November 10, 2019 | Pathology Review for USMLE

Questions 89-102: Genetics and pediatrics

QUESTION 89

A 5-year-old child is being seen by his pediatrician because his parents are concerned regarding his behavior during his first year of school. They are concerned that he has autism. Physical examination reveals large ears and large testicles. Of the following, what type of mutation or chromosomal abnormality underlines this child’s condition?

A. Point mutation
B. Frameshift mutation
C. Trinucleotide repeat
D. A trisomy
E. A monosomy

Answer for Question 89

Answer: C (trinucleotide repeat)

Explanation: the large testicles are characteristic for Fragile X syndrome, in which patients can also have large ears, and which is a common cause of mental retardation, which can present as autism. Fragile X syndrome is due to CGG repeats.

QUESTION 90

A 19-year-old male who plays basketball for his college team is found dead in his dorm room by his roommate. He had an older brother who required a valve replacement and procedure on his aorta two years ago. Autopsy reveals an aortic dissection. A mutated gene for which of the following proteins was the most likely cause of his condition?

A. Elastin
B. Fibrillin
C. Keratin
D. Dystrophin
E. Titan

Answer for Question 90

Answer: B (fibrillin)

Explanation: given that he plays basketball, the assumption can be made that he is tall. Marfan syndrome is autosomal dominant, so two affected brothers is very possible. Features of Marfan syndrome include dilation of the aortic valve ring and a myxomatous mitral valve (or, clinically, mitral valve prolapse, or floppy mitral valve), which would explain the brother’s recent medical procedure. The mutation in Marfan syndrome involves the gene for fibrillin-1. Fibrillin-1 forms a scaffold for tropoelastin, but the mutation is not in the elastin gene itself. Keratin is associated with epithelium and dystrophin and titan are found in the contractile apparatus in striated muscle.

QUESTION 91

A 25-year-old male suddenly becomes short of breath while watching television with friends. Shortly thereafter, he becomes unresponsive. An ambulance is called, but, upon arrival at the emergency room, he is pronounced dead. Autopsy identifies an aortic dissection as the cause of death. The pathologist makes a diagnosis of Marfan syndrome. Which of the following features might also be expected to occur in association with this condition?

A. Short fingers
B. Pes anserinus
C. Colonic adenocarcinoma
D. Hemorrhoids
E. Kyphoscoliosis

Answer for Question 91

Answer: E (kyphoscoliosis)

Explanation: Marfan syndrome is characterized by long fingers (arachnodactyly) not short fingers. Colonic adenocarcinoma and hemorrhoids are not routinely associated with Marfan syndrome. Features of Marfan syndrome include aortic root dilation, myxomatous mitral valve, ectopia lentis, and tall stature. Patients can also have kyphoscoliosis. Pes anserinus is a normal anatomic structure.

QUESTION 92

Molecular analysis of a 10-year-old female, who was identified to have severe scoliosis, reveals a mutation in the gene for lysyl hydroxylase. Neither of her parents have a similar condition. Assuming L is for the normal allele and l is for the mutant allele, of the following, which combination best describes her parent’s genotype?

A. Father: LL; mother ll
B. Father: Ll; mother Ll
C. Father: LL; mother Ll
D. Father: LL; mother LL

Answer for Question 92

Answer: B (Father Ll; mother Ll)

Explanation: the kyphoscoliotic variant of Ehlers-Danlos is due to a mutation in lysyl hydroxylase. This version of Ehlers-Danlos is autosomal recessive, so the patient’s genotype would be ll. To produce a child with an autosomal recessive disorder, when neither of the parent’s manifest the disease, both parents would have to be carriers of the mutation, so Ll.

QUESTION 93

A 24-year-old male is playing basketball with friends when he suddenly develops chest pain. His friends drive him to the emergency room, where he is admitted and diagnosed with a myocardial infarct due to a thrombus occurring in the background of severe coronary artery atherosclerosis. Although he knew about his underlying genetic disorder, he chose to ignore it and did not ever seek treatment. Of the following, what was the mode of inheritance for his underlying condition?

A. Autosomal dominant
B. Autosomal recessive
C. Co-dominant
D. X-linked
E. Mitochondrial

Answer for Question 93

Answer: A (autosomal dominant)

Explanation: familial hypercholesterolemia is due to a mutation in the LDL receptor, which impairs the removal of LDL from the blood. Due to the high concentrations of LDL in the blood, these patients develop atherosclerosis at a young age, and, if untreated, often die of a myocardial infarct in their 20s. Familial hypercholesterolemia is autosomal dominant.

QUESTION 94

A 19-year-old male dies due to sepsis secondary to a pulmonary bacterial infection. At autopsy, sectioning of the lungs reveals plugging of the airways, dilation of airways, and an enlarged right ventricle with a thickened wall. Cultures of the lung grow Pseudomonas aeruginosa. Of the following, which is autopsy examination also likely to reveal?

A. Dilation of aortic root
B. Pancreatic islet metaplasia
C. Pancreatic acinar atrophy
D. Multiple liver hemangiomas
E. Patent ductus arteriosus

Answer for Question 94

Answer: C (pancreatic acinar atrophy)

Explanation: the clinical features are consistent with cystic fibrosis. In cystic fibrosis, mucous in the airways becomes dehydrated, as sodium re-enters cells from the lumen, and water follows. The plugged airways will lead to dilation of the airways (bronchiectasis) and increased strain on the right side of the heart, leading to right ventricular hypertrophy and possible right sided heart failure (cor pulmonale). The changes thus described in the question stem indicate that the process was chronic and not just a one-time occurrence. Pseudomonas aeruginosa is commonly associated with cystic fibrosis, and, on culture, the colonies can be very mucoid in appearance. In addition to recurrent and chronic pulmonary infections, patients with cystic fibrosis also develop pancreatic insufficiency, due to the same changes in the lung (i.e., dehydration mucous leading to plugging of ducts). As the exocrine portion of the pancreas would be impaired from secreting proto-enzymes as normal, the cells would undergo atrophy. Dilation of the aortic root is associated with Marfan syndrome, which is not associated with recurrent pulmonary infections. Liver hemangiomas are associated with von Hippel-Lindau syndrome.

QUESTION 95

A 25-year-old male is seeing his physician because of an inability to have children. His wife of four years was evaluated by her obstetrician and no conditions that would contribute to infertility were identified. After a physical examination and appropriate imaging, the man is determined to have bilateral absence of the vas deferens, which was the cause of his infertility. Of the following, he most likely has a mutation of the gene for which protein?

A. Fibrillin
B. Collagen
C. Glucocerebrosidase
D. CF transmembrane conductance regulator
E. Acid lipase

Answer for Question 95

Answer: D (CF transmembrane conductance regulator)

Explanation: while cystic fibrosis is best associated with recurrent pulmonary infections and pancreatic insufficiency, the number of mutations affecting the CFTR gene is high, and the possible phenotypes are numerous. Individuals with a mutation of the CFTR gene can survive into adulthood and be undiagnosed with the disease, until they present with infertility. In these individuals, bilateral absence of the vas deferens is a common finding.

QUESTION 96

A female neonate immediately after delivery is noted to have a distended abdomen. Forty-eight hours later, she has no passed meconium and has had an episode of bilious emesis. Of the following, what is a complication of her disease process that she will most likely develop during her lifetime?

A. Pancreatic adenocarcinoma
B. Congestive heart failure
C. Aortic dissection
D. Sinusitis
E. Glaucoma

Answer for Question 96

Answer: D (sinusitis)

Explanation: the history presented is consistent with a meconium ileus, which is a complication of cystic fibrosis. The dehydrated secretions can cause plugging of the small intestine. With blockage of the small intestine, a neonate would not pass meconium and they could have bilious emesis. Of the conditions listed, sinusitis is most commonly associated with cystic fibrosis. Due to their production of secretions that are dehydrated, and therefore, thicker and more obstructing, patients with cystic fibrosis can develop pancreatic insufficiency, biliary plugging and eventual cirrhosis, and plugging of the upper respiratory tract, leading to sinusitis.

QUESTION 97

A 25-year-old male is visiting his primary care physician. He has a history of numerous pulmonary infections during his lifetime, several with Pseudomonas aeruginosa as the causative agent. He has also had numerous episodes of diarrhea when not following his prescribed diet and medication regimen. Laboratory testing has revealed elevated concentrations of ALT and AST, and his visit today is to repeat this testing. He is concerned that he may be developing cirrhosis. Of the following, what is the inheritance pattern for his condition?

A. Autosomal dominant
B. Autosomal recessive
C. Co-dominant
D. X-linked recessive
E. X-linked dominant

Answer for Question 97

Answer: B (autosomal recessive)

Explanation: patients with cystic fibrosis often have recurrent and/or chronic pulmonary infections and most develop Pseudomonas aeruginosa. In addition, pancreatic insufficiency is a typical finding in these patients. Due to bile plugging, damage to the liver can occur, and can develop into cirrhosis. Cystic fibrosis is an autosomal recessive disorder.

QUESTION 98

A mother brings her child to an acute care clinic. Her and her husband delivered the child at home and have never sought medical care. The mother reports that she delivered a healthy baby boy, who was able to eat just fine; however, by about 6 months of age, her and her husband felt something was wrong. Six months later, she decided to bring her child to a doctor, as he had not talked and cannot walk. Physical examination reveals a normally developed child with pale hair and pale skin. Auscultation of the chest reveals no murmurs. Palpation of the abdomen reveals no hepatosplenomegaly. Of the following, a deficiency of which enzyme is the cause of this child’s clinical presentation?

A. CF transmembrane conductance regulator
B. Lysosomal glucosidase
C. Glucose-6-phosphatase
D. Glucocerebrosidase
E. Phenylalanine hydroxylase

Answer for Question 98

Answer: E (phenylalanine hydroxylase)

Explanation: the clinical history is consistent with phenylketonuria. If untreated, the elevated concentration of phenylalanine hinders brain development, leading to mental retardation. Patients may never walk or talk. In addition, they can have decreased pigmentation of the hair and skin. The fact that the mother and her husband delivered at home and received no medical care is important, as, neonatal screening will normally detect patients with phenylketonuria, and a phenylalanine free diet can be started and the patients will develop normally. CF transmembrane conductance regulator is associated with cystic fibrosis, which is not associated with neurological conditions. Lysosomal glucosidase is deficient in Pompe’s disease, which affects the heart. Glucose-6-phosphatase is deficient in von Gierke’s disease, which primarily affects the liver and would be associated with hepatomegaly. Glucocerebrosidase is deficient in people with Gaucher disease, which, in most cases, does not involve the central nervous system, and is not associated with the decreased pigmentation.

QUESTION 99

A mother brings her 2-year-old son to an acute care clinic. She explains that she delivered her child at home and has never received medical care; however, her son has not gained weight as she expected, sometimes shakes, and has difficulty walking. Physical examination reveals an enlarged liver. A chest x-ray reveals a normal cardiac silhouette. Examination of the eyes reveals no abnormalities. Of the following, which enzyme is most likely deficient?

A. Glucose-6-phosphatase
B. Muscle phosphorylase
C. Lysosomal glucosidase
D. Galactose-1-phosphate uridyltransferase

Answer for Question 99

Answer: A (glucose-6-phosphatase)

Explanation: a deficiency of glucose-6-phosphatase (von Gierke disease) leads to hypoglycemia, which can induce seizures, and can result in delayed motor development. Patients have hepatomegaly and failure to thrive. Muscle phosphorylase is deficient in McArdle disease, which usually presents in adulthood due to muscle weakness, muscle cramps, and exercise intolerance, and which involves the skeletal muscle only, and therefore would not be associated with hepatomegaly. Lysosomal glucosidase is deficient in Pompe disease, which characteristically affects the heart, causing cardiomegaly. A mild hepatomegaly can also be found in these patients. While deficiency of galactose-1-phosphate uridyltransferase is associated with hepatomegaly and can cause some neurologic changes, cataracts usually occur, and patients often have vomiting or diarrhea after drinking milk.

QUESTION 100

A mother brings her 6-month-old male infant to the pediatrician. She reports that over the past two months, she had had increasing difficulty feeding her baby, and, despite attempts, cannot get her child to stand; she also feels her child is more floppy than he should be. Physical examination reveals an enlarged liver. A chest x-ray reveals an enlarged cardiac silhouette. The child is <10% of age for height and weight. Of the following, what is the most likely enzyme deficiency?

A. Glucose-6-phosphatase
B. Muscle phosphorylase
C. Phenylalanine hydroxylase
D. Lysosomal glucosidase
E. Glucocerebrosidase

Answer for Question 100

Answer: D (lysosomal glucosidase)

Explanation: in patients with deficient lysosomal glucosidase (Pompe disease), they can, when they present early, have liver enlargement, heart enlargement, and can present with feeding difficulties, failure to thrive, and can be hypotonic. Variable terms used for the enzyme are lysosomal glucosidase, α-1,4-glucosidase, and acid maltase). Glucose-6-phosphatase is deficient in von Gierke disease,which affects the liver and leads to hypoglycemia, but does not affect the heart. Phenylalanine hydroxylase has mostly neurological findings, and would not be associated with the heart and liver enlargement. Glucocerebrosidase in most cases does involve the liver, and can, in some cases, involve the central nervous system, but does not involve the heart.

QUESTION 101

A 12-year-old male is brought to the emergency room by his parents because of sudden onset of abdominal pain, which has not resolved over the two hours. Physical examination reveals rebound tenderness and guarding. An exploratory laparotomy reveals peritonitis associated with rupture of the descending colon. Two years ago, this child had emergent surgery to repair rupture of a mesenteric artery. The underlying genetic condition is due to a mutation in the gene for production of which type of collagen?

A. Type I
B. Type II
C. Type III
D. Type IV

Answer for Question 101

Answer: C (Type III).

Explanation: this child has the vascular form of Ehlers-Danlos, which is characterized by rupture of vessels and of the colon. The wall of blood vessels and the colon contains a significant amount of type III collagen, and thus, abnormal type III collagen can predispose to rupture of these organs.

Questions 86-88: Neoplasia

QUESTION 86

A researcher is working with gliomas in an attempt to understand the pathogenesis. One of her projects involves studying a mutated isocitrate dehydrogenase gene. Of the following, by which mechanism does this mutated gene promote neoplasia?

A. Production of 2-hydroxyglutarate
B. Production of a telomerase
C. Promotion of release of E2F
D. Over-production of bcl-2
E. Under-production of bcl-2

Answer for Question 86

Answer: A (production of 2-hydroxyglutarate)

Explanation: mutated isocitrate dehydrogenase genes result in the production of an enzyme that catalyzes the formation of 2-hydroxyglutarate, which inhibits the TET2 family of of enzymes, leading to altered DNA methylation, which causes abnormal expression of genes. Mutated RB gene can result in abnormal release of E2F and promotion of the cell cycle. Over-production of bcl-2 would inhibit apoptosis by stabilizing the mitochondrial membrane, and under-production of bcl-2 could indirectly promote apoptosis and death of the neoplastic cells.

QUESTION 87

A medical student is on a 4th year pathology elective and is sitting at the microscope with their attending physician looking at a biopsy of a cervix. The pathologist points out areas of dysplasia to the medical student. The finding of which of the following features would indicate carcinoma was present within the areas of dysplasia?

A. Markedly increased number of mitotic figures
B. Increase in nuclear:cytoplasm ratio
C. Separate nests of squamous cells resembling the dysplastic cells, but in the dermis
D. Prominent new blood vessel formation
E. Dysplastic cells extending from the basement membrane to the apical surface

Answer for Question 87

Answer: C (Separate nests of squamous cells resembling the dysplastic cells, but in the dermis)

Explanation: A, B, and E are found in areas of dysplasia, with the presence of these features increasing as dysplasia progresses from low grade to high grade. Separate nests of squamous cells resembling the dysplastic cells, but in the dermis would imply invasion, which is a feature of carcinoma. While angiogenesis is a component of neoplasia, the presence of angiogenesis alone would not allow for the diagnosis of neoplasia.

QUESTION 88

A pathologist is examining a prostate biopsy. Focally, within the biopsy is a small cluster of tissue characterized as small glands that are back-to-back, as opposed to the normal prostatic glandular tissue that is characterized by large glands with intervening space. The pathologist determines that the focus of cells is neoplastic. Of the following, what would be the best name for this focus of neoplastic cells?

A. Squamous cell carcinoma
B. Adenocarcinoma
C. Adenosarcoma
D. Leiomyosarcoma
E. Teratoma

Answer for Question 88

Answer: B (adenocarcinoma)

Explanation: as the pathologist is looking at neoplastic glands, the neoplasm is a carcinoma (and not sarcoma, teratoma, lymphoma, or melanoma). As the neoplasm is derived from glands, the appropriate term is adenocarcinoma. Squamous cell carcinoma of the prostate would be rare, but could derive from squamous metaplasia, but the cells of origin are squamous cells.

Questions 74-85: Neoplasia

QUESTION 74

A pathologist is examining a surgically removed mass under the microscope. Of the following, which feature would indicate the mass was malignant?

A. Necrosis
B. A high mitotic rate
C. Nuclear pleomorphism
D. Focal calcification
E. Invasion of surrounding tissue.

Answer for Question 74

Answer: E (invasion of surrounding tissue)

Explanation: although necrosis, a high mitotic rate, and nuclear pleomorphism are commonly found in malignant neoplasms, they can also occasionally be identified in some benign tumors as well, and, as such, are not an absolute marker of malignancy (e.g., nodular fasciitis has a high mitotic rate and nuclear pleomorphism, and can be misdiagnosed as a sarcoma, but, is in fact a benign proliferation). Focal calcification, in areas of necrosis or areas of scarring can also occur in both tumor types. The two characteristic features that distinguish malignant tumors from benign tumors are the ability of malignant tumors to invade surrounding tissue and to metastasize to distant sites; and, of these two, the only one possessed by all malignant tumors is the ability to invade. Basal cell carcinoma of the skin, a malignant tumor, is locally invasive, but rarely metastasizes, and malignant neoplasms of the brain rarely metastasize. Drop metastases associated with a medulloblastoma are not technically metastatic.

QUESTION 75

Prior to an elective laparoscopic cholecystectomy, a 54-year-old male has a chest x-ray as part of his pre-operative work-up. The x-ray reveals a mass in the left lung, which is subsequently surgically excised. The pathologist examining the tissue notes it to be well-circumscribed, firm, and gray-white. Microscopically, he sees disorganizing but otherwise benign-appearing hyaline cartilage. Of the following, what is the best term to describe this mass?

A. Adenoma
B. Chondrosarcoma
C. Hamartoma
D. Choristoma
E. Hyalinoma

Answer for Question 75

Answer: C (hamartoma)

Explanation: a disorganized collection of otherwise normal appearing tissue in an area where that tissue normally occurs is referred to as a hamartoma (cartilage is a normal component of the bronchi). A collection of benign appearing and normally developed cells at an abnormal location (e.g., a nest of adrenal gland cells in the cortex of the kidney), is termed a choristoma. An adenoma is a benign tumor derived from epithelial cells and a chondrosarcoma would be a malignant tumor derived from cartilage. The mass has no features of malignancy.

QUESTION 76

A pathologist is examining a repeat cervical biopsy from a 25-year-old female with a history of multiple sexual partners. She is positive for HPV16. Previous biopsies have revealed mild to moderate dysplasia. Of the following, which microscopic finding would indicate that carcinoma has developed within the dysplastic epithelium?

A. Marked disorganization of cellular maturation from basal to apical layers
B. Numerous mitotic figures throughout the epithelium
C. Hyperchromatic nuclei of various sizes throughout the epithelium
D. Sloughed outer layer of the epithelium
E. Nests of atypical epithelial cells within the superficial dermis

Answer for Question 76

Answer: E (nests of atypical epithelial cells within the superficial dermis)

Explanation: nests of atypical epithelial cells within the superficial dermis would indicate invasion, which is a feature of carcinoma. A-C above, as they are confined to the epithelium are features of dysplasia and would not be indicative, by themself, of carcinoma.

QUESTION 77

A 23-year-old male develops abdominal pain. A CT scan reveals a mass in the liver. A surgical resection is performed. Microscopic examination of the mass by the pathologist reveals a diagnosis of metastatic osteosarcoma. Subsequently, radiologic examination of the right knee reveals a mass. Of the following, which route most likely allowed the neoplasm to spread from the knee to the liver?

A. Spread of tumor cells through the lymphatics
B. Spread of tumor cells through the blood
C. Spread of tumor cells along the surface of nerves
D. Invasion and growth along the lymphatics
E. Invasion and growth along the blood vessels

Answer for Question 77

Answer: B (spread of tumor cells through the blood).

Explanation: While it is not absolute, sarcomas are most known for hematogenous spread. The tumor cells enter the blood vessels and are carried by the blood to distant sites where they implant and grow. Carcinomas are more commonly known for lymphatic spread. While tumors can grow along nerves, distant spread by growing along a nerve would not be a metastasis. Renal cell carcinoma and hepatocellular carcinoma are known for invading into and then growing along blood vessels, but spreading in this manner would not technically be a metastasis, since there is communication with the original tumor site.

QUESTION 78

A neuropathologist is examining a biopsy of a brain tumor at frozen section. Features consistent with a glioblastoma are identified. Molecular analysis of the tumor reveals over-expression of the PDGF gene. This molecular abnormality contributed to which of the following mechanisms by which this tumor developed?

A. Evasion of immune surveillance
B. Sustained angiogenesis
C. Evasion of apoptosis
D. Self-sufficiency for growth signals
E. Insensitivity to growth-inhibitory signals

Answer for Question 78

Answer: D (self-sufficiency in growth signals)

Explanation: PDGF is platelet derived growth factor. In patients with glioblastoma, over-expression of the PDGF gene can occur, resulting in abnormal stimulation of the growth and division of the cell. The cells can grow and divide outside of the normal chain of events and therefore, have developed a self-sufficiency in their growth signals.

QUESTION 79

A young woman is diagnosed with breast cancer after a biopsy of a suspicious mass that had been detected by mammography. The pathologist confirmed the diagnosis of invasive ductal carcinoma and molecular analysis revealed that the tumor was HER2 positive. She received chemotherapy, including anti-HER2 antibodies. Her molecular abnormality contributed to which of the following mechanisms by which this tumor developed?

A. Evasion of immune surveillance
B. Sustained angiogenesis
C. Evasion of apoptosis
D. Self-sufficiency for growth signals
E. Insensitivity to growth-inhibitory signals

Answer for Question 79

Answer: D (self-sufficiency in growth signals)

Explanation: HER2 (also referred to as ERBB2) is a member of the epidermal growth factor receptor family. A mutation in this receptor allowed the patient’s cells to be very sensitive to growth factors, and hence, the development of carcinoma occurred as there was uncontrolled cell growth. When the growth factor receptor is mutated and as a result more responsive to growth factor stimulation, the neoplastic cell has developed self-sufficiency for growth signals.

QUESTION 80

A large medical center that conducts molecular analyses of neoplasms for various small hospitals in the area, specializing in no specific tumor type, conducts a statistical analysis of their last 1000 tumors. Of the following, a mutation of which gene did they see most commonly?

A. ABL
B. MYC
C. ERBB1
D. RAS
E. PTEN

Answer for Question 80

Answer: D (RAS)

Explanation: 30% of all tumors have a mutated RAS, and it is the most commonly identified mutation in human tumors in general. If the medical center had specialized in a specific tumor type, RAS may not have been the most commonly identified oncogene.

QUESTION 81

A 53-year-old male with a 45 pack-year smoking history is diagnosed with pancreatic adenocarcinoma during the work-up of prolonged and unexplained abdominal pain. Molecular analysis of the tumor reveals a mutated RAS gene. Of the following, what was the most likely mechanism by which this mutation contributed to the development of the tumor?

A. Pre-mature hydrolysis of ATP
B. Impaired hydrolysis of ATP
C. Pre-mature hydrolysis of GTP
D. Impaired hydrolysis of GTP

Answer for Question 81

Answer: D (impaired hydrolysis of GTP)

Explanation: mutation of the RAS gene is commonly identified in a pancreatic adenocarcinomas. RAS is a signal transducing protein, a link between the growth factor receptor and the cascade of proteins (PI3K to AKT to mTOR or RAF to MAPK) that lead to activation of transcription factors in the nucleus. When RAS has GTP bound, it is active,and hydrolysis of the GTP inactivates RAS. So, impaired hydrolysis of the GTP would lead to prolonged activation of RAS and abnormal stimulus of nuclear transcription.

QUESTION 82

A pathologist is examining a tumor removed from the left testis of a young boy. Within the tumor, the pathologist identifies squamous epithelium overlying sebaceous glands, hyaline cartilage, neural tissue, and hepatocytes. Of the following, what is the correct name for this tumor?

A. Hamartoma
B. Carcinoma
C. Sarcoma
D. Teratoma
E. Choristoma

Answer for Question 82

Answer: D (teratoma)

Explanation: teratomas, a form of germ cell tumor, have components derived from all three germ cell layers (ectoderm, mesoderm, and endoderm). The skin is derived from ectoderm, the neural tissue is derived from endoderm, and the hyaline cartilage is derived from mesoderm.

QUESTION 83

A pathologist is examining a malignant neoplasm of the lung. Molecular analysis reveals that the tumor has a mutation of the RB gene. Of which of the following mechanisms did the mutation present contribute to the development of the neoplasm?

A. Self-sufficiency in growth signals
B. Insensitivity to growth-inhibitory signals
C. Altered cellular metabolism
D. Evasion of apoptosis
E. Limitless replicative potential

Answer for Question 83

Answer: B (insensitivity to growth inhibitory signals)

Explanation: RB is a tumor suppressor gene. Although it has other functions, when it is hypophosphorylated, the RB protein binds to E2F, which inhibits the transition from G1 to S. When hyperphosphorylation of RB occurs, through actions of Cyclin D/CDK4 and others, E2F is released and transcription occurs. Therefore, RB is growth inhibitory, and mutations to the RB gene will result in an insensitivity to growth inhibitory signals.

QUESTION 84

A researcher is studying the role of apoptosis in breast tissue following a period of lactation after the birth of a child. In their study, they wish to promote apoptosis in samples of lactating breast tissue to study its effects. Promotion of transcription of which of the following genes would best bring about their desired effects?

A. RB
B. Cyclin D
C. MYC
D. TP53
E. GADD45

Answer for Question 84

Answer: D (TP53)

Explanation: the role of TP53 is to identify DNA damage, arrest the cell cycle at G1, trigger repair of the damaged DNA, and if repair is not possible, caused senescence or apoptosis of the cell. Of the genes listed, TP53 is the only one that plays a significant role in the promotion of apoptosis. GADD45 is a DNA repair gene. RB and Cyclin D control the transition from G1 to S.

QUESTION 85

A research oncologist is studying the Warburg effect in neoplastic cells obtained from an individual with small cell carcinoma of the lung. Given that the Warburg effect is present in this cell population, the breakdown of glucose to which of the following substances is expected to be greater than expected?

A. Lactose
B. Water and oxygen
C. Glycine
D. Reactive oxygen species
E. Triglycerides

Answer for Question 85

Answer: A (lactose)

Explanation: in the Warburg effect, neoplastic cells preferentially breakdown glucose to lactose, even in the presence of sufficient oxygen (aerobic glycolysis). While this is an inefficient way to produce ATP, it is a good way to produce other substances required for growth (including proteins, lipids, and nucleic acids). Oxidative phosphorylation efficiently reduces glucose to water and oxygen, producing the maximum amount of ATP, but does not generate substances necessary for cellular growth. Other rapidly growing cells (e.g., during fetal develop) can also exhibit the Warburg effect, so it is not specific to cancer.

Question 65-73: Immune pathology

QUESTION 65

An 11-month-old male is brought to his pediatrician by his parents. They report that he has been pulling at his ear, what they recognize as probably an ear infection, since he has had otitis media four times before. The pediatrician decides to order laboratory tests to check for a primary immunodeficiency. Laboratory testing reveals very low concentrations of Ig in the blood, with IgG, IgM and IgA being affected. Flow cytometry of the blood reveals no B cells. Of the following, what is the most likely diagnosis?

A. Chronic granulomatous disease
B. Selective IgA deficiency
C. Leukocyte adhesion deficiency
D. X-linked severe combined immunodeficiency
E. X-linked agammaglobulinemia

Answer for Question 65

Answer: E (X-linked agammaglobulinemia)

Explanation: X-linked agammaglobulinemia occurs in males and presents after the age of 6 months, once passively transferred maternal antibodies are no longer available. Patients present with recurrent infections with encapsulated bacteria, and can also develop some viral infections. Laboratory testing will reveal very low concentrations of immunoglobulin and absence of B cells, since the defect in X-linked agammaglobulinemia prevents the maturation of B cells from pre-B cells. Chronic granulomatous disease affects the ability of white blood cells to make activated oxygen compounds for the killing of bacteria; in many cases it is also X-linked and would be present in males, but the diagnosis is usually made in early childhood. Selective IgA deficiency involves only a deficiency of IgA and presents later in life. Leukocyte adhesion deficiency involves a protein that enables neutrophils to adhere to the endothelium. Symptoms begin in infancy, and at birth, delayed detachment of the umbilical cord can occur, but the disease would not cause low concentrations of immunoglobulin, or absence of B cells. In X-linked severe combined immunodeficiency, most patients present at less than 6 months, with failure to thrive due to disseminated infections such as candidiasis and Pneumocystis. Laboratory testing would reveal decreased T cells. The number of B cells can be normal or increased.

QUESTION 66

A 14-month old male is brought to the pediatrician by his parents because he has been coughing up a thick green mucous. A chest x-ray reveals consolidation of the lower lobe of the right lung. Three months ago, he had an episode of otitis media and seven months ago, he had been diagnosed with Haemophilus influenzae pneumonia. Flow cytometry of the blood reveals an absence of B cells. Of the following, which is he most likely to develop in the future?

A. Disseminated Candidiasis
B. Infectious mononucleosis due to Epstein-Barr virus
C. Giardia lamblia induced diarrhea
D. Aspergillus pneumonia
E. Mycobacterium tuberculosis pneumonia

Answer for Question 66

Answer: C (Giardia lamblia induced diarrhea)

Explanation: given that the patient is male and greater than 6 months of age, and presenting with recurrent bacterial infections of the lung and ear, including with an encapsulated organism (Haemophilus influenzae), and with the laboratory testing revealing an absence of B cells, the clinical presentation would be consistent with a diagnosis of X-linked agammaglobulinemia. Patients with X-linked agammaglobulinemia are most susceptible to infections with encapsulated bacterial organisms (Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Neisseria meningitidis), GI parasites (Giardia and Cryptosporidium) due to lack of IgA, and enteroviruses (which enter the body through the gastrointestinal tract). Infection with Epstein-Barr virus requires the presence of B cells.

QUESTION 67

A 23-year-old female is in a motor vehicle accident and fractures her femur. At the hospital, she requires a blood transfusion in the emergency room, prior to surgery. Her only past medical history is recurrent sinusitis and a past skiing accident that caused a significant laceration, with blood loss requiring transfusion. After receiving the transfusion for the femoral fracture, she develops shortness of breath and requires intubation to protect her airway. Of the following, what is her most likely underlying diagnosis?

A. X-linked agammaglobulinemia
B. Severe combined immunodeficiency
C. Ataxia-telangiectasia
D. Selective IgA deficiency
E. Wiskott-Aldrich syndrome

Answer for Question 67

Answer: D (Selective IgA deficiency)

Explanation: given the past history of sinusitis and the age of the patient, selective IgA deficiency is the best choice. In patients with selective IgA deficiency, transfusion with blood can lead to the development of anti-IgA antibodies, which, when transfused again, can lead to an anaphylactic reaction. X-linked agammaglobulinemia as well as Wiskott-Aldrich are X-linked and would not normally present in a female, and Wiskott-Aldrich normally presents in infants. Severe combined immunodeficiency would present in infancy and, while ataxia-telangiectasia is autosomal recessive and can present in females and at a later age, her past medical history does not include mention of ataxia or telangiectasias.

QUESTION 68

Over the past seven hunting seasons, a 35-year-old male has twice developed Giardia lamblia. Although he admits to routinely drinking water from streams when hunting, his physician decides to order some laboratory tests to evaluate his condition. His past medical history is significant only for the recent development of rheumatoid arthritis. He is up-to-date on his vaccinations, and post-hepatitis vaccination testing revealed normal development of protective antibodies. Laboratory testing reveals a significantly decreased concentration of IgA. Of the following, what else would laboratory testing reveal?

A. Normal IgG; Normal IgM
B. Normal IgG; Decreased IgM
C. Normal IgGl Increased IgM
D. Decreased IgG; normal IgM
E. Decreased IgGl decreased IgM

Answer for Question 68

Answer: A (normal IgG; normal IgM)

Explanation: given his age and the fact that he developed two Giardia lamblia infections, which is an intestinal disease process, a selective IgA deficiency is possible, which is confirmed by the laboratory testing. Patients with selective IgA deficiency also are at risk for the development of an autoimmune disease. Given his age and the presence of the autoimmune disorder, a common variable immunodeficiency would also be possible, and with this condition, the IgG concentration could be decreased; however, as the patient mounted an appropriate response to his vaccinations, common variable immunodeficiency is much less likely as these patients usually have a poor response to vaccination. In selective IgA deficiency, the IgG and IgM concentrations will usually be normal.

QUESTION 69

A 17-year-old female has had frequent episodes of otitis media during her lifetime as well as four serious cases of pneumonia, and one episode of Giardia lamblia induced diarrhea. During a follow-up examination after her diarrhea resolved, laboratory testing reveals decreased concentrations of IgG and IgA; however, flow cytometry reveals an increased number of CD19+ cells. Of the following, a biopsy of the gastrointestinal tract is most likely to reveal?

A. Amoeba
B. Hyperplastic follicles
C. Hypoplastic follicles
D. Amyloid deposition
E. Acute colitis

Answer for Question 69

Answer: B (hyperplastic follicles)

Explanation: given the age of the patient and recurrent infections of the sinopulmonary and GI tract, combined with the laboratory testing, the most likely diagnosis is a common variable immunodeficiency, which can present in females and normally presents later in life. In common variable immunodeficiency, the number of B cells is increased; however, no differentiation to plasma cells occurs. B cells can proliferate in response to an infection, so areas that contain B cells (e.g., lymphoid follicles) can be hyperplastic. These patients do not overproduce a protein, so amyloidosis would not be expected.

QUESTION 70

A 6-year-old male is being seen by his pediatrician for a routine follow-up visit. He has had difficulty learning to walk, has had two episodes of pneumonia requiring hospitalization, and recently his parents have noticed small red nodules on his right eyelid and left ear. Laboratory testing reveals a decreased concentration of IgA. Of the following, what is the inheritance pattern for his condition?

A. Autosomal dominant
B. Autosomal recessive
C. Co-dominant
D. X-linked
E. Mitochondrial

Answer for Question 70

Answer: B (autosomal recessive)

Explanation: the child has ataxia-telangiectasia. This disease process often presents after the age of 5 years. His difficulty walking is a manifestation of the ataxia and the small nodules on his eyelid and ear are telangiectasias. Patients often have decreased IgA. Ataxia-telangiectasia is inherited in an autosomal recessive pattern.

QUESTION 71

A 13-year-old female is having surgery to remove CNS lymphoma that was diagnosed after she had a seizure. During her life, she has had difficulty walking and her speech has of lately been slurred, which was not attributed to the cerebral neoplasm. Physical examination prior to the surgery reveals numerous small red nodules on her body, including her eyelids, antecubital fossa, and sides of the neck. Of the following, laboratory testing would reveal an elevated concentration of which substance, which is used for diagnosis of her underlying condition?

A. IgA
B. IgG2
C. Alpha-fetoprotein
D. Alanine aminotransferase
E. Creatinine kinase

Answer for Question 71

Answer: C (Alpha-fetoprotein)

Explanation: the red nodules on her eyelids and skin are telangiectasias, and her difficulty walking and slurred speech are manifestations of ataxia. Patients with ataxia-telangiectasia are at risk for development of neoplasms, especially lymphoid neoplasms. Individuals with ataxia-telangiectasia can have decreased concentrations of IgA and IgG2. An increased concentration of alpha-fetoprotein is used in the diagnosis of ataxia-telangiectasia.

QUESTION 72

A 2-year-old male is seen by his pediatrician for follow-up of his chronic disease process. He receives daily doses of calcium and vitamin D and, shortly after birth, underwent heart surgery to repair his Tetralogy of Fallot. Of the following, what is the location of the deletion causing his condition?

A. 22q11
B. 22q12
C. 21q11
D. 21q12
E. 11q22
F. 11q12

Answer for Question 72

Answer: A (22q11)

Explanation: hypocalcemia and heart defects are characteristic of Tetralogy of Fallot. The disease can be either complete or partial, depending upon the involvement of the immune system. In partial DiGeorge syndrome, patient’s have preserved T cell function, and their hypoparathyroidism can be treated with calcium and vitamin D supplementation. Congenital heart defects can include Tetralogy of Fallot, truncus arteriosus, and atrial or ventricular septal defects. The deletion occurs at 22q11.

QUESTION 73

At 36 hours after birth, a term female infant is noted by her mother to have muscular spasms. A physician orders stat testing for calcium. The calcium concentration is low. Following the resolution of the muscular spasms, an echocardiogram is performed, which reveals a ventricular septal defect, right ventricular hypertrophy, and an incomplete obstruction of the right ventricular outflow tract Flow cytometric analysis of the blood reveals normal numbers of B lymphocytes, but absent T lymphocytes. A lateral chest x-ray would reveal which of the following?

A. Scoliois
B. Thymic aplasia
C. Thymic hyperplasia
D. Consolidation of one lobe of a lung
E. Absence of the aorta

Answer for Question 73

Answer: B (thymic aplasia)

Explanation: hypocalcemic tetany (i.e., the muscle spasms) occurring shortly after birth, in association with hypocalcemia and in the background of Tetralogy of Fallot is consistent with DiGeorge syndrome, with the hypocalcemia being due to parathyroid gland hypoplasia. Patients also have thymic abnormalities, manifested as thymic aplasia and resultant defects in T lymphocyte function, predisposing to infections with viruses, fungi, parasites, and intracellular bacteria. The B cell function is un-disturbed, and thus, patients will have normal numbers of B lymphocytes. Scoliosis is not a characteristic feature of this disease process, and they are most at risk for fungal, parasite, and viral infections. While the aorta can be abnormal (i.e., an interrupted aortic arch), absence of the aorta would be incompatible with life.

Questions 58-64: Hemodynamics

QUESTION 58

A medical student is watching a presentation on Budd-Chiari syndrome, which is due to thrombosis of major hepatic veins. During the presentation, a pathologist shows a slide with a microscopic image of the liver. Changes consistent with which of the following processes would be present around the central veins?

A. Acute congestion
B. Chronic congestion
C. Acute hyperemia
D. Chronic hyperemia

Answer for Question 58

Answer: A (acute congestion)

Explanation: thrombosis of major hepatic veins should present acutely as there is greatly reduced ability for blood to exit the liver, effectively blocking its flow. With obstruction of venous outflow from the liver, blood will back up into the central veins, which is a passive process, and hence congestion. Given that it happened suddenly, it is an acute process. So, the appropriate process would be acute congestion. Hyperemia is an active process, such as occurs with vasodilation during acute inflammation. Chronic hyperemia would essentially never occur, because it would require an active process to constantly stimulate dilation of the vessels.

QUESTION 59

During their rotation in the emergency room, on one day, a medical student saw a patient with prominent swelling of their left upper extremity and a light red-pink discoloration and a patient with prominent swelling of both lower extremities and a dark red-blue discoloration. Of the following, the concentration of which compound accounts for the color difference?

A. Carbon dioxide
B. Oxygen
C. Nitrogen
D. Carbon monoxide
E. Methemoglobin

Answer for Question 59

Answer: B (Oxygen)

Explanation: in hyperemia, patients have an active process that causes dilation of blood vessels (e.g., acute inflammation). Because of the dilation of the blood vessels, the vessels become filled with oxygenated blood, which imparts a lighter red-pink coloration to the tissue. In congestion, patients have a passive process that causes dilation of blood vessels (e.g., failure of the heart leading to back-up in the venous system). The blood that accumulates is deoxygenated blood, which will impart a dark red blue discoloration to the tissue.

QUESTION 60

A 64-year-old male with congestive heart failure due to end-stage systemic hypertension presents to his primary care physician. Physical examination reveals rales and pitting edema of the lower extremities. Of the following, which mechanism was most responsible for his physical findings?

A. Increased hydrostatic pressure
B. Decreased hydrostatic pressure
C. Increased plasma osmotic pressure
D. Decreased plasma osmotic pressure

Answer for Question 60

Answer: A (increased hydrostatic pressure)

Explanation: with congestive heart failure, failure of the ventricles to be able to effectively pump blood leads to congestion within the venous systems (i.e., systemic venous system with failure of the right side of the heart and pulmonary venous system with failure of the left side of the heart). An increased amount of blood in the veins will distend the vessel, thereby increasing the hydrostatic pressure, which will promote the leakage of fluid from the vessel into the surrounding tissue and hence, edema.

QUESTION 61

A 34-year-old pregnant female is brought to the emergency room by her husband because she suddenly became short of breath and developed chest pain. A spiral CT scan reveals a peripherally located thromboembolus in the lower lobe of her left lung. Physical examination revealed that the left thigh and calf had a greater diameter than the right thigh and calf. Of the following, which mechanism was responsible for the physical examination findings?

A. Increased hydrostatic pressure
B. Decreased hydrostatic pressure
C. Increased plasma osmotic pressure
D. Decreased plasma osmotic pressure

Answer for Question 61

Answer: A (increased hydrostatic pressure)

Explanation: a pulmonary thromboembolus is a complication of a venous thrombosis, most commonly of the deep veins in the lower extremities. Because of the thrombosis of the vein, blood will pool in the venous system distal to the thrombosis as it cannot go around the site of blockage. An increased amount of blood in the veins will distend the vessel, thereby increasing the hydrostatic pressure, which will promote the leakage of fluid from the vessel into the surrounding tissue and hence, edema of the lower extremities, which would appear on physical examination as an increased girth of the affected extremity.

QUESTION 62

A 41-year-old alcoholic male presents to an acute care clinic complaining that his stomach has been getting larger lately. Physical examination reveals a fluid wave, consistent with ascites. Of the following, which two mechanisms are most responsible for his physical examination findings?

A. Increased hydrostatic pressure; increased plasma osmotic pressure
B. Increased hydrostatic pressure; decreased plasma osmotic pressure
C. Decreased hydrostatic pressure; increased plasma osmotic pressure
D. Decreased hydrostatic pressure; decreased plasma osmotic pressure

Answer for Question 62

Answer: B (increased hydrostatic pressure; decreased plasma osmotic pressure)

Explanation: a certain proportion of alcoholics develop cirrhosis of the liver and patients with cirrhosis of the liver can develop ascites (accumulation of watery fluid in the abdominal cavity). The scarring of the liver associated with cirrhosis causes some degree of obstruction of venous blood flow through the liver, which contributes to increased hydrostatic pressure, leading to edema. In addition, the liver produces albumin, which is the main protein in the blood and hence, the largest contributor to the plasma osmotic pressure. Damage to the liver leads to a decreased production of albumin and thus, decreased plasma osmotic pressure, leading to edema.

QUESTION 63

A 42-year-old female is presenting to her general surgeon for a visit after having undergone a partial mastectomy and lymph node dissection of the right breast for the treatment of invasive ductal carcinoma. The surgeon notes during physical examination and as reported by the patient that her right arm and forearm are swollen. Of the following, which is the most likely mechanism responsible for this physical examination finding?

A. Increased hydrostatic pressure
B. Decreased hydrostatic pressure
C. Increased plasma osmotic pressure
D. Decreased plasma osmotic pressure
E. Localized sodium retention
F. Lymphatic obstruction

Answer for Question 63

Answer: F (lymphatic obstruction)

Explanation: with a lymph node dissection, the flow of lymph can be disrupted; as lymph serves to return fluid to the heart that does not make its way back into the venous vasculature, obstruction of lymphatic flow will cause edema, which could produce enlargement of the right upper extremity. While it could be argued that increased hydrostatic pressure due to loss of veins and thereby resultant obstruction of venous flow, which would lead to edema, could result, during the surgery, preservation of the vasculature as best as possible could occur, whereas, a lymph node dissection, by its nature, would be damaging to the lymphatic system. Current techniques very greatly minimize the risk of such occurrences (i.e., lymphatic obstruction post surgery); however, understanding the complication and its mechanism is still useful.

QUESTION 64

During a wrestling competition, an amateur wrestler, while dead-lifting 300 lbs, develops tiny pinpoint red dots on his eyelids. Of the following, which would be the best descriptive term to use for these lesions?

A. Hemorrhage
B. Purpura
C. Ecchymoses
D. Bruising
E. Petechiae

Answer for Question 64

Answer: E (petechiae)

Explanation: various terms are used to describe hemorrhages in the skin and mucous membranes. These terms are based upon the size. Pinpoint hemorrhages (1-2 mm) are referred to as petechiae. Purpura are larger (3-5 mm) and can be raised (i.e., palpable). Ecchymoses are even large (1-2 cm or more). A hemorrhage is a non-specific term that applies to all three. Bruising is another term for ecchymosis.

Questions 46-57: Inflammation and repair

QUESTION 46

A 1-year-old child has had recurrent skin infections. Laboratory testing has revealed elevated white blood cell counts. Molecular testing revealed a defect in the β subunit of CD18 on leukocytes. Of the following, which phase of the neutrophil response during inflammation was most affected?

A. Margination
B. Rolling
C. Adhesion
D. Migration through the endothelium
E. Chemotaxis

Answer for Question 46

Answer: C (adhesion).

Explanation: the child has leukocyte adhesion deficiency, the most common form of which is due to an autosomal recessive mutation involving the β sub-unit of CD18. CD18 is a component of integrins (both LFA-1 and MAC-1). LFA-1 is present on neutrophils and plays a role in adhesion. ICAM-1 on the activated endothelium binds to LFA-1 on the neutrophil causing the neutrophil to adhere to the endothelium. Margination occurs because of vasodilation. Rolling is due to the interaction of selectins and sialyl-Lewis X. Migration through the endothelium involves CD31 (PECAM-1) and agents of chemotaxis (i.e., movement of the leukocyte to the site of injury) are C5a, LTB4, and bacterial peptides.

QUESTION 47

A 13-year-old male was diagnosed just shortly after birth with tetralogy of Fallot following auscultation of a murmur. At 4 days of age, laboratory investigation of jerking motions of his lower extremities revealed a calcium concentration of 4.6 mg/dL. Of the following, fluorescence in-situ hybridization (FISH) would most likely reveal a deletion of?

A. 21q11.1
B. 21q11.2
C. 22q11.1
D. 22q11.2
E. Y chromosome

Answer for Question 47

Answer: D (22q11.2)

Explanation: cardiac defects and hypocalcemia along with T cell immunodeficiency and facial abnormalities are consistent with 22q11.2 deletion syndrome. Previous terminology included DiGeorge syndrome, when the main manifestations were the hypocalcemia and the T cell immunodeficiency, and velocardiofacial syndrome, when the main manifestations were facial dysmorphology and congenital cardiac disease. Both were due to deletions at 22q11.2, with the exact location of the deletion determining the subsequent phenotype of the patient.

QUESTION 48

A 13-year-old girl is roller skating with her friends when a dog runs out in front of her, causing her to crash, during which time, she strikes her left elbow hard on the sidewalk. She returns home and tells her mother what she did. Her mother notices that her left elbow has begun to swell. Of the following, which mediator was most responsible for this change?

A. Histamine
B. CD11a/CD18
C. Leukotriene B4
D. Toll-like receptor
E. C3b

Answer for Question 48

Answer: A (histamine)

Explanation: because of the fall and striking her left elbow, this girl has initiated an acute inflammatory response. The first manifestation is usually swelling, which is due to vasodilation of the vasculature and increased membrane permeability through separation of endothelial cells, which allows for fluid to leave the blood vessel and enter the surrounding soft tissue, hence, the swelling. Histamine is an important mediator in causing this change. CD11a/C18 plays a role in attachment of neutrophils to the endothelium; leukotriene B4 is a chemoattractant; Toll-like receptor plays a role in the body’s ability to identify microbes, and C3b is an opsonin, which allows phagocytes to ingest microbes and other foreign substances.

QUESTION 49

A 13-year-old girl has been having a cough and fever for the last four days, and over the last day developed some difficulty breathing. Her parents did not take her to the emergency room, because they knew a cold was going around. In the morning, they found her unresponsive in her bed. An ambulance was called, but she was pronounced dead. An autopsy was performed, and in the left pleural cavity was a thick white-yellow cloudy fluid substance. Microscopic examination of the lungs confirmed a lobar pneumonia. Of the following, which term best described the substance in the left pleural cavity?

A. A serous exudate
B. A purulent exudate
C. A serous transudate
D. A fibrinous transudate
E. A purulent transudate

Answer for Question 49

Answer: B (a purulent exudate)

Explanation: one complication of pneumonia is pleuritis. In this case, the left pleural cavity was filled with pus (i.e., an empyema). Being cloudy, the fluid is filled with cells. A serous fluid is watery and should be clear. An exudate has an increased amount of protein and most often cells; whereas a transudate is mostly just fluid, with a low protein content and essentially no cells. So, fibrinous and transudate should be mutually exclusive as would purulent and transudate, as a purulent fluid is one filled with neutrophils. A serous exudate is also mutually exclusive.

QUESTION 50

A researcher wants to develop a drug that decreases the acute inflammatory response. The hypothesis is that if neutrophils can be prevented from contacting the endothelium that the acute inflammatory response can be blunted, which may help some patients. Of the following, which mediator would be the best target for the drug?

A. CD31
B. LFA-1
C. P-selectin
D. ICAM-1
E. Toll-like receptor

Answer for Question 50

Answer: C (P-selectin)

Explanation: the researcher hopes to block the rolling stage of acute inflammation. In the rolling stage, Sialyl-Lewis-X molecules on the neutrophils bind to E- or P-selectin molecules on the surface of the endothelium causing loose binding of the white blood cells to the capillary wall. LFA-1 (on neutrophils) binds to ICAM-1 on endothelial cells, leading to adhesion. CD31 (PECAM) plays a role in transmigration and Toll-like receptor plays a role in recognition of microbes.

QUESTION 51

Two individuals rescued from a house fire are brought to the emergency room. One sustained a large bruise on the left forearm when a beam collapsed and struck them and the other sustained 9% body surface area burns on their trunk. The bruise swells for a short period of time and then the swelling dissipates; however, the burn continues to weep fluid, requiring frequent dressing changes over the course of two weeks. What did the burn victim sustain that the contused individual did not?

A. Rapid release of histamine
B. Delayed release of serotonin
C. Activation of CD31
D. Bacterial superinfection
E. Endothelial necrosis

Answer for Question 51

Answer: E (endothelial necrosis)

Explanation: both individuals have evidence of increased vascular permeability, with fluid leaking from the vessel into the surrounding tissue. Increased vascular permeability can occur by two mechanisms: endothelial retraction or endothelial damage. Endothelial retraction as mediated by histamine rapidly leads to increased vascular permeability but the effect is short lived, such as occurred in the individual with the bruise. Endothelial damage occurs rapidly, but is long lived, requiring replacement of the damaged endothelium during the repair process. This can occur in burns, or due to the effects of a bacterial, or other microbial infection. While a bacterial superinfection can occur in a burn patient, it is not required to have continued loss of fluid.

QUESTION 52

A pathologist is examining sections from the heart of an individual who sustained an acute myocardial infarct and subsequently died. In the section, the pathologist notes coagulative necrosis and a brisk neutrophilic response, with large aggregates of neutrophils scattered throughout the tissue. No macrophages are identified and all neutrophils appear intact. Of the following, what was the time frame between the occurrence of the infarct and the individual’s death?

A. 5 seconds
B. 15 minutes
C. 3 hours
D. 1 day
E. 1 week

Answer for Question 52

Answer: D (1 day)

Explanation: although an acute inflammatory infiltrate begins immediately after the time of injury, the gross and microscopic changes take some time to develop. As vasodilation and fluid exudation is rapid, red discoloration and swelling can be seen within minutes; however, development of the neutrophilic response described would take a little time. Following the acute inflammatory response, macrophages would move in to clean up the mess. After 5 seconds and 15 minutes, no neutrophils would be expected. While neutrophils may be present at 3 hours, a significant infiltrate on microscopic examination would not be identified; at 1 week, the neutrophilic response should have ended (usually by a few days), the macrophage response should be complete or nearly completed (with macrophages beginning to enter the picture around 2-3 days).

QUESTION 53

A pathologist is examining a section of gallbladder that was resected from a patient having abdominal pain. Of the following, which would indicate the patient had chronic cholecystitis instead of acute cholecystitis?

A. Neutrophilic infiltrate
B. Edema of the wall of the gallbladder
C. Dilated blood vessels
D. New blood vessel formation

Answer for Question 53

Answer: D (new blood vessel formation).

Explanation: the first three answers (neutrophilic infiltration, edema of the tissue, and dilated blood vessels) are found in acute inflammation. New blood vessel formation along with fibrosis, infiltrates of mononuclear cells (e.g., macrophages and lymphocytes), and tissue destruction are features of chronic inflammation.

QUESTION 54

A 52-year-old male is found dead in his house during a welfare check by police. At autopsy, he is found to have an organizing thrombus in the left anterior descending coronary artery and a corresponding infarct of the anterior wall of the left ventricle. Microscopic examination of the infarct reveals some neutrophils, but also a prominent number of macrophages, which have engulfed necrotic debris and degenerating neutrophils. Which of the following mediators activated the macrophages?

A. IL-13
B. IFN-γ
C. Eotaxin
D. TGF-β
E. C5a

Answer for Question 54

Answer: B (IFN-γ)

Explanation: the macrophages present at the infarct would be classically activated macrophages, responsible for removing the dead cells. IFN-γ is a major mediator for activating macrophages through this pathway. IL-13 activates macrophages through the alternative pathway, and macrophages activated via this pathway (M2 macrophages) promote wound repair, including fibrosis and angiogenesis. Eotaxin is chemoattractive for eosinophils and C5a stimulates release of histamine, and is also chemoattractive for neutrophils, monocytes, and basophils. TGF-β is secreted by activated macrophages and promotes fibrosis during wound repair.

QUESTION 55

A pathologist is examining a lung biopsy in a patient suspected of having tuberculosis. Numerous granulomas are identified throughout the biopsy. An acid-fast stain reveals occasional acid-fast bacilli, consistent with tuberculosis. Of the following, what did every granuloma have?

A. Giant cells
B. A fibrous rim
C. A rim of lymphocytes
D. Central necrosis
E. Epithelioid histiocytes

Answer for Question 55

Answer: E (epithelioid histiocytes)

Explanation: a granuloma is composed of epithelioid histiocytes, which are large eosinophilic macrophages [histiocyte is another term for macrophage]. While granulomas can individually possess any of the other features listed (giant cells, a fibrous rim, a rim of lymphocytes, or caseous necrosis), the only feature listed that all granulomas possess is the epithelioid histiocytes.

QUESTION 56

A 19-year-old female presents to an acute care clinic with complaints of fever, chills, and a productive cough that has been lasting for 3 days. An x-ray reveals consolidation of the lower lobe of her left lung. A diagnosis of lobar pneumonia is made. Laboratory testing reveals a white blood cell count of 18,000 cells/mL. Which of the following mediators was most responsible for her clinical presentation?

A. IL-1
B. IL-2
C. IL-3
D. IL-4
E. IL-5

Answer for Question 56

Answer: A (IL-1)

Explanation: IL-1 (also TNF and IL-6) are responsible for producing the acute phase response in patients with acute infections. The acute phase responses include fever, elevated acute phase proteins (e.g., C-reactive protein and fibrinogen), leukocytosis, and also increased heart rate and blood pressure.

QUESTION 57

A 22-year-old male slides into the plate during a league softball game and scrapes his left knee. Penetration through which of the following layers indicates that he is most likely to develop a scar?

A. Stratum corneum
B. Stratum granulosum
C. Stratum spinosum
D. Stratum basale
E. Basement membrane

Answer for Question 57

Answer: E (basement membrane).

Explanation: With the squamous epithelium of the skin having such good regenerative capabilities, injury to the epidermis will result in complete resolution, however, once the injury perforates the basement membrane, complete resolution is no longer possible and a scar will result.