Month: November 2019

Answer: C (stable angina)

Explanation: the man has multiple risk factors for atherosclerosis (age, sex, hypertension, diabetes mellitus, and smoking history). Given the chronicity of the symptoms (i.e., occurring over a 6 month time period), aortic dissection, unstable angina, and acute myocardial infarct are all unlikely, as these are acute events. The symptoms are characteristic for stable angina, which is caused by coronary artery atherosclerosis. When the plaque reaches a critical degree of stenosis (70-75%), during exercise an adequate amount of blood to oxygenate the myocardium can no longer reach the heart, and chest pain occurs. While metastatic lung carcinoma, given the smoking history, is possible, compared to stable angina, would be a rare cause of such a clinical presentation.

Answer: C (an atheroma producing 75% stenosis)

Explanation: the symptoms, a pressure-like chest pain occurring during exertion and resolving at rest, in an older male with hypertension, diabetes mellitus, and a history of smoking, are consistent with stable angina. Stable angina is caused by a significantly stenotic atherosclerotic plaque. A 70-75% stenosis is considered significant; with less stenosis than this most often being asymptomatic. While a non-occlusive thromboembolus, such as from a mural thrombus after a myocardial infarct, or associated with a dilated cardiomyopathy could cause angina, it should present acutely, and be a sudden change. Coronary artery dissections are rare, and, while a partial dissection could cause stable angina (i.e., if the dissection occurred, then stopped, then resolved), it would be a very rare compared to atherosclerosis as a cause.

Answer: D (endothelial dysfunction)

Explanation: give a cardiac origin, the symptoms, a pressure-like chest pain occurring during exertion and resolving at rest, in an older male with hypertension, diabetes mellitus, and a history of smoking, are consistent with stable angina. The most common cause of stable angina is coronary artery atherosclerosis. The initiating step in coronary artery atherosclerosis is endothelial dysfunction, which can be induced by a variety of factors (i.e., cardiac risk factors). Once the endothelium becomes dysfunctional, it will promote thrombosis and allow attachment of white blood cells when it should not. White blood cells in the intima release reactive oxygen species and lead to oxidation of LDL, which accumulates in macrophages.

Answer: C (erythrocyte sedimentation rate)

Explanation: given a cardiac origin, the symptoms, a pressure-like chest pain occurring during exertion and resolving at rest, in an older male with hypertension and a history of smoking, are consistent with stable angina. The most common cause of stable angina is coronary artery atherosclerosis. In stable angina, there is no irreversible injury to cardiac myocytes, so troponin I and CK-MM (and CK-MB) should be within normal range. ASO titer (anti-streptolysin-O) is indicative of a previous Group A streptococcal infection, which is possible, but is not directly related to his disease process. Erythrocyte sedimentation rate is elevated in a variety of diseases, including coronary artery atherosclerosis. As a component of atherosclerosis is inflammation, and as ESR can be a marker for inflammation, ESR can be elevated; however, it is non-specific as a screening method for coronary artery disease.

Answer: D (Coronary artery angiogram)

Explanation: the patient has several risk factors for coronary artery atherosclerosis, including age, sex, hypertension, diabetes mellitus, and hypercholesterolemia. The symptoms, given they occur with exertion and resolve within a few minutes, and can be associated with nausea, dyspnea, and radiation into the arm, are consistent with angina. A coronary artery angiogram would confirm the diagnosis.

Answer: D (Diabetes mellitus)

Explanation: the symptoms are consistent with angina. The main cause of angina is coronary artery atherosclerosis. Major risk factors for coronary artery atherosclerosis include age >55 years in males, diabetes mellitus, hypertension, tobacco use, and hypercholesterolemia. Chronic alcoholism, metastatic tumor, high concentrations of HDL and recurrent sinus infections are not associated with coronary artery atherosclerosis. Low concentrations of HDL are a risk factor for atherosclerosis.

The image is liver. There is ballooning degeneration of hepatocytes (i.e., enlarged swollen hepatocytes). At the yellow arrow is bile (i.e., bile stasis) and at the black arrow is Mallory hyaline.

Steatosis of the liver–nearly every hepatocyte contains a large vacuole (macrovesicular steatosis). A common cause of steatosis of the liver is alcohol use. Other causes include obesity and diabetes mellitus. In the left upper quadrant is a portal tract.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Answer: B (physiologic hypertrophy)

Explanation: as a member of the track and field team, hypertrophy of the muscle would be expected. As skeletal muscle essentially cannot divide, hyperplasia would not be present. Because athleticism is considered normal stimulation of the musculature, the changes would be considered physiologic and not pathologic.

Answer: B (cardiac hypertrophy)

Explanation: given his past medical history of hypertension for 15 years, he is most likely to have some degree of cardiac hypertrophy. The cardiac myocytes essentially do not divide, so cardiac hyperplasia would not occur. While in some cases, cells within the lung can divide, pulmonary hyperplasia and pulmonary hypertrophy are not often described; also, with only a past medical history of hypertension, involvement of the lungs would not be likely.

Answer: B (β-myosin heavy chain)

Explanation: β-myosin heavy chain is the fetal form of the myosin heavy chain, and is more effective in its use of energy and slower in its contractions, and hence, in a hypertrophied heart, as would occur in a patient with hypertension, and as a 540 gram heart represents, would be in increased amount. The switch from the adult α-myosin heavy chain to the fetal β-myosin heavy chain represents the body’s adaptation to the increased stress placed on the heart by the systemic hypertension.

Answer: C (atrophy)

Explanation: Stenosis of the left femoral artery would cause ischemia of the down-stream musculature. Because the stenosis has developed slowly, the skeletal muscle cells would have a chance to adapt to the change; therefore, necrosis would not be expected. Skeletal muscle cells essentially do not divide, so hyperplasia could not occur–also, ischemia would decrease the amount of oxygen and nutrients available to the cells, so there would be no stimulus for hyperplasia or hypertrophy. Metaplasia does not occur in this context (i.e., there is not a better cell type that the skeletal muscle cells can switch to to better handle the decreased blood flow). The skeletal muscle cells would undergo atrophy.

Answer: D (pathologic endometrial hyperplasia)

Explanation: the elevated concentration of estrogen would promote division and proliferation of the endometrial glandular epithelium (hyperplasia). Because the stimulus for the proliferation is a tumor, the hyperplasia would be considered pathologic. Physiologic hyperplasia of the endometrium occurs during the proliferative phase of the menstrual cycle.

Answer: E (vascular stenosis)

Explanation: some of the skeletal myocytes are smaller than normal, hence the decreased size on cross section with the resultant more closely packed nuclei. This is atrophy. While in some way, each of the choices could potentially be associated with skeletal muscle atrophy (e.g., due to wasting, or nerve involvement), the only condition listed that could be consistently associated with atrophy of the skeletal muscle would be vascular stenosis, which would result in ischemia of the downstream tissue.

Answer: B (squamous metaplasia of the bronchi)

Explanation: due to prolonged exposure to the toxins in cigarette smoke, the lining of the trachea and bronchi can switch from respiratory type epithelium to squamous metaplasia, as the squamous metaplasia is better designed to handle such exposures. With no history of a condition producing elevated serum concentrations of calcium (e.g., parathyroid gland adenoma) metastatic calcification would not occur. While dystrophic calcification could be present as aged tissue is damaged to some extent and can calcify, it should not be extensive in distribution. Patients who smoke can develop chronic bronchitis, which would be associated with hyperplasia of submucosal glands. With no history of a neuromuscular condition predisposing to aspiration, chronic aspiration is very unlikely, also, if gastric metaplasia did occur in patients, it would be very rare to find.

Answer: A (abundant anthracotic pigment and focal squamous metaplasia)

Explanation: a patient with a long history of heavy cigarette use would be expected to have prominent amount of anthracotic pigment (i.e., carbonaceous pigment). In addition, with long term exposure to cigarette smoke, the respiratory epithelium can undergo squamous metaplasia. This process can lead to the development of a squamous cell carcinoma in the lung (i.e., one form of non-small cell carcinoma). Respiratory metaplasia does not occur, as the respiratory epithelium is the expected normal type of epithelium. Honey comb change can have respiratory epithelium, but this would be expected in a person with a history of interstitial lung disease. Steatosis is most commonly encountered in the liver, but also the heart and skeletal muscle, but essentially not in the lung. Russell bodies would be found in plasma cells, and plasma cells could be found in the lung in this case; however, the number of Russell bodies would not be prominent and scant anthracotic pigment would not be what was expected.

Answer: C (menstrual phase endometrium)

Explanation: apoptosis is an orderly destruction of a cell. During the menstrual cycle, the endometrium thickens in preparation for implantation; however, if implantation does not occur, the proliferated tissue must be removed. Apoptosis would allow for an orderly removal of tissue without promoting a significant inflammatory infiltrate. As a part of apoptosis, the nucleus is fragmented, and the DNA when run on a gel will then appear as numerous discrete bands whereas in necrosis, which is uncoordinated destruction of the nucleus, the DNA run on a gel would appear more as a smear.

Answer: C (healed bruise)

Explanation: the pigment described is hemosiderin, which accumulates due to the breakdown of red blood cells. A collection of hemosiderin would be associated with a healed bruise (due to the breakdown of red blood cells that would have accumulated at the site). While tattoo pigment can occur in the dermis, it would be more of a finely stippled black coloration, as would melanin, which would be finely stippled and brown to black in color. Lipofuscin, which is a finely stippled yellow-brown pigment, is associated with increasing age; however, the dermis is not a location where it is identified, instead it is commonly found in the heart, liver, and neurons. A parathyroid adenoma would be associated with metastatic calcification; however, deposits of calcium are basophilic.