically meaningful differences between the RP and the innovator product in terms of safety, purity, and potency.

Correct Answer: D Rationale: Clinical studies with biosimilars must demonstrate no clinically meaningful differences between itself and its RP in terms of safety, purity, and potency. The biosimilar and its RP have the same primary structure but not posttranslational modifications (e.g., glycosylation), thus minor differences in the clinically inactive components may exist. Reminder: Even though we'll talk about generic drugs more later, remember that biosimilars aren't the same as generic drugs. Generics are exact copies, while biosimilars are very, very similar but not identical. So, they aren't the "generics" of biologics. More context: A. Incorrect. Biosimilars don't need to be made using the exact same methods as the reference product. They need to work the same way, but they can be made differently. B. Incorrect. Biosimilars must have the same primary structure (the sequence of amino acids) as the reference product but can have small differences in other modifications that happen after the initial protein is made, as long as they don't affect safety or effectiveness. C. Incorrect. You can't only use old data about the original product to show a biosimilar is the same. They need to be directly compared in studies to show they work similarly and are safe. D. Correct. Trials for biosimilars need to show that there are no meaningful differences between the biosimilar and the reference product in how safe, pure, and potent they are.

9. Which of the following statements regarding the pharmacokinetics of monoclonal antibodies (mAb) is most accurate? A. mAb dosage needs to be reduced in liver failure. B. mAb dosage needs to be reduced in renal dysfunction. C. mAb metabolism occurs primarily by CYP 450 3A4. D. mAb plasma half-life increases with degree of 'humanization'.

Correct Answer: D Rationale: A greater degree of 'humanization' of mAb allows for more interaction with, and uptake by, the FcRn and subsequent recycling, which accounts for longer mAb plasma half-lives. The mAb dosage need not be reduced in renal or liver dysfunction since mAbs are not metabolized in the liver or cleared by the kidney. Catabolism of mAbs is a function of lysosome or ubiquitin-proteasome degradation. More context: A. Incorrect. mAbs (monoclonal antibodies) are big molecules, and unlike small drug molecules, they don't rely on the liver for breakdown or elimination. Therefore, if the liver is not working well (liver failure), it doesn't particularly impact how mAbs are handled by the body. B. Incorrect. mAbs are quite large compared to other drug substances. Kidneys, which are involved in filtering and removing waste, typically don't filter out large molecules like mAbs. So, even if the kidneys are not working well (renal dysfunction), it doesn't require a change in mAb dosage. C. Incorrect. The CYP 450 3A4 enzyme is known for breaking down many drugs in the liver, but mAbs are not notably affected by this enzyme. Instead of being broken down in the liver, mAbs are usually broken down into smaller pieces (amino acids and peptides) throughout the body by different mechanisms (not primarily in the liver). D. Correct. "Humanization" means modifying the mAb to make it resemble human antibodies more closely, thus making it less likely to be attacked by the human immune system. When mAbs are more "human-like," the body doesn't try to get rid of them as quickly, allowing them to stay in the blood (plasma) longer (increased half-life). This happens through a neat recycling process involving a special receptor (FcRn), which effectively "saves" the mAb from being broken down and helps it to stay active in the body for a longer time.

4. The son of a 79-year-old patient with acute myeloid leukemia (AML) asks why his father is not producing platelets. Impairment (in the setting of acute leukemia) of which of the following normal processes is the best explanation? A. Excessive proliferation B. Maturation arrest C. Monoclonal hematopoiesis D. Polyclonal hematopoiesis

Correct Answer: D Rationale: Acute leukemia is characterized by maturation arrest, resulting in an excess proliferation of blasts that do not mature in vivo. This the result of (mono)clonal hematopoiesis. Polyclonal hematopoiesis is representative of the normal state of affairs in blood cell production. More context: A. Incorrect: Excessive proliferation of immature myeloid cells is a characteristic feature of acute myeloid leukemia (AML), but it is not the primary reason for impaired platelet production. The main issue in AML is the overcrowding of the bone marrow by these immature cells, which can lead to a decrease in the production of normal blood cells, including platelets. B. Incorrect: Maturation arrest is a key feature of AML, but it does not directly explain impaired platelet production. The maturation arrest primarily affects the myeloid lineage, leading to an accumulation of immature myeloid cells (blast cells) in the bone marrow. Platelet production is impaired as a secondary consequence of this disruption in normal hematopoiesis. C. Incorrect: Monoclonal hematopoiesis refers to the presence of a single dominant clone of hematopoietic stem cells. While it can be associated with an increased risk of developing AML, it is not the direct cause of impaired platelet production in AML. D. Incorrect: Polyclonal hematopoiesis refers to the presence of multiple, genetically distinct clones of hematopoietic stem cells. In AML, the malignant myeloid cells (blast cells) compete with normal hematopoietic stem cells in the bone marrow. This competition can lead to impaired production of normal blood cells, including platelets. Therefore, polyclonal hematopoiesis is the best explanation for impaired platelet production in the setting of acute leukemia.

12. Blood cultures from a patient are growing gram-positive cocci. Which of the following laboratory criteria would establish Staphylococcus aureus, rather than Streptococcus pyogenes, as the causative organism? a. Growth on blood agar b. Motility c. Presence of gram-positive cocci d. Production of catalase

Correct Answer: D Rationale: Both are Gram-positive cocci that grow on blood agar. Neither of them is motile. Only Staphylococci produce catalase. More Context: A. Incorrect: Growth on blood agar is not a distinctive feature for Staphylococcus aureus as both Staphylococcus aureus and Streptococcus pyogenes grow on blood agar. B. Incorrect: Motility is not a distinguishing factor between Staphylococcus aureus and Streptococcus pyogenes as neither of them is motile. C. Incorrect: Presence of gram-positive cocci does not distinguish between the two, as both Staphylococcus aureus and Streptococcus pyogenes are gram-positive cocci. D. Correct: Production of catalase is a key distinguishing feature. Staphylococcus aureus is catalase-positive, whereas Streptococcus pyogenes is catalase-negative. This difference can be utilized to differentiate between these two bacteria in the clinical laboratory.

1. A patient presents with a malignant tumor derived from connective fibrous tissue. Which of the following describes most accurately this type of tumor? a. Adenoma b. Basal cell carcinoma c. Chondroma d. Fibrosarcoma e. Squamous cell carcinoma

Correct Answer: D Rationale: By definition, a fibrosarcoma is a malignant tumor derived from connective tissue. If the tumor were benign and derived from connective tissue, then it would be a fibroma. More context: A. Incorrect: An adenoma is a benign tumor that arises from glandular tissue, not from connective fibrous tissue. Glandular tissue consists of cells that produce and secrete substances such as hormones or mucus. B. Incorrect: Basal cell carcinoma is a type of skin cancer that arises from the basal cells of the epidermis. C.Incorrect: A chondroma is a benign tumor that originates from cartilage, which, although a type of connective tissue, does not align with the description of a malignant tumor originating from fibrous tissue. D. Fibrosarcoma: Fibrosarcoma is a malignant tumor that originates from fibrous connective tissue. Fibrous connective tissue provides structural support to various parts of the body, including tendons, ligaments, and fascia. This is the @ Correct Answer for a malignant tumor derived from connective fibrous tissue. E. Squamous cell carcinoma: Squamous cell carcinoma is a type of skin cancer that arises from squamous epithelial cells.

4. A 10-year-old male is diagnosed with chronic granulomatous disease (CGD). Which of the following conditions is the patient most likely to have developed prior to diagnosis? a. Jaundice due to hemolysis b. Malabsorption and steatorrhea (fat in stools) c. Megaloblastic anemia d. Recurrent infections with catalase-positive microorganisms

Correct Answer: D Rationale: CGD is a group of genetic disorders caused by loss-of-function mutations in any of the five subunits of the NADPH oxidase complex expressed in professional phagocytes (neutrophils and macrophages). Defective NADPH oxidase activity in these cells impairs their ability to kill microorganisms in phagosomes. In particular, defective NADPH oxidase enables persistent infection by catalase-positive microorganisms (bacteria or fungi). More Context: A. Incorrect: Jaundice due to hemolysis is not characteristically associated with chronic granulomatous disease (CGD). CGD primarily affects the immune system's ability to manage certain types of infections, specifically from catalase-positive bacteria and fungi, rather than directly affecting red blood cells. B. Incorrect: Malabsorption and steatorrhea (fat in stools) are generally not linked to CGD in a direct manner. CGD primarily impacts the immune system and its ability to manage particular infections, not predominantly influencing gastrointestinal absorption or fat metabolism. C. Incorrect: Megaloblastic anemia is not typically associated with CGD. The condition of CGD chiefly pertains to an impaired immune response to certain infections, and it doesn't directly involve pathways or mechanisms related to red blood cell development or vitamin B12/folate metabolism, which are pertinent to megaloblastic anemia. D. Correct: Individuals with CGD are notably susceptible to recurrent infections with catalase-positive microorganisms because the NADPH oxidase complex, crucial for the respiratory burst in phagocytes, is dysfunctional or absent. Catalase-positive bacteria and fungi can neutralize the hydrogen peroxide produced by phagocytes, and in the context of CGD, where the NADPH oxidase complex is impaired, the immune response is particularly compromised against these pathogens, making patients especially prone to recurrent infections with them.

14. A 28-year-old male comes to Urgent Care with fever, sore throat, and diarrhea for the past 5 days. He has faint, confluent erythematous macules on his trunk. These lesions are not itchy. The Urgent Care physician elicits a history of multiple unprotected sexual exposures over the past 6 months. Which of the following tests is most appropriate to diagnose this patient with acute HIV infection (acute retroviral syndrome)? A. CD4 T-cell count B. Confirmatory HIV antibody Western blot C. HIV screening ELISA for antibodies D. Quantitative real-time PCR for HIV RNA

Correct Answer: D Rationale: Detection of HIV RNA is the best way to diagnose acute HIV infection prior to the development of antibodies. The p24 antigen will rise quickly, but, if concerned for acute retroviral syndrome, one should make sure a PCR is ordered. Although CD4 count may be low, this would not be specific enough to diagnose HIV. More context: A. Incorrect: Although CD4 T-cell count can be affected by an acute HIV infection, using it as a diagnostic tool in this context is not specific enough because many conditions can lead to a decreased CD4 count. Furthermore, during the acute phase of an HIV infection, the CD4 count might not yet be significantly lowered. B. Incorrect: Western blot is typically used as a confirmatory test following a positive ELISA test for HIV antibodies. However, during the acute phase of HIV infection (acute retroviral syndrome), the body may not yet have produced sufficient antibodies to be detected by this test, thus it could yield a false-negative result. C. Incorrect: ELISA is often used as an initial screening test for chronic HIV infection by detecting antibodies. Similar to the Western blot, it may not be able to detect the infection in the acute phase because the body might not have produced detectable levels of antibodies yet, making the test potentially falsely negative in the early stages of infection. D. Correct: This test is considered the best choice for diagnosing an acute HIV infection. Quantitative real-time PCR for HIV RNA detects the virus itself (rather than the body's immune response to it) and can identify the infection before antibodies have formed or when the antibodies are not yet at detectable levels, which is the scenario in acute HIV infection or seroconversion illness. This makes it particularly useful in the context provided where the patient may be in the acute phase of infection given his symptoms and risk factors. In summary, when suspecting acute HIV infection as might be suggested by a high-risk exposure and a compatible clinical syndrome, it is imperative to directly detect the virus using RNA PCR since antibody production (and detection) might be delayed, making answer D the most appropriate choice in this context.

7. A patient with acute lymphoblastoid leukemia (ALL) is undergoing chemotherapy with various agents including methotrexate. After a high dose of methotrexate, the patient receives a dose of leucovorin (folinic acid). Which of the following statements best explains the rationale for administering leucovorin shortly after methotrexate? A. Leucovorin inhibits the intracellular enzyme, thymidylate synthase. B. Leucovorin requires reduction by dihydrofolate reductase for its pharmacodynamic effect. C. The combination increases potency of methotrexate activity within tumor cells. D. The combination minimizes bone marrow suppression.

Correct Answer: D Rationale: Leucovorin is converted to N5,N10-methylene-FH4, a downstream product of the reaction catalyzed by dihydrofolate reductase (DHFR), which is the target of inhibition by methotrexate. Therefore, leucovorin acts to bypass the methotrexate inhibited DHFR and provides an adequate supply of activated folate. Leucovorin enhances, not inhibits, the therapeutic effect and toxicity of 5-fluorouracil by increasing the binding of the drug to thymidylate synthase. Leucovorin is a folate derivative that does not need to undergo reduction by DHFR for utilization in various one-carbon transfer reactions. Leucovorin does not increase methotrexate potency. More context: A. Incorrect: This is not accurate because leucovorin doesn't inhibit thymidylate synthase; rather, it can enhance the effects of drugs like 5-FU that do inhibit this enzyme. But in the context of methotrexate therapy, its role is different - it helps healthy cells recover after methotrexate treatment without inhibiting this enzyme. B. Incorrect: Leucovorin doesn't need the enzyme dihydrofolate reductase (DHFR) to work. It's already in an active form and can be used by the body immediately, unlike other forms of folate. This is crucial when methotrexate, a DHFR inhibitor, is used in treatment. C. Incorrect: Actually, leucovorin does not increase the potency or effectiveness of methotrexate in killing cancer cells. Methotrexate and leucovorin act differently. Methotrexate inhibits an enzyme needed for cells to use folate, while leucovorin provides an active form of folate that bypasses this blockage. D. Correct: Methotrexate blocks a key enzyme (DHFR) to stop both cancerous and healthy cells from using folate, which they need to make DNA and multiply. Leucovorin offers a workaround for healthy cells, allowing them to use folate and make DNA even when methotrexate is trying to stop them. This combination allows us to target cancer cells while also protecting our healthy cells as much as possible.

20. You are evaluating an infant who has been diagnosed with oculocutanous albinism type 1 (OCA1) due to a homozygous loss-of-function mutation in the gene encoding tyrosinase, which is a key enzyme in the biosynthesis of melanin. The parents of the patient ask whether their child should minimize exposure to sunlight owing to their concerns for increased risk of developing skin cancer. Which of the following statements is the most accurate response to the parents? a. As long as the nucleotide excision repair (NER) machinery is functional, the child is not at increased risk of skin cancer and should enjoy as much sunlight as possible. b. It is always good to avoid sunlight but the child does not have any increased risk of skin cancer. c. The child has an increased risk of skin cancer but it is unrelated to UV exposure. d. The child should minimize sunlight exposure or use sunscreen when outdoors due to an increased risk of skin cancer.

Correct Answer: D Rationale: Melanin does protect skin cells from UV-induced DNA damage. While the NER mechanism may prevent some of that damage from turning into somatic mutations, in the absence of melanin the individual should minimize exposure, and/or use sunscreen on a regular basis, to avoid overwhelming the ability of the NER machinery to prevent accumulation of somatic mutations. More context: A. Incorrect: Although the nucleotide excision repair (NER) machinery does play a crucial role in repairing UV-induced DNA damage, the absence of melanin in individuals with oculocutanous albinism type 1 (OCA1) does indeed place them at an increased risk of skin cancer. Melanin is crucial for protecting skin cells from UV radiation, and even with functional NER machinery, the child is still at an elevated risk due to the lack of this protective pigment. B. Incorrect: The statement is partially incorrect. While minimizing sunlight exposure is generally good advice, the second part of the statement is inaccurate. The child does indeed have an increased risk of skin cancer, particularly due to the absence of melanin, which normally helps protect against UV-induced DNA damage. C. Incorrect: The child does have an increased risk of skin cancer and this risk is directly related to UV exposure. Melanin provides a protective mechanism against UV-induced DNA damage, and in its absence (such as in OCA1), there is an increased susceptibility to skin damage from UV light, thereby elevating the risk of skin cancer. D. Correct: Individuals with OCA1 have a deficiency in melanin production due to mutations in the tyrosinase gene, and melanin plays a critical role in protecting the skin from UV-induced damage. Therefore, individuals with OCA1 are indeed at an increased risk of developing skin cancer and should minimize sunlight exposure or use sunscreen to help protect their skin from UV damage. It is prudent to advocate for sun-protective measures, including minimizing direct sunlight exposure and using sunscreen, to reduce the risk of skin cancer.

1. The image shows the epidermis and portion of the dermis. The layer labeled: a. "W" is the stratum basale or basal layer b. "X" consists of metabolically active cells c. "Y" consists mostly of melanocytes d. "Z" consists mostly of stem cells

Correct Answer: D Rationale: N/A More Context: A. Incorrect: The stratum basale is the deepest layer of the epidermis and is characterized by a single layer of cuboidal to low columnar cells. However, as D is stated to be the @ Correct Answer, A cannot be correct in this context. B. Incorrect: The stratum corneum consists mainly of dead, flattened keratinocytes (corneocytes) with no nuclei, thus they are not metabolically active. This layer primarily serves as a barrier to protect the underlying tissue from infection, dehydration, chemicals, and mechanical stress. C. Incorrect: Melanocytes are found mostly in the stratum basale of the epidermis, where they produce melanin, a pigment that helps protect the skin from UV radiation D. Correct: The stratum basale is known for its population of epidermal stem cells, which divide to produce new keratinocytes, contributing to the continuous renewal of the epidermis. Without the ability to visualize the image, the accurate identification of the layers labeled "W", "X", "Y", and "Z" is not possible, which makes the comprehensive validation of the options challenging. However, given the specific correctness of option D provided in the premise, the rationale is provided accordingly. A: "W"is the dermal layer B:Stratum Corneum-Keratinocytes: Tough, dead cells with a waterproof barrier Desquamation occurs here at this layer; Desquamation is the natural shedding of dead skin cells from the stratum corneum, maintaining skin health. Scalded skin syndrome, caused by Staphylococcus aureus C:Not true because melanocytes are more where Z is, stratum basale. Y includes stratum spinosum... ○ Polyhedral Keratinocytes: ■ cells continue to divide and become spiky (NOTE: Polyhedral keratinocytes play a crucial role in maintaining the integrity of desmosome junctions in the epidermis. This shape allows them to closely pack together, maximizing the surface area of contact between adjacent cells. The irregular edges of polyhedral keratinocytes create numerous opportunities for desmosome attachment points.) ○ Langerhans cells: ○ immune cells that help protect the skin→ they move around ○ Squamous cell carcinoma found here!

11. A patient with severe left upper quadrant abdominal pain comes in after a recent motorcycle accident, and the Emergency Department physician suspects a ruptured spleen based on the pain and a rapidly falling hematocrit. An emergency blood transfusion is considered but the patient's blood type is not known. Which of the following donor blood types should be selected for this patient at this point? a. A b. B c. AB d. O

Correct Answer: D Rationale: Not considering the Rh antigen, blood type O (devoid of antigens A or B) is, of the four options listed, the blood type most compatible with all possible blood types (O, A, B or AB) of the patient to receive the blood transfusion. More Context: A. Incorrect: Selecting donor blood type A for this patient could be problematic if the patient's blood type is different (such as B or AB), as it may lead to an incompatible blood transfusion. This could result in a severe transfusion reaction and worsen the patient's condition. B. Incorrect: Similar to blood type A, selecting donor blood type B without knowing the patient's blood type can be risky, as it may not match the patient's blood type. This can lead to an incompatible transfusion and potential complications. C. Incorrect: Blood type AB individuals are often considered universal recipients, meaning they can receive blood from donors of any blood type (A, B, AB, or O) without causing a major transfusion reaction. However, since the patient's blood type is unknown, choosing blood type O as the donor blood type is a safe option because it can be transfused to the patient without knowing their blood type. D. Blood Type O: Blood type O is often considered the universal donor, as individuals with blood type O can donate blood to individuals with any blood type (A, B, AB, or O) without causing a major transfusion reaction. Therefore, when the patient's blood type is unknown, selecting donor blood type O is the safest choice to prevent an incompatible transfusion.

13. A 22-year-old male is struggling with taking his medications daily. Which of the following best describes the mechanism of action of a currently available antiretroviral therapy to which he may be at risk of developing resistance? A. Blockage of the CD4 co-receptor on T cells B. Disruption of protein synthesis via inhibition of translation C. .Inhibition of transcription of proviral DNA into mRNA D. Inhibition of viral cDNA synthesis by chain termination

Correct Answer: D Rationale: Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) inhibit viral cDNA synthesis by chain termination. All others are not mechanisms of action for the currently available HIV drugs. Intermittent adherence increases the risk of developing resistance. More context: A. Incorrect: While there are drugs that block CD4 co-receptor interaction (such as maraviroc, an entry inhibitor), resistance to these is not typically related to a patient's adherence to antiretroviral therapy (ART) but rather to the virus' tropism or use of alternative co-receptors. B. Incorrect: There aren't any antiretroviral drugs that primarily act by disrupting protein synthesis via inhibition of translation in the clinical use. C. Incorrect: While inhibiting transcription of proviral DNA into mRNA would theoretically inhibit HIV, this is not the primary action of currently used antiretroviral medications. D. Correct: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) function by inhibiting viral cDNA synthesis and inducing chain termination. Non-adherence to NRTIs can lead to viral resistance because, without consistent suppression of the virus, mutations may develop that confer resistance to these drugs. So, an irregular intake of medications could pave the way for resistant strains. HIV Antiretroviral Drug Classes we should know the mechanisms: 1. NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors) - Function: Bind to the active site of the reverse transcriptase enzyme. - Action: Inhibit viral replication by causing chain termination during the DNA synthesis phase. - Risks: Resistance may develop with incorrect use. 2. NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) - Function: Bind non-competitively to the reverse transcriptase enzyme. - Action: Alter the enzyme's conformation, making it non-functional in reverse transcription. 3. PIs (Protease Inhibitors) - Function: Inhibit the enzyme protease. - Action: Prevent the maturation of the virus by inhibiting the cleavage of proteins during viral assembly, notably affecting the creation of the viral capsid. 4. INSTIs (Integrase Strand Transfer Inhibitors) - Function: Block the enzyme integrase. - A

5. Which of the following antineoplastic agents can cause peripheral neuropathy by disrupting microtubule function in neurons? A. 5-Fluorouracil B. Methotrexate C. Nitrogen mustard D. Vincristine

Correct Answer: D Rationale: Of the antineoplastic agents listed as options in this question, only vincristine acts by disrupting microtubules in dividing cells (on-target effect) albeit also disrupting microtubules in axons, particularly in long nerves (off-target effect). More context: A. Incorrect: 5-Fluorouracil is an antimetabolite chemotherapy drug that primarily interferes with the synthesis of DNA and RNA. It does not disrupt microtubule function in neurons and is not associated with peripheral neuropathy. B. Incorrect: Methotrexate is another antimetabolite chemotherapy drug that inhibits the synthesis of DNA and RNA. It does not affect microtubules in neurons and is not a common cause of peripheral neuropathy. C. Incorrect: Nitrogen mustard agents, such as cyclophosphamide, are alkylating agents that primarily interfere with DNA structure and function. They do not disrupt microtubules and are not typically associated with peripheral neuropathy. D. Correct: Vincristine is a vinca alkaloid chemotherapy drug that disrupts microtubule function in neurons. This disruption of microtubules can lead to peripheral neuropathy, which is a well-known side effect of vincristine treatment. The drug's interference with microtubules impairs axonal transport in peripheral nerves, causing symptoms like numbness, tingling, and weakness in the extremities.

15. A patient previously had a severe allergic reaction to penicillin with Stevens-Johnson syndrome. Assuming that all of the following could treat streptococcal pharyngitis, which of the following drugs should be the next best choice for treatment of this patient? a. Ampicillin b. Ceftriaxone c. Cephalexin d. Clindamycin

Correct Answer: D Rationale: Stevens-Johnson syndrome is a severe, delayed hypersensitivity (type IV) reaction that would exclude subsequent use of any beta-lactam. Clindamycin does not have any cross reactivity with penicillin. More Context: A. Incorrect: Ampicillin is a penicillin antibiotic and should be avoided in patients with a history of a severe allergic reaction to penicillins, such as Stevens-Johnson syndrome, to prevent the risk of cross-reactivity and subsequent allergic reactions. B. Incorrect: Ceftriaxone is a cephalosporin antibiotic. Although the widely accepted practice is to avoid cephalosporins in patients with a history of severe penicillin allergy due to the potential risk of cross-reactivity between penicillins and cephalosporins, recent evidence suggests that the risk is significantly lower than previously thought. However, in a case of severe allergy like Stevens-Johnson syndrome, it would typically still be avoided as a precaution. C. Incorrect: Cephalexin, like ceftriaxone, is a cephalosporin and generally avoided in patients with a history of severe penicillin allergy due to potential for cross-reactivity, especially when the allergic reaction is severe as in Stevens-Johnson syndrome. D. Correct: Clindamycin is not a beta-lactam antibiotic and does not have cross-reactivity with penicillins. It is often used as an alternative in patients with penicillin allergies, making it a suitable choice in this scenario where the patient has a history of severe allergic reaction to a penicillin antibiotic.

4. The toxin secreted by a pathogenic microorganism, upon entry into intestinal epithelial cells, can hijack the signal transduction machinery of the host cell in such a way that triggers the opening of a chloride channel located on the apical membrane for relatively long periods of times. Which of the following is the most likely manifestation that a person infected by this microorganism may develop? a. Blood in stool b. Constipation c. Fatty diarrhea (steatorrhea) d. Watery diarrhea

Correct Answer: D Rationale: The molecular mechanism described in the question is most consistent with that by which pathogenic bacteria such as V. cholera cause secretory diarrhea. More Context: A. Incorrect: Bloody stool (hematochezia or melena) generally signifies an injury to the gastrointestinal tract, such as from invasive bacteria or physical injury, which isn't implied by the scenario involving the prolonged opening of a chloride channel. The toxin described doesn't indicate a mechanism leading to damage of blood vessels or tissues that would cause bleeding into the gastrointestinal tract. B. Incorrect: The opening of chloride channels on the apical membrane of intestinal epithelial cells typically leads to an efflux of chloride ions into the intestinal lumen. This usually draws water into the lumen through osmosis, increasing the fluid content of the stool and thereby promoting defecation. Thus, it would not lead to constipation but rather the opposite: diarrhea. C. Incorrect: Steatorrhea, or fatty diarrhea, typically arises from malabsorption of fats in the gastrointestinal tract, not from a toxin-induced ionic imbalance. Conditions like pancreatitis, celiac disease, or issues with bile secretion are more likely to cause this manifestation and are unrelated to the toxin mechanism described. D. Correct: When the chloride channel in intestinal epithelial cells is persistently open, chloride ions flow into the lumen of the intestine. Osmosis drives water to follow the ions to maintain isotonicity, increasing the water content in the intestinal lumen and resulting in watery diarrhea. This mechanism is indeed consistent with the mechanism of toxins produced by certain bacteria, such as Vibrio cholerae, leading to profuse, watery diarrhea by effectively "pulling" water into the intestinal tract.

5. A 25-year-old asymptomatic male has a complete blood count (CBC) performed for an insurance physical. The CBC shows normal white-blood cells and platelets, but hemoglobin is reduced at 9.7 mg/dL. Mean corpuscular volume (MCV) is 75 fL (normal 80-100), and mean corpuscular hemoglobin concentration (MCHC) is reduced at 28. He has no prior medical history, no history or evidence of bleeding and routine screening for gastrointestinal blood loss is negative. Three months of iron supplementation do not change his CBC panel. Which of the following statements is most likely to apply to this case? a. He carries biallelic loss-of-function mutations in the HBB gene causing beta-thalassemia major. b. He has abnormal absorption of iron due to the overproduction of hepcidin. c. He has abnormal absorption of vitamin B12 due to loss of gastric production of intrinsic factor. d. He is heterozygous for mutations in the HBB gene causing beta-thalassemia minor.

Correct Answer: D Rationale: This is most likely beta-thalassemia minor due heterozygous mutations in the HBB gene encoding beta-globin. These individuals often have mild microcytic anemia due to reduced beta-globin production. Beta-thalassemia major would cause much more severe, transfusion-dependent anemia early in life. There is no evidence for B12 deficiency, which causes macrocytosis, and no evidence for chronic inflammation leading to increased hepcidin production. More context: A. Incorrect: If the individual had biallelic loss-of-function mutations in the HBB gene, causing beta-thalassemia major, they would exhibit more severe symptoms much earlier in life. Beta-thalassemia major typically presents in infancy with severe anemia and is often transfusion-dependent, which is inconsistent with an asymptomatic 25-year-old. B. Incorrect: There is no given evidence to suggest that hepcidin overproduction and subsequent impaired iron absorption are occurring. Moreover, impaired iron absorption typically leads to an iron-deficiency anemia which should at least partially respond to iron supplementation, which is not the case here as per the provided scenario. C. Incorrect: A deficiency in vitamin B12 absorption, commonly due to a lack of intrinsic factor, typically leads to macrocytic anemia (MCV >100 fL) and not microcytic anemia (MCV <80 fL) as seen in this case. Thus, this option doesn't correlate with the patient's laboratory findings of an MCV of 75 fL. D. Correct: The patient being heterozygous for mutations in the HBB gene, causing beta-thalassemia minor, aligns with the presented case. Beta-thalassemia minor often manifests as a mild microcytic (low MCV), hypochromic (low MCHC) anemia, which aligns with the patient's lab results. Patients with beta-thalassemia minor can be asymptomatic and often do not show a response to iron supplementation, consistent with the given scenario.

17. A patient develops hives after receiving his second dose of cephalexin for an abscess on his leg. Which of the following describes most accurately the pathophysiology of his allergic reaction? a. Antigen-antibody complex deposition on vessel walls to activate complement b. Delayed CD8+ T-cell-mediated cytotoxicity triggered by antigen-presenting cells c. IgG deposition on the surface of red blood cells d. Mast cell degranulation following binding of IgE-drug complex to the Fc receptor

Correct Answer: D Rationale: This patient experienced a type-I hypersensitivity reaction upon his second exposure to cephalexin. This is an IgE-mediated reaction triggered by the binding of the allergen (in this case, the drug cephalexin) to IgE antibodies bound to the Fc receptors on the surface of mast cells, and occurs upon re-exposure in a previously sensitized individual. "IgG deposition on the surface of red blood cells" describes a type-II hypersensitivity reaction. "Antigen-antibody complex deposition on vessel walls to activate complement" describes a type-III hypersensitivity reaction. Finally, "delayed CD8+ T-cell-mediated cytotoxicity triggered by antigen-presenting cells" describes a type-IV hypersensitivity reaction. More Context: A. Incorrect: Antigen-antibody complex deposition on vessel walls to activate complement describes a Type III hypersensitivity reaction, which involves the formation and deposition of immune complexes, leading to complement activation and resulting in inflammation and tissue damage. This mechanism is not responsible for the immediate hypersensitivity reaction observed with hives (urticaria) following drug administration, which is typically a Type I hypersensitivity reaction. B. Incorrect: Delayed CD8+ T-cell-mediated cytotoxicity triggered by antigen-presenting cells refers to a Type IV hypersensitivity reaction, which is a delayed, T-cell mediated response and is not associated with the immediate allergic response (like hives) observed in the scenario, which is suggestive of a Type I hypersensitivity reaction. C. Incorrect: IgG deposition on the surface of red blood cells is indicative of a Type II hypersensitivity reaction, which involves antibody-mediated cellular dysfunction, cytotoxicity, or phagocytosis, and does not explain the immediate reaction (hives) following drug administration, which is characteristic of a Type I hypersensitivity reaction. D. Correct: Mast cell degranulation following binding of IgE-drug complex to the Fc receptor accurately describes a Type I hypersensitivity reaction. In this type of reaction, an allergen (here, cephalexin) binds to IgE antibodies that are bound to Fc receptors on mast cells, triggering the release of mediator

8. Which of the following describes most accurately the cells marked by the arrow in the image below? a. Endothelial cells b. Eosinophil c. Lymphocytes d. Mast cell e. Plasma cells

Correct Answer: E Rationale: The cells highlighted are plasma cells. Note the perinuclear hof, eccentric nucleus and the clockface appearance of the chromatin. Plasma cells can be seen in chronic inflammatory responses.

6. A patient comes to you with a boil (an infection in a hair follicle), and you suspect that this is due to Staphylococcus aureus infection. Histological examination of the image below (enlarged on the bottom), suggests that the majority of cells in the box are which of the following? a. Basophils b. Lymphocytes c. Macrophages d. Mast cells e. Neutrophils

Correct Answer: E Rationale: The cells shown on the image are neutrophils. They have a nucleus with anywhere between 2 and 5 lobes. They have a lightly stippled granular pink cytoplasmic appearance due to numerous small membrane-bound granules. More context: A. Incorrect: Basophils are a type of white blood cell involved in allergic reactions and inflammatory responses. They are relatively rare in the tissues and are not typically the predominant cell type in a bacterial infection like a boil caused by Staphylococcus aureus. Basophils are more commonly found in the bloodstream.Basophils release heparin (anticoagulant) and histamine (inflammation). B. Incorrect: Lymphocytes are immune cells involved in the adaptive immune response. While they can be present in tissues, they are not usually the predominant cell type during the initial stages of a bacterial infection. Lymphocytes are more associated with the later stages of the immune response. C. Incorrect: Macrophages: Macrophages are phagocytic immune cells that play a crucial role in ingesting and clearing pathogens, including bacteria like Staphylococcus aureus. However, in the early stages of infection, neutrophils are usually the first responders to bacterial invaders, followed by the recruitment of macrophages. So, while macrophages are important, they are typically seen later in the response. Monocytes become macrophages in the tissues. D. Incorrect: Mast cells are involved in allergic reactions and inflammatory responses, particularly those associated with allergies and asthma. They are not the primary immune cells that respond to bacterial infections like Staphylococcus aureus. E. Correct: Neutrophils are the most abundant type of white blood cells and are the first responders to bacterial infections. They are highly phagocytic and are known for their ability to engulf and destroy bacteria. In the context of a boil caused by Staphylococcus aureus, the presence of neutrophils is consistent with the early inflammatory response to a bacterial infection. Neutrophils can phagocyte and do respiratory/oxidative bursts (i.e. G6PD!)

20. A patient is diagnosed with cryptococcal meningitis. She is started on a medication that binds to ergosterol in the fungal cell wall. Which of the following medications is she most likely to have been prescribed? A. Amphotericin B B. Caspofungin C. Fluconazole D. Terbinafine

Correct Answer: A Rationale: Amphotericin B binds to ergosterol (a fungal counterpart of the cholesterol in humans) causing pores in the membrane that result in rapid cell lysis. Amphotericin is part of the induction therapy used for cryptococcal meningitis. More context: A. Correct: Amphotericin B sticks to a component (ergosterol) in the fungus cell, makes holes in it, and kills the cell. This medicine is often used to start treatment for cryptococcal meningitis because it can effectively kill the fungus and reach the brain and spinal cord. B. Incorrect: Caspofungin doesn't stick to ergosterol. It works by interfering with how the fungus builds its cell wall, but not in the way described in the question. It's also not the first choice for treating this type of meningitis. C. Incorrect: Fluconazole is used in treating cryptococcal meningitis, but not in the way mentioned in the question. It doesn't stick to ergosterol but blocks a step in making it. It's usually used later in treatment, not at the start. D. Incorrect: Terbinafine stops the fungus from making ergosterol but doesn't stick to it directly. Plus, it's usually not used for treating cryptococcal meningitis but rather fungal infections of skin, hair, or nails.

17. A 45-year-old male underwent bone marrow transplantation for acute myelogenous leukemia (AML). Two months after the transplant, he has fever and cough, and remains persistently neutropenic. A CT scan of the lungs shows a focal nodular lesion. Needle biopsy is done that shows septate hyphae with a 45-degree-angle branching pattern. Which of the following pathogen is most likely to be causing his illness? A. Aspergillus fumigatus B. Candida albicans C. Histoplasma capsulatum D. Pneumocystis jiroveci (carinii)

Correct Answer: A Rationale: Aspergillus fumigatus is a leading cause of invasive fungal infections in patients with neutropenia. It is the only septate mold in this list. Candida is a yeast, and Histoplasma appears as yeast in tissue (37ºC). Pneumocystis jiroveci pneumonia would not present as a focal nodular lesion. More context: A. Correct: This fungus (Aspergillus fumigatus) is a common cause of infection in people who have low levels of neutrophils (a type of white blood cell), like our patient. The key clue is in the biopsy finding: the fungus has branches at 45-degree angles, which is typical of *Aspergillus*. Plus, this fungus can create a lump, or nodule, in the lungs, just like what's seen on the CT scan. B. Incorrect: While Candida can indeed infect people with weakened immune systems, it's a yeast, not a mold, and it doesn't form the 45-degree-angle branches in its hyphae (the fungus fibers) like what was found in the biopsy. So it's not what we're looking for. C. Incorrect: This fungus tends to show up as yeast at body temperature (like in our patient), not as the branching mold that was found. So it's not a match for what we're seeing in the biopsy. D. Incorrect: This organism might be considered in someone with a weakened immune system who has lung symptoms. However, Pneumocystis pneumonia doesn't typically create a single lump or nodule in the lung as seen in the CT scan, so it's not our answer.

23. The aspirate from an intraabdominal abscess in your patient grows multiple organisms. The patient is currently on ceftriaxone and metronidazole. Which one of the following organisms causing this patient's infection is being targeted by metronidazole? a. Bacteroides fragilis b. Escherichia coli c. Proteus mirabilis d. Pseudomonas

Correct Answer: A Rationale: Bacteroides fragilis is a gram-negative rod and an obligate anaerobe. Metronidazole is active against gram-negative obligate anaerobes only; hence it is active against Bacteroides fragilis alone in this patient. Escherichia coli, Proteus mirabilis, and Pseudomonas spp are all gram-negative rods but not obligate anaerobes; these other organisms are being targeted by ceftriaxone. More context: A. Correct: Bacteroides fragilis is an obligate anaerobe, and metronidazole is well-known for its activity against anaerobic bacteria. Therefore, in the context of the given patient scenario, metronidazole is being used to target B. fragilis. B. Incorrect: Escherichia coli is a facultative anaerobe and typically NOT the primary target for metronidazole. In the therapeutic context provided, ceftriaxone, being a broad-spectrum cephalosporin antibiotic, would be the agent targeting E. coli. C. Incorrect: Proteus mirabilis is not typically targeted by metronidazole as it is NOT an obligate anaerobe. Ceftriaxone would be more apt at targeting P. mirabilis due to its broad-spectrum activity against many Gram-negative organisms. D. Incorrect: Pseudomonas spp. are not effectively targeted by metronidazole. Pseudomonas, being a Gram-negative aerobic rod, is also NOT an obligate anaerobe and thus, metronidazole is not the antibiotic of choice for infections caused by Pseudomonas. Ceftriaxone also generally has poor activity against Pseudomonas, and alternative antipseudomonal agents would usually be selected for treating infections involving this organism.

12. A patient is found to have thrombocytopenia (abnormally decreased number of platelets in the blood). Which of the following is most likely to develop in such a patient? a. Bleeding from mucosal membranes b. Deep vein thrombosis c. Large bleeds into joints d. Re-bleeding after initial clot formation

Correct Answer: A Rationale: Bleeding from mucosal membranes is a common symptom in individuals with abnormally low platelet counts. Large bleeds into joints are typical of hemophilia. Increased clotting would be expected in, for example, deficiencies in protein C or protein S. More Context: A. Correct: Thrombocytopenia is characterized by a low platelet count, leading to an increased risk of bleeding from mucosal surfaces like the gums, nose, gastrointestinal tract, and urinary tract. B. Incorrect: Deep vein thrombosis (DVT) is primarily associated with hypercoagulable states, not thrombocytopenia. DVT often involves clotting protein deficiencies, such as protein C and protein S deficiencies, which promote excessive clot formation. C. Incorrect: Large bleeds into joints are typical of hemophilia, a clotting factor disorder, not thrombocytopenia, which primarily affects platelet counts. D. Incorrect: Re-bleeding after initial clot formation is not a common consequence of thrombocytopenia but may occur in disorders involving clotting factors or fibrinogen deficiencies, unrelated to thrombocytopenia.

5. The local Public Health agency investigated a food-borne outbreak of watery diarrhea. Culture of some patients' stool grew a curved gram-negative rod. One of these patients also developed the rare complication of an ascending paralysis. Which of the following is the most likely pathogen? a. Campylobacter jejuni b. Escherichia coli c. Klebsiella pneumoniae d. Salmonella typhi

Correct Answer: A Rationale: Campylobacter is the only curved gram-negative rod on the list that would produce an outbreak of watery diarrhea associated with food and can also cause Guillain-Barre through a process known as molecular mimicry. More context: A. Correct: Campylobacter jejuni fits the description as it is a curved, gram-negative rod and is one of the most common bacterial causes of diarrhea worldwide. Additionally, Campylobacter jejuni has been associated with the development of Guillain-Barré syndrome (GBS), a neurological disorder that involves ascending paralysis. GBS is thought to develop due to a process called molecular mimicry, where the immune system attacks the nerves, mistaking them for the pathogen. B. Incorrect: While Escherichia coli can indeed cause outbreaks of watery diarrhea, it is not a curved rod but a straight rod-shaped bacterium. E. coli is also not typically associated with the development of Guillain-Barré syndrome, thus not fitting the complete clinical picture provided in the question. C. Incorrect: Klebsiella pneumoniae is a gram-negative rod but it is not typically associated with foodborne outbreaks of watery diarrhea or the development of Guillain-Barré syndrome. Moreover, it is not a curved rod, another point making it an unlikely suspect based on the given description. D. Incorrect: Although Salmonella typhi can be associated with outbreaks and cause diarrhea, it is not a curved rod and is not associated with Guillain-Barré syndrome. Additionally, the type of diarrhea and systemic illness (typhoid fever) caused by S. typhi is clinically distinct from the scenario described.

19. A patient with acute myeloid leukemia develops neutropenia while on chemotherapy. She subsequently has a fever to 101.3°F (38.5°C). She has no other focal symptoms (i.e., no cough, no abdominal pain, and no pain on urination). Which of the following regimens should you start her on right away? a. A broad-spectrum antibacterial antibiotic b. An antifungal medication c. An antiparasitic medication d. An antiviral drug

Correct Answer: A Rationale: In patients with neutropenia, the leading cause of fevers is a bacterial infection. In most cases, we will prescribe an anti-pseudomonal beta-lactam such as cefepime (4th generation cephalosporin). Fungal infections also may occur in neutropenia but are only typically considered if a patient is not responding to antibiotics. More Context: A. Correct: In patients with neutropenia (especially from chemotherapy), there is a significant risk for bacterial infection due to the suppressed immune system. Fever can be a solitary sign of a bacterial infection in neutropenic patients. The immediate initiation of broad-spectrum antibacterial therapy is standard practice to quickly tackle potential bacterial pathogens and reduce associated morbidity and mortality. B. Incorrect: While fungal infections can occur in neutropenic patients, especially after prolonged periods of neutropenia or antibiotic use, the initial empirical therapy in a febrile neutropenic patient typically targets bacterial pathogens due to their rapid onset and potential for rapid progression. C. Incorrect: Parasitic infections are generally not the immediate concern in febrile neutropenic patients without specific epidemiologic or clinical indications. Thus, starting an antiparasitic medication as the initial treatment would not be in line with standard protocols. D. Incorrect: While viral infections can occur in neutropenic patients, bacterial infections are more common and tend to progress more rapidly and are, therefore, the initial focus of empirical therapy in this setting. Antiviral drugs might be considered later depending on the clinical course, exposure history, and additional laboratory information.

19. Your healthcare team has been providing care to several members of a multigenerational family with a significant history of melanoma. From the analysis of the family pedigree, an autosomal-dominant mode of inheritance seems most likely. DNA analysis reveals in affected family members a germline loss-of-function mutation in the CDKN2A gene, which the literature describes as "a tumor-suppressor gene." If tumor-suppressor genes linked to autosomal chromosomes typically require loss of function of both gene copies in order to drive cell transformation, why is the likely mode of inheritance observed in the family autosomal dominant and not autosomal recessive? a. Affected family members have inherited one mutant allele but will not develop melanoma until a somatic mutation affects the function of the second copy of the gene. b. Analysis of the family pedigree is likely wrong because familial forms of melanoma due to mutations in CDKN2A follow an autosomal-recessive pattern. c. DNA analysis is likely wrong because no germline mutations are observed in cases of melanoma involving CDKN2A mutations. d. Further DNA analysis will likely show that family members heterozygous for the inher

Correct Answer: A Rationale: Inheriting a single loss-of-function mutation in CDKN2A increases the lifetime risk of developing melanoma (and other forms of cancer) several fold because, even when cells carrying one normal copy of CDKN2A remain untransformed, any cell of the body that is affected by a somatic mutation involving the only functional copy will be left devoid of the normal tumor suppressor activity of the gene and, consequently, develop a transformed phenotype. Remember, oncogene: need 1 mutation and Tumor suppressor gene need 2! More context: A. Correct: This statement accurately describes the "two-hit hypothesis," which postulates that individuals who inherit one defective copy of a tumor-suppressor gene (first "hit") are predisposed to cancer, but will not actually develop cancer until the second, normal copy of the gene also becomes mutated (second "hit"). Therefore, affected family members have inherited one mutant allele (autosomal-dominant inheritance) but will not develop melanoma until a somatic mutation affects the function of the second copy of the gene. B. Incorrect: Familial forms of melanoma due to mutations in CDKN2A do not necessarily follow an autosomal-recessive pattern. Indeed, in most cases involving tumor-suppressor genes like CDKN2A, the pattern of inheritance observed is autosomal dominant, because inheriting one mutated allele is sufficient to increase the risk of cancer, even though a second, somatic mutation is usually required for cancer to actually develop. C. Incorrect: Germline mutations in CDKN2A are indeed observed in some familial cases of melanoma. The CDKN2A gene, located on chromosome 9p21, encodes two unrelated proteins, p16INK4 and p14ARF, which play crucial roles in controlling the cell cycle and, therefore, suppressing tumor development. D. Incorrect: Further DNA analysis is not likely to show that heterozygous family members are unaffected healthy carriers. Carriers of a mutant allele of a tumor-suppressor gene, even in a heterozygous state, typically show an increased risk of developing cancer, in line with the aforementioned "two-hit hypothesis." This is characteristic of an autosomal dominant pattern of inheritance.

1. A 15-year-old female presents to the clinic with a chief complaint of diarrhea, reported as consisting of about 4-6 loose stools per day. Which of the following additional information would make a pathogenic bacterial infection least likely in your differential diagnosis? a. Diarrhea began four weeks ago-in b. Diffuse abdominal pain c. Presence of fever d. Significant dehydration

Correct Answer: A Rationale: Most cases of diarrhea caused by pathogenic bacterial infection are expected to resolve within two weeks. Although four weeks (28 days) do not formally rule out a bacterial pathogen, other possible causes should be given more consideration. More context: A. Correct: Diarrhea caused by pathogenic bacteria is often of an acute nature, commonly resolving within a few days to two weeks. A duration of four weeks (which falls into the category of persistent diarrhea) may suggest other possible etiologies, such as inflammatory bowel diseases, irritable bowel syndrome, or perhaps a non-infectious cause. Therefore, a bacterial pathogen as the sole or primary cause becomes less likely, though not impossible, and other causes should be explored. B. Incorrect: Diffuse abdominal pain can be associated with various causes of diarrhea, including bacterial infections. It doesn't necessarily make bacterial infection less likely since pain can result from the irritation of the intestinal lining, increased intestinal motility, or inflammation - all possible consequences of a bacterial infection. C. Incorrect: Fever is a common symptom associated with infections, including those caused by pathogenic bacteria. A fever signals that the body is responding to an infection or some form of inflammation, so its presence might make a healthcare provider more suspicious of an infectious cause for the diarrhea. D. Incorrect: Significant dehydration may suggest that the diarrhea is severe and could be caused by a pathogenic organism capable of inducing substantial fluid and electrolyte loss (like in cholera). Therefore, dehydration would not make a bacterial cause less likely, and in some cases, might even increase the suspicion, depending on the clinical context.

5. This image shows a neoplastic (cancerous) disruption involving the most prevalent type of cell in the deepest layer of the epidermis. The diagnosis is: a. Basal cell carcinoma b. Melanoma c. Merkel cell carcinoma d. Squamous cell carcinoma

Correct Answer: A Rationale: N/A More Context: A. Correct: Basal cell carcinoma originates from the basal cells, which are located in the deepest layer of the epidermis, the stratum basale. It is the most common type of skin cancer. The stratum basale predominantly contains basal keratinocytes, and these cells are indeed the most prevalent type in this layer. Thus, a neoplastic disruption in this area, involving the most prevalent type of cell, would suggest basal cell carcinoma, aligning with the information given in the question. B. Incorrect: While melanoma does originate from melanocytes, which are also located in the stratum basale of the epidermis, melanocytes are not the most prevalent type of cell in this layer. Basal keratinocytes are far more numerous. Therefore, if the disruption involves the most prevalent type of cell in the deepest layer, it is not likely to be melanoma based on the provided information. C. Incorrect: Merkel cell carcinoma arises from Merkel cells, which are indeed found in the stratum basale of the epidermis and are involved with sensory perception (touch). However, like melanocytes, Merkel cells are not the most prevalent type of cell in the basal layer of the epidermis, making this choice incongruent with the details provided in the question. D. Incorrect: Squamous cell carcinoma originates from squamous cells, not from the basal cells found in the deepest layer of the epidermis. Squamous cells are more superficially located in the epidermis, primarily in the stratum spinosum, although they are also found throughout the other layers as cells differentiate and move upwards. Therefore, this option does not align with the disruption in the deepest layer of the epidermis.

2. The basement membrane is a histological structure with important clinical implications. What statement characterizes the basement membrane (BM)? a. The BM is a structure between the epithelium and underlying connective tissue b. The BM does not allow nerves through in order to protect the overlying epithelium c. The BM is a cellular structure capable of regenerating itself d. The BM is pierced by blood vessels that serve the cells of the overlying epithelium

Correct Answer: A Rationale: N/A More Context: A. Correct: The basement membrane (BM) is a histological structure that separates the epithelium (e.g., the lining of organs or tissues) from the underlying connective tissue. It provides structural support and helps anchor the epithelial cells. B. Incorrect: The basement membrane's primary function is to provide a barrier and structural support, primarily for the separation of epithelium and connective tissue. While it does play a role in protecting the epithelium, it is not specifically designed to block nerves from passing through. C. Incorrect: The basement membrane is not a cellular structure. It is primarily composed of extracellular matrix components like collagen, laminin, and proteoglycans. It does not have the ability to regenerate itself in the same way that living tissues with cells can. D. Incorrect: The basement membrane is relatively avascular, meaning it does not have a network of blood vessels running through it. It acts as a barrier and does not serve as a conduit for blood vessels. Blood vessels typically reside in the underlying connective tissue, not within the basement membrane itself.

3. What statement is true about Langerhans cells and related facts? a. Langerhans cells phagocytize foreign antigens, travel through the lymphatic system to a lymph node, and initiate an immune response there b. Langerhans cells are epithelial cells in the epidermis and they are anchored to adjacent cells by desmosomes, as clearly visible in the image c. Langerhans cells are generated in the skin, as a result of basal cell mitotic division d. They are found most clearly in the stratum corneum of the epidermis, although they can also be found less frequently in the stratum granulosum

Correct Answer: A Rationale: N/A More context: A. Correct: Langerhans cells are indeed a type of dendritic cell found in the epidermis, and they play a key role in the skin's immune responses. They can phagocytize pathogens or other foreign materials, and subsequently travel to lymph nodes. In the lymph nodes, Langerhans cells present antigens to T cells, thus initiating an adaptive immune response. Therefore, this statement aligns with known functions of Langerhans cells and is correct as indicated. B. Incorrect: Langerhans cells are not epithelial cells but are immune cells (a type of dendritic cell) in the epidermis. While they are located in the epidermis, their primary function is related to immune surveillance and response rather than maintaining the structural integrity of the tissue, which is a characteristic function of epithelial cells. C. Incorrect: Langerhans cells are not generated through mitotic division of basal cells in the skin. They are derived from bone marrow precursors, which travel to the skin and differentiate into Langerhans cells. The mitotic division of basal cells in the skin primarily gives rise to keratinocytes, which move upwards through the epidermal layers and differentiate accordingly. D. Incorrect: Langerhans cells are predominantly found in the stratum spinosum, not in the stratum corneum. The stratum corneum is primarily composed of dead, anucleated keratinocytes (corneocytes) and does not contain Langerhans cells. Langerhans cells reside in the stratum spinosum where they can effectively survey the epidermis and interact with other cells to initiate immune responses.

6. Which of the following conditions is mostly associated with a phototoxic reaction that can occur in any patient who receives sufficient quantities of a photosensitive drug and is exposed to enough light? a. It can develop on first exposure b. It involves cell-mediated hypersensitivity c. It is a consequence of overuse of SPF 30 sunscreen d. It requires sensitization

Correct Answer: A Rationale: Photosensitive adverse events are usually categorized as either phototoxic or photoallergic, and additionally as either topical or systemic. Phototoxic reactions have a higher incidence than photoallergic reactions and can theoretically occur in any individual exposed to the respective agent and radiation, if the dose of either of the two involved factors exceeds a critical threshold. Phototoxic reactions are a dose-dependent phenomenon with respect to both the drug and light exposure. Photoallergic reactions are less common than phototoxic reactions and result from cell-mediated immunity; like other allergic reactions, they do not develop on first exposure and, thus, require sensitization. Liberal use of sunscreen is recommended - the more the better, using the 'teaspoon rule'. More context: A. Correct: Phototoxic reactions can indeed develop upon first exposure to a photosensitizing agent and light. It is not an allergic reaction, so it doesn't require previous exposure to occur. If a person takes a drug that is photosensitizing and is exposed to sufficient light (especially UV light), a phototoxic reaction can occur regardless of whether they have been exposed to the drug before. B. Incorrect: Cell-mediated hypersensitivity (type IV) is a feature of photoallergic reactions, not phototoxic reactions. Photoallergic reactions require sensitization and involve the immune system, typically manifesting in a delayed manner after exposure to the photosensitizing agent and light. C. Incorrect: Overuse of sunscreen would not be associated with phototoxic reactions. In fact, liberal use of sunscreen is generally recommended to prevent UV light-associated skin damage and does not induce phototoxic reactions. Sunscreens, especially those with a higher Sun Protection Factor (SPF), are designed to protect skin from the harmful effects of UV light. D. Incorrect: The requirement for sensitization pertains to photoallergic reactions, not phototoxic ones. Photoallergic reactions involve an immune response, and thus, require an initial exposure to the agent to sensitize the immune system. Phototoxic reactions, on the other hand, do not involve the immune system and can occur upon first

3. A patient with a genetic defect in an enzyme of the pentose phosphate pathway (PPP) develops hemolytic anemia following the ingestion of a salad containing fava beans. Which of the following is the most likely mechanism linking food intake with the PPP to explain the presentation of widespread destruction of red blood cells (RBCs)? a. Fava beans contain chemicals that trigger production of hydrogen peroxide, and RBCs need NADPH generated by the PPP to eliminate it and prevent cell death. b. Fava beans contain large quantities of ribose, which the PPP can metabolize to prevent its inhibition of the Na+/K+-ATPase. c. RBCs use PPP as the sole source of ATP production, which is required for viability. d. The event of hemolytic anemia was due to defective PPP but unrelated to the ingestion of fava beans.

Correct Answer: A Rationale: RBCs uses an enzymatic system for elimination of hydrogen peroxide that relies on glutathione in reduced form. The PPP is the only pathway that mature RBCs have to generate NADPH, which is required by the above-mentioned enzymatic system to regenerate glutathione in reduced form. This patient most likely has glucose-6-phosphate dehydrogenase (G6PD) deficiency. More context: A. Correct: Fava beans contain vicine and convicine, which can generate reactive oxygen species (such as hydrogen peroxide) within the red blood cells (RBCs) upon metabolism. NADPH, generated by the PPP, specifically via the glucose-6-phosphate dehydrogenase (G6PD) enzyme, is crucial to help RBCs mitigate oxidative stress by maintaining the reduced form of glutathione which neutralizes hydrogen peroxide. If there is a deficiency in an enzyme of the PPP (such as G6PD), the RBCs would be less capable of dealing with the oxidative stress, leading to hemolysis. B. Incorrect: While ribose is indeed a sugar, and it is related to the pentose phosphate pathway, the statement that fava beans contain large quantities of ribose that can inhibit the Na+/K+-ATPase is not accurate. Furthermore, the idea that the PPP metabolizes ribose to prevent this is not established in scientific literature and does not directly relate to the observed hemolytic anemia in the context provided. C. Incorrect: While the PPP is important for RBCs, it is not utilized as the sole source of ATP production; glycolysis serves as a major pathway for ATP production in RBCs. The PPP is vital for the production of NADPH, which helps in neutralizing reactive oxygen species and thus, preventing oxidative damage. D. Incorrect: There is a well-established link between the ingestion of fava beans and hemolytic anemia in individuals with G6PD deficiency, a condition that affects the PPP. Thus, the statement that the event of hemolytic anemia is unrelated to the ingestion of fava beans is not accurate in the context of the described scenario. Why do fava beans trigger G6PD? Fava beans contain the compounds vicine and convicine. These chemicals are metabolized to divicine and isouramil, which are potent oxidizing agents. In persons with glucose-6-ph

8. You suspect that a patient recently admitted to the hospital may be suffering from hemolytic anemia. Assuming that you are correct, which of the following findings will be least likely in this patient? a. Decreased reticulocyte count b. Increased indirect (unconjugated) bilirubin c. Increased urine and fecal urobilinogen d. Marrow erythroid hyperplasia

Correct Answer: A Rationale: Reticulocytes ("Retics") [baby RBC; no nucleus = measure BM response] should be increased in hemolysis due to the bone marrow trying to replace the hemolyzed red blood cells. More context: A. Correct: Decreased reticulocyte count is the least likely finding in a patient with hemolytic anemia. Hemolytic anemia is characterized by the premature destruction of red blood cells (RBCs), and the bone marrow responds to this by increasing the production of new RBCs, which would be reflected as an increase, not a decrease, in the reticulocyte count. Reticulocytes are immature RBCs, and their count would typically rise in the setting of hemolytic anemia as the body attempts to compensate for the lost cells by producing more new cells. B. Incorrect: Increased indirect (unconjugated) bilirubin is likely in hemolytic anemia. Hemolysis, or the destruction of RBCs, releases hemoglobin, which is then broken down into biliverdin and converted to unconjugated bilirubin. This form of bilirubin is taken to the liver, and if the liver cannot process it fast enough due to the increased load from the hemolysis, it will accumulate in the blood, leading to increased indirect bilirubin. C. Incorrect: Increased urine and fecal urobilinogen is also likely in hemolytic anemia. With RBC destruction, there is an increase in the production of bilirubin. Some of this bilirubin is converted into urobilinogen by bacteria in the gut and can be reabsorbed and excreted in the urine or excreted in the feces. When hemolysis is increased, there is more bilirubin available to be converted into urobilinogen, hence it is likely to be found in increased amounts in the urine and feces. D. Incorrect: Marrow erythroid hyperplasia is also likely to be found in hemolytic anemia. In response to the increased destruction of RBCs, the bone marrow enhances the production of RBCs, resulting in erythroid hyperplasia. This is a compensatory mechanism aimed at replacing the lost RBCs and is typically observable in the marrow in hemolytic conditions. As the bone marrow undergoes erythroid hyperplasia, bones expand in an attempt to create more space for increased red blood cell production. This process typically initiates in the

14. The carrier frequency of loss-of-function alleles in a gene linked to an autosomal recessive disease in 1% in population A and 2% in population B. Which of the following is the best estimate of the risk of a baby born to an unaffected member of population A and an unaffected member of population B to develop the disease? a. ~1/20,000 b. ~1/10,000 c. ~1/4000 d. ~3%

Correct Answer: A Rationale: The probability of the baby being affected is: 1% x 1/2 x 2% x 1/2 = 1/100 x 1/2 x 2/100 x 1/2 = 1/20,000. More context: Given: - Carrier frequency in population A = 1% = 1/100 - Carrier frequency in population B = 2% = 2/100 1. **Calculate the probability of each parent being a carrier and passing the allele to the child**: - Member A passing the allele: (Carrier frequency A) x (Probability of passing the allele) = (1/100) x (1/2) - Member B passing the allele: (Carrier frequency B) x (Probability of passing the allele) = (2/100) x (1/2) 2. **Calculate the probability of the child receiving both alleles (one from each parent) and thus having the disease**: - Probability (A passing allele and B passing allele) = (Probability A passes allele) x (Probability B passes allele) - = [(1/100) x (1/2)] x [(2/100) x (1/2)] - = (1/200) x (1/100) - = 1/20,000

17. A 20-year-old female who is at your office for a regular health checkup reports to you that her younger brother has been diagnosed with a rare autosomal-recessive disease. Even when she is not yet planning to have kids, she wonders about her risk of carrying "the gene" (mutation). Provided that you can exclude the possibility of her developing the same disease later in life, which of the following will be the best estimate for her risk of being a carrier? a. ½ b. ⅔ c. ¾ d. ~1

Correct Answer: B Rationale: Based on the assumption of the 20-year-old female being unaffected while having an affected sibling, her risk of being a carrier is 2 out of 3 equally likely scenarios, or 2/3. More context: Let's consider the possible scenarios for the 20-year-old female's genotype: Scenario 1: She inherited one normal gene from one parent and one mutated gene from the other parent. In this case, she would be a carrier of the mutation. Scenario 2: She inherited two normal genes, one from each parent. In this case, she would NOT be a carrier. Scenario 3: She inherited two mutated genes, one from each parent. This scenario is highly unlikely given that she is not affected by the disease, but the question assumes that she won't develop the disease later in life anyway. So, there are three possible scenarios for her genotype, and two of them (scenario 1 and scenario 2) result in her being a carrier, while one (scenario 3) does not. These scenarios are equally likely, so the probability of her being a carrier is 2 out of 3 equally likely scenarios, which is 2/3.

11. A couple seeks genetic counseling to lea rn whether their unborn child, determined to be XY through prenatal testing, could develop glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder. The father-to-be is affected, and the mother-to-be is descent from a population in which the mutant allele frequency has been estimated at ~2.5%. What is the best estimate of the risk for the unborn child? a. ~1.25% b. ~2.5% c. ~5% d. ~⅔

Correct Answer: B Rationale: Given the knowledge about the unborn child being XY, the risk of an X-linked disease can be calculated as one half of the probability of the mother-to-be being a carrier, or 1/2 x 2q = q ~ 2.5%. Notice that the information about the disease status of the father-to-be is irrelevant, because the XY unborn child inherited the X chromosome from the mother-to-be and the Y chromosome from the father-to-be. More Context: Chance of mother being a carrier (2pq): 2 x 1 x .025%= 5% She has ½ chance of passing on the affected allele, so ½ x 5%= 2.5%

12. A child is found to suffer from non-infectious diarrhea due a rare genetic condition caused by biallelic loss-of-function mutations in the gene encoding SGLT1. Which of the following should be considered as the best course of action to manage the child's gastrointestinal symptoms? a. Fecal transplantation b. Low-carbohydrate diet c. Oral rehydration therapy (ORT) d. Oral supplementation of pancreatic enzymes

Correct Answer: B Rationale: SGLT1 is a sodium/glucose co-transporter primarily responsible for the uptake of glucose and galactose (driven by the Na+ gradient established by the Na+/K+-ATPase) into epithelial cells of the small intestine. Unfortunately, the vast majority of carbohydrates in our diet yield glucose, and lactose in milk and derivatives yields both glucose and galactose. Of the list of four options, only a strict diet trying to avoid these carbohydrates seems reasonable. More context: A. Incorrect: Fecal transplantation is primarily utilized to manage certain infections of the gut, such as recurrent C.diff infection, by helping to re-establish a healthy gut microbiome. It is not targeted towards managing symptoms arising due to genetic conditions affecting nutrient transport, like mutations in SGLT1, and therefore would likely not address the underlying issue of glucose and galactose malabsorption in this case. B. Correct: The SGLT1 transporter plays a crucial role in the absorption of glucose and galactose in the small intestine. Therefore, if it is not functioning properly due to genetic mutations, minimizing intake of carbohydrates, especially those that yield glucose and galactose upon digestion, could help reduce symptoms related to their malabsorption, such as diarrhea. A low-carbohydrate diet could potentially minimize the amount of unabsorbed sugars in the gut, thereby managing gastrointestinal symptoms. C. Incorrect: ORT is pivotal in managing and preventing dehydration due to diarrhea, which is a crucial supportive management step. However, while it addresses a consequential symptom (dehydration), it doesn't directly target the underlying cause of the diarrhea in this case, which is the malabsorption of glucose and galactose due to defective SGLT1. It is a supportive measure but may not be the best initial step to manage the underlying issue in this case. D. Incorrect: Pancreatic enzyme supplementation aids in the digestion of fats, proteins, and carbohydrates by providing enzymes that may be deficient, such as in conditions like cystic fibrosis. However, in the context of SGLT1-related malabsorption, where the issue lies in the transport of monosaccharides across the intestin

16. The biological father of a child affected with an autosomal-recessive disease remarries with the member of a population for which the reported incidence of the same monogenic disease is about 1 in 40,000. Should they decide to have children, which of the following will be the best estimate of the risk of a child from this new couple to suffer from the same disease? a. ~1/300 b. ~1/400 c. ~1/600 d. ~1/800

Correct Answer: B Rationale: The probability of the biological father of the affected child being a carrier is ~1 (i.e., he is a so-called 'obligate carrier'). The probability of his new partner to being a carrier is ~2/√(40,000), or ~1/100. Hence, the risk of a new child from these two parents to develop the disease is ~1 x 1/2 x ~1/100 x 1/2, or ~1/400. More context: Dad is suspected to be a carrier for the disease, so he has a 50%, or ½ chance of giving the allele to the new child. The new mom is from a population with a frequency of disease of 1/40,000 (q2), so we need to calculate the p, and then she has a 50% chance of giving the p to the new child so we get... Dad: 1 x ½ Mom: 1/100 x ½ Dad x Mom= (1 x ½ ) x (1/100 x ½ )= 1/400

9. Based on what you know about granulomas, which of the following describes most accurately the cells demarcated by the box? a. Epithelial cells b. Giant cells c. Lymphocytes d. Mast cells e. Plasma cells

Correct Answer: B Rationale: These are giant cells. They are fused macrophages that form a multi-nucleated "giant" cell. Note the peripherally arranged nuclei in giant cells. They are seen in caseating granulomas. More context: A. Incorrect: Epithelial cells are a type of tissue cell that lines the surfaces of organs and cavities in the body. They are not typically associated with granulomas, so this is not the @ Correct Answer. B. Correct: Giant cells: Granulomas often contain multinucleated giant cells, which are formed by the fusion of macrophages in response to persistent irritants or infections. These giant cells play a role in attempting to contain and eliminate the irritant, so this is the @ Correct Answer. C. Incorrect: Lymphocytes are a type of white blood cell that plays a significant role in the immune response. They can be present in granulomas, but they are not the specific cells demarcated by the box. D. Incorrect: Mast cells are immune cells involved in allergic reactions and inflammation. They are not typically a prominent component of granulomas. E. Incorrect: Plasma cells are white blood cells that produce antibodies. They can be found in the immune response to infections but are not typically the primary cells found within granulomas.

20. A patient develops an intra abdominal abscess following appendicitis complicated by perforation. Which of the following bacteriology assays is the best way to distinguish E. coli from Proteus spp. in the specimen obtained from aspiration of this abscess? a. Gram Stain b. Lactose fermentation c. Motility on agar d. Stormy fermentation

Correct Answer: B Rationale: Both E. coli and Proteus spp. are gram-negative bacilli and, thus, would appear similar on Gram stain. One of the main biochemical methods used to identify gram-negative pathogens is lactose fermentation. More Context: A. Incorrect: Both E. coli and Proteus spp. are Gram-negative rods, so a Gram stain wouldn't distinguish between them because they would appear very similar (pink rods) under the microscope. B. Correct: E. coli is a lactose-fermenting organism, meaning it can ferment lactose to produce acid and gas, which can be detected on a lactose-containing medium, turning the medium yellow due to acid production. In contrast, Proteus spp. do not ferment lactose, so the medium remains its original color. Therefore, lactose fermentation provides a differential biochemical characteristic that can distinguish between these two organisms, making this the correct choice. C. Incorrect: Both E. coli and Proteus spp. are motile bacteria; hence, a motility test (typically using semi-solid agar to observe the spreading of the organism) would not differentiate between them since they would both show spreading from the line of inoculation. D. Incorrect: Stormy fermentation is associated with Clostridium perfringens in milk cultures and is not relevant for distinguishing between E. coli and Proteus spp. Therefore, this option is not useful in this context. ● Gram +: Staph, Strep, C Diff ● Motility: Campylobacter jejuni [curved rod], Vibrio cholerae [curved rod], Clostridium, (H pylori), e. coli ● (Stormy fermentation: some anaerobic clostridium, abundance of gas that breaks up clots

8. Which of the following statements is most accurate when responding to a patient's question regarding potential harmful effects of ultraviolet A (UVA) exposure? a. UVA but not UVB transmission is blocked by glass. b. UVA can induce immunosuppression and photocarcinogenesis. c. UVA induces more erythema than exposure to UVB d. UVA is best blocked by use of organic UVB filters.

Correct Answer: B Rationale: Both UVB and UVA contribute to sunlight-induced immunosuppression in humans. Sunscreens with higher UVA protection factors have been shown to improve protection of the elicitation of delayed-type hypersensitivity responses than sunscreens with low levels of UVA protection. It is recommended to use a sunscreen with broad-spectrum activity (providing protection against both UVA and UVB radiation). UVB radiation is more genotoxic than UVA radiation; that said, both UVB and UVA radiation can cause reactive oxygen species (ROS)-mediated damage, which in turn may contribute to UV carcinogenesis. Recall that, although UVA rays play a small role in sunburn, the main concern is that UVA rays penetrate deeper into the skin and cause damage to the cells resulting in premature skin ageing. Other responses were incorrect: UVB induces more erythema than exposure to UVA; UVB is best blocked by use of organic UVB filters; UVB but not UVA transmission is blocked by glass (note that about 75% of UVA passes through ordinary glass). More Context: A. Incorrect: Glass primarily blocks UVB rays and allows a significant amount of UVA to pass through. Therefore, while sitting near a window may protect you from the majority of UVB rays, you are still exposed to UVA rays. B. Correct: UVA rays can penetrate deep into the skin and can cause long-term skin damage and premature aging. Additionally, UVA rays have the ability to suppress the immune system, which can compromise the skin's ability to repair DNA damage, increasing the risk of photocarcinogenesis. C. Incorrect: UVB rays are more responsible for sunburn (erythema) compared to UVA rays. UVB radiation impacts the skin's outer layer and is the primary agent behind sunburns. UVA, conversely, penetrates deeper but does not cause the immediate visible damage seen with UVB exposure. However, it does contribute to skin aging and potentially skin cancer. D. Incorrect: The statement is misleading as it suggests UVB filters are optimal for blocking UVA, which isn't accurate. Sunscreens often contain various filters, each designed to protect against specific types of UV radiation. Broad-spectrum sunscreens are formulated to protect against both UVA and

3. A patient for whom you prescribe ciprofloxacin inquires about how this drug is supposed to "kill the bug" that is causing their acute medical condition. Which of the following is the main therapeutic target of your prescription? a. A potassium channel on the cell membrane b. DNA gyrase c. Peptidoglycan synthesis d. RNA Polymerase

Correct Answer: B Rationale: Ciprofloxacin inhibits topoisomerase/DNA gyrase, which uncoils DNA for DNA synthesis. More Context: A. Incorrect: Ciprofloxacin, a fluoroquinolone antibiotic, doesn't target potassium channels on the bacterial cell membrane. Its mechanism of action is not related to ion channels but is specific to bacterial DNA manipulation by inhibiting enzymes that are crucial for DNA replication and repair. Ex. that does: daptomycin B. Correct: Ciprofloxacin targets DNA gyrase (also known as topoisomerase II), which is a critical enzyme bacteria utilize to manage the supercoiling of their DNA. DNA gyrase introduces negative supercoils (or relaxes positive supercoils) and is essential for DNA replication and repair. By inhibiting this enzyme, ciprofloxacin interferes with the bacteria's ability to replicate and repair its DNA, eventually leading to bacterial death. Ex. that does: fluoroquinolones C. Incorrect: Antibiotics that target peptidoglycan synthesis, such as penicillins and cephalosporins, interfere with bacterial cell wall synthesis. Ciprofloxacin does not operate via this mechanism; its target is intracellular and specific to DNA manipulation, not peptidoglycan synthesis or cell wall construction. Ex. that does: Vancomycin D. Incorrect: While RNA polymerase is a target for some antibiotics (e.g., rifampin), it is not the target for ciprofloxacin. RNA polymerase is crucial for synthesizing RNA from a DNA template, and although it's vital for bacterial survival and replication, ciprofloxacin achieves its antibacterial effect through a different mechanism, specifically by targeting DNA gyrase. Ex. that does: Rifamycins

8. Which of the following factors is most likely to decrease as monoclonal antibody (mAb) structures become more 'humanized' (with increases in 'humanization' from murine mAb → chimeric mAb → human mAb)? A. Complement and antibody-dependent cell-mediated cytotoxicity (ADCC) activation B. Immunogenicity C. Interaction with the neonatal receptor (FcRn) D. Plasma half-life

Correct Answer: B Rationale: Clinical studies have indicated that humanized antibodies are far less immunogenic in humans than are murine antibodies and, in many cases, appear to be virtually nonimmunogenic. As to the difference between humanized and chimeric antibodies, clearly the general trend is that humanized antibodies are less immunogenic. Nonetheless, humanized antibodies are not always completely free from immunogenicity. Depending on target antigens and the sensitivity of assays, weak human anti-humanized antibody responses can be detected in subpopulations of human subjects treated with humanized antibodies. The immunogenicity of monoclonal antibodies in humans is a result of the combination of many factors, including the number of nonhuman amino acids retained, structure and aggregation state of the administered antibody, nature of the antigen, dosing, frequency of administration, and immunocompetence of the patients. Complement and ADCC activation, plasma half-life, and interaction with the neonatal receptor (FcRn) all increase (not decrease) with mAb 'humanization'. More context: A. Incorrect: The "Fc portion" of an antibody is like its backend, and it helps the antibody talk to other immune cells to activate certain defenses (like ADCC and complement). When we make an antibody more "human-like," this communicating part (the Fc portion) usually stays strong or even gets better at its job, not weaker. So, these defense mechanisms do not decrease when antibodies are humanized. B. Correct: When antibodies are made more "human-like" (moving from mouse → partly-human → fully-human), they typically cause fewer unwanted immune reactions in people (they are less immunogenic). Original mouse antibodies can stir up quite a bit of unwanted attention from the human immune system, which might fight against them. Making them more human-like (either partly-human as in chimeric antibodies or fully-human) usually makes them sneakier, and our immune system doesn't notice or attack them as much. C. Incorrect: The FcRn receptor helps antibodies stick around longer in our bodies (it gives them a longer "plasma half-life"). When we humanize antibodies, we try to keep or enhance their interaction with FcRn so

16. A 28-year-old male with a history of HIV presents with fourteen days of fever, night sweats, and swollen lymph nodes under his arms and in his neck. Which of the following pathogens is associated with the rapidly progressive malignancy that is the most likely cause of his symptoms? A. Cytomegalovirus B. Epstein Barr virus C. Herpes simplex virus D. Human papillomavirus

Correct Answer: B Rationale: Epstein Barr virus (EBV) is associated with Burkitt's lymphoma, non-Hodgkin's lymphoma, and nasopharyngeal carcinoma. Human papillomavirus (HPV) is associated with cervical, anal and oropharyngeal cancer. Herpes simplex virus (HSV) and cytomegalovirus (CMV) are not associated with cancer. More context: A. Incorrect: Although CMV can cause fever and is something people with HIV might get, it doesn't cause fast-growing cancers and isn't linked with the quick appearance of swollen lymph nodes (glands), as described here. B. Correct: EBV can be linked with certain fast-growing cancers, such as Burkitt's lymphoma, that might give someone swollen lymph nodes, fever, and night sweats especially in people with HIV. So, this virus fits with the symptoms the person is having and is the right choice. C. Incorrect: HSV can cause various symptoms and can be a concern for people with weaker immune systems, but it isn't linked with causing cancers and so isn't what we're looking for in this case. D. HPV can cause certain cancers, but they don't typically show up as fast-growing lymph nodes and the other symptoms described, so it's not the right answer here. ● HIV → more susceptible to cancer ● All Herpes virus have DNA, are enveloped, and are all latent (this means they can reactive with decreasing T cell immunity)

10. A 64-year-old female with end-stage renal disease requires administration of erythropoietin to maintain a normal hemoglobin and hematocrit. Which of the following is the most likely mechanism of her anemia? a. Decreased iron absorption and marrow utilization of iron by red blood cell precursors b. Decreased production of red blood cell precursors c. Decreased vitamin B12 absorption and purine production in red blood cell precursors d. Increased intravascular hemolysis

Correct Answer: B Rationale: Erythropoietin is a hormone synthesized by the kidney that binds to its receptor on the surface of erythroid progenitors to stimulate hematopoiesis. More context: A. Incorrect: While iron deficiency anemia can occur in individuals with chronic kidney disease due to reduced iron absorption and impaired utilization, the primary cause of anemia in this case is the deficiency of erythropoietin, which is a hormone that stimulates red blood cell production in the bone marrow. Without sufficient erythropoietin, the production of red blood cell precursors is reduced. B. Correct: End-stage renal disease leads to a significant reduction in the production of erythropoietin by the kidneys. Erythropoietin is essential for stimulating the production of red blood cells from precursor cells in the bone marrow. In the absence of adequate erythropoietin, the production of red blood cell precursors decreases, resulting in anemia. C. Incorrect: Vitamin B12 deficiency can lead to megaloblastic anemia, characterized by larger and immature red blood cells, but it is not the primary cause of anemia in this scenario. Erythropoietin deficiency plays a more significant role. D. Incorrect: Intravascular hemolysis refers to the destruction of red blood cells within the bloodstream, which can lead to anemia. However, in end-stage renal disease, the primary issue is the decreased production of red blood cells due to erythropoietin deficiency, rather than their destruction in the bloodstream.

7. Which of the following results in hemolysis due to factors intrinsic to the cell structure? a. Antibodies to red blood cells b. Hereditary spherocytosis c. Mechanical destruction by prosthetic heart valves d. Thrombotic thrombocytopenic purpura

Correct Answer: B Rationale: Hereditary spherocytosis is considered intracorpuscular due to the problem being intrinsic to the red blood cell itself. More context: A. Incorrect: Antibodies to red blood cells represent an extrinsic cause of hemolysis. This means that the factor leading to the destruction of red blood cells (RBCs) originates outside of the RBC itself. Autoimmune hemolytic anemia, for example, involves antibodies that target and lead to the destruction of RBCs but is not related to any intrinsic abnormality within the RBCs themselves. B. Correct: Hereditary spherocytosis does result in hemolysis due to factors intrinsic to the cell structure, making this statement true. It is a genetic disorder that causes a defect in the RBC membrane, leading to spherically shaped RBCs that are more fragile and prone to breaking down (hemolysis). The structural anomaly is intrinsic to the RBC and is not caused by external factors. C. Incorrect: Mechanical destruction by prosthetic heart valves is an example of extrinsic hemolysis, where an external factor (the mechanical stress from the artificial valve) leads to the destruction of RBCs. This does not involve an intrinsic defect within the RBCs themselves but is instead related to an external force that causes hemolysis. D. Incorrect: Thrombotic thrombocytopenic purpura (TTP) involves hemolysis, but it is due to external factors (small blood clots throughout the arteries) rather than an intrinsic abnormality within the RBCs. The clotting that occurs in TTP results in mechanical damage to the RBCs as they pass through the narrowed blood vessels, which is an extrinsic cause of hemolysis.

9. You are explaining to the parents of an infant with a recent diagnosis of sickle cell anemia possible complications that may develop in their child in the future. Which of the following should not be considered a medical emergency? a. Chest syndrome b. Iron overload c. Splenic sequestration syndrome d. Stroke

Correct Answer: B Rationale: Iron overload is a chronic process related to the need for repeat transfusions, not an acute emergency. Sudden acute splenic sequestration can lead to the need for emergency treatment. More Context: A. Incorrect: Chest syndrome is a severe and life-threatening complication of sickle cell anemia. It involves inflammation and blockage of blood vessels in the lungs, which can lead to severe chest pain, shortness of breath, and decreased oxygen levels. Immediate medical intervention, including blood transfusions and oxygen therapy, is required to manage this condition. B. Correct: Iron overload, while a long-term concern in sickle cell disease, is not an acute or immediate emergency. It typically occurs due to the chronic need for blood transfusions in some patients with sickle cell anemia. It can lead to complications over time, such as liver disease or heart problems, but it is not something that requires immediate medical attention. Frequent Blood Transfusions bring in additional iron, which accumulates because the body has limited means to excrete excess iron. SCA can induce a state of ineffective erythropoiesis, which in turn can enhance iron absorption from the gut, contributing further to iron overload. C. Incorrect: Splenic Sequestration Syndrome: Splenic sequestration syndrome is another acute and potentially life-threatening complication of sickle cell anemia. It occurs when a large amount of blood gets trapped in the spleen, causing sudden enlargement and a drop in circulating blood volume. This can lead to shock, severe anemia, and organ failure. It requires urgent medical attention, often including blood transfusions and possible splenectomy (removal of the spleen). D. Incorrect: Stroke: Stroke is a serious complication of sickle cell anemia that can result from the blockage of blood vessels in the brain. It can lead to neurological deficits and even death if not promptly addressed. Immediate medical evaluation and treatment, such as blood transfusions and management of the underlying cause, are essential to minimize the damage caused by a stroke.

5. In this image of peripheral blood, identify the cell highlighted by the arrow. a. Red blood cell b. Lymphocyte c. Macrophage d. Neutrophil e. Plasma cell

Correct Answer: B Rationale: Lymphocytes contain a dark, single nucleus with a thin rim of surrounding cytoplasm.

2. There is a stratum/layer of the epidermis that is mainly formed by polyhedral keratinocytes. Desmosomes maintain the cells in this layer tightly attached to one another, thus the skin can withstand great friction. Which stratum/layer is it? a. Stratum basale or basal layer b. Stratum spinosum or squamous layer c. Stratum granulosum d. Stratum lucidum

Correct Answer: B Rationale: N/A More context: A. Incorrect: The stratum basale is primarily made up of columnar and cuboidal cells. While it does contain keratinocytes (like all layers of the epidermis), these cells are actively dividing and producing new cells to replace those that are shed at the surface. This layer is not mainly known for the tight attachment provided by desmosomes, even though they are present. B. Correct: The stratum spinosum is also known as the spiny layer due to the appearance of the cells when viewed under a microscope, which have a spiny appearance due to the numerous desmosomes that connect the cells. This layer is mainly formed by polyhedral keratinocytes, and the desmosomes play a crucial role in maintaining the cells in this layer tightly attached to one another, providing the skin with the ability to resist tension and friction. C. Incorrect: The stratum granulosum, or granular layer, contains keratinocytes that are becoming more flattened and are beginning to die as they move away from the nutrient supply from the dermis. The cells in this layer have a granular appearance due to the presence of keratohyalin granules. Although they have desmosomes, this layer is not particularly noted for the aspect of resisting friction and tension through those structures. D. Incorrect: The stratum lucidum, or clear layer, is typically found only in thick skin such as that on the palms of the hands and the soles of the feet. This layer is composed of dead, flattened keratinocytes that appear translucent under the microscope. The role and function of the stratum lucidum are not notably associated with resisting friction and tension due to tight cellular adhesion through desmosomes, as the question implies.