Chapters 1-10

Question 1

A 38-year-old man has had headaches and nausea for the past 2 months. Laboratory findings show hypercalcemia and hypophosphatemia and normal serum albumin. Urine microscopic analysis shows deposition of calcium salts in the renal tubular epithelium. Which of the following processes has most likely produced this change in the kidney? • Dystrophic calcification • Renal tubular atrophy • Autophagocytosis • Metastatic calcification • Cellular aging

Answer 1

Metastatic calcification Deposition of calcium in normal healthy tissues as a result of prolonged hypercalcemia is called metastatic calcification. This process may occur in hyperparathyroidism. Dystrophic calcification refers to calcium deposition in injured tissues, with normal serum calcium levels. Atrophy decreases cell size but is not accompanied by calcium deposition. Autophagocytosis yields more golden-brown lipofuscin pigment in the cytoplasm, particularly in hepatocytes and myocardial fibers, a process that becomes more apparent with aging. See pages 38-39.

Question 2

An experiment introduces a “knockout” gene mutation into a cell line. The frequency of cell karyorrhexis and cytoplasmic fragmentation is increased, compared with a cell line without the mutation. Overall survival of the mutant cell line is reduced. Which of the following genes is most likely to be affected by this mutation? • BAX • BCL-2 • C-MYC • FAS • TP53

Answer 2

BCL-2 The BCL-2 gene product inhibits cellular apoptosis by binding to Apaf-1. The BAX gene product promotes apoptosis. The C-MYC gene is involved with oncogenesis. The FAS gene encodes for a cellular receptor for FAS ligand, which signals apoptosis. TP53 gene activity normally stimulates apoptosis, but mutation favors cell survival. See pages 28-29.

Question 3

A 43-year-old man has had a cough and fever for the past 2 months. A chest radiograph shows bilateral nodular densities, some with calcification, located mainly in the upper lobes of the lungs. A transbronchial lung biopsy is performed, yielding a specimen with the microscopic appearance shown. Which of the following chemical mediators is most important in the pathogenesis of this lesion? • Complement C5a • Interferon-γ • Bradykinin • Nitric oxide • Prostaglandin

Answer 3

Interferon-γ The figure shows a granuloma with many epithelioid cells and prominent large Langhans giant cells. Macrophage stimulation and transformation to epithelioid cells and giant cells are characteristic of granuloma formation. Interferon-γ promotes the formation of epithelioid cells and giant cells. Complement C5a is chemotactic for neutrophils. Although occasional neutrophils are seen in granulomas, neutrophils do not form a major component of granulomatous inflammation. Bradykinin, released in acute inflammatory responses, results in pain. Macrophages can release nitric oxide to destroy other cells, but nitric oxide does not stimulate macrophages to form a granulomatous response. Prostaglandins are mainly involved in the causation of vasodilation and pain in acute inflammatory responses. See pages 73-74.

Question 4

A 55-year-old woman has had discomfort and swelling of the left leg for the past week. On physical examination, the leg is slightly difficult to move, but on palpation, there is no pain. A venogram shows thrombosis of deep left leg veins. Which of the following mechanisms is most likely to cause this condition?

· Turbulent blood flow

· Nitric oxide release

· Ingestion of aspirin

· Hypercalcemia

· Immobilization

Answer 4

Immobilization

The most important and the most common cause of venous thrombosis is vascular stasis, which often occurs with immobilization. Turbulent blood flow may promote thrombosis, but this risk factor is more common in fast-flowing arterial circulation. Nitric oxide is a vasodilator and an inhibitor of platelet aggregation. Aspirin inhibits platelet function and limits thrombosis. Calcium is a cofactor in the coagulation pathway, but an increase in calcium has minimal effect on the coagulation process.
See pages 121-122.

Question 5

A 25-year-old woman with amenorrhea has never had menarche. On physical examination, she is 145 cm (4 ft, 9 in) tall. She has a webbed neck, a broad chest, and widely spaced nipples. Strong pulses are palpable in the upper extremities, but there are only weak pulses in the lower extremities. On an abdominal MR imaging, the ovaries are, the ovaries are small, elongated, and tubular. Which of the following karyotypes is most likely to be present in this patient?

· 45,X/46,XX

· 46,X,X(fra)

· 47,XXY

· 47,XXX

· 47,XX,+16

Answer 5

45,X/46,XX

The features described are those of classic Turner syndrome. Individuals who reach adulthood may have mosaic cell lines, with some 45,X cells and some 46,XX. A female carrier of the fragile X syndrome, X(fra), is less likely to manifest the disease than a male, but the number of triple repeat sequences (CGG) increases in her male offspring. The 47,XXY karyotype occurs in Klinefelter syndrome; affected individuals appear as phenotypic males. The “superfemale” karyotype (XXX) leads to mild.
See pages 165-167.

Question 6

A 10-year-old boy who is mentally retarded is able to carry out activities of daily living, including feeding and dressing himself. On physical examination, he has brachycephaly and oblique palpebral fissures with prominent epicanthal folds. A transverse crease is seen on the palm of each hand. On auscultation of the chest, there is a grade III/VI systolic murmur. Which of the following diseases is he most likely to develop by age 20?

· Acute leukemia

· Hepatic cirrhosis

· Chronic renal failure

· Acute myocardial infarction

· Aortic dissection

Answer 6

Acute leukemia

This boy has Down syndrome (trisomy 21), one of the trisomies that can result in a liveborn infant. Although children with Down syndrome can function fairly well, they often have many associated congenital anomalies. Among the more common is congenital heart disease, including ventricular septal defect. There is also a 10- to 20-fold increased risk of acute leukemia. Virtually all individuals with Down syndrome who live to the age of 40 will have evidence of Alzheimer disease. Hepatic cirrhosis is a feature of galactosemia. Chronic renal failure may be seen in genetic disorders that produce polycystic kidneys. Myocardial infarction at a young age suggests familial hypercholesterolemia. Aortic dissection is seen in persons with Marfan syndrome.
See [page:161] [pages 161-162].

Question 7

A 25-year-old woman gives birth to a term infant with a right transverse palmar crease, low-set ears, oblique palpebral fissures, and a heart murmur. The infant survives to childhood and exhibits only mild mental retardation. Which of the following chromosomal abnormalities is most likely to be present in this child?

· Haploidy

· Monosomy

· Mosaicism

· Tetraploidy

· Triploidy

Answer 7

Mosaicism

These features are characteristic of trisomy 21, but the child is not severely affected, which suggests mosaicism. In mosaic individuals, greater numbers of potentially normal cells having the proper chromosomal complement are present, which may allow infants with abnormalities of chromosome number to survive to term and beyond. Haploidy is present in gametes. Loss of an autosomal chromosome is devastating; the only monosomy associated with possible survival to term is Turner syndrome (monosomy X). Most aneuploid conditions (trisomies and monosomies) lead to fetal demise; fetuses with trisomy 21 are the most likely to survive to term. Triploid fetuses rarely survive beyond the second trimester and are virtually never liveborn. Likewise, tetraploidy accounts for many first-trimester fetal losses and is not survivable.
See [page:161] [pages 161-163].

Question 8

A 30-year-old woman has had fever and arthralgia for the past 2 weeks. On physical examination, she has a temperature of 37.6°C and an erythematous malar rash. Initial laboratory studies are positive for ANAs at 1:1600 and anti–double-stranded DNA antibodies at 1:3200. Serum creatinine is markedly elevated, and serum complement levels are decreased. A VDRL test for syphilis is positive, and in vitro tests of coagulation (prothrombin time and partial thromboplastin time) are prolonged. Which of the following clinical features of her illness is most likely caused by antibodies that interfere with the coagulation test?

· Arthritis

· Recurrent thrombosis

· Rash

· Renal failure

· Fever

Answer 8

Recurrent thrombosis

This patient has clinical and serologic features of systemic lupus erythematosus (SLE). She also has a false-positive test result for syphilis, indicating the presence of anticardiolipin antibodies. These antibodies against phospholipid-protein complexes (antiphospholipid antibodies) are also called lupus anticoagulants, because they interfere with in vitro clotting tests. However, in vivo, they are thrombogenic. Hence, these patients can have recurrent thrombosis. Lupus anticoagulants can also occur in the absence of lupus. The other listed options can occur in SLE, but they are not mediated by antiphospholipid antibodies.
See pages 213-221.

Question 9

A 37-year-old man who is HIV positive has noticed multiple 0.5- to 1.2-cm, plaque-like, reddish-purple skin lesions on his face, trunk, and extremities. Some of the larger lesions appear to be nodular. These lesions have appeared over the past 6 months and have slowly enlarged. Molecular analysis of the spindle cells found in these skin lesions is likely to reveal the genome of which of the following viruses?

· Cytomegalovirus

· Epstein-Barr virus

· Adenovirus

· Human herpesvirus-8

· HIV-1

Answer 9

Human herpesvirus-8

This patient has AIDS, with Kaposi sarcoma of the skin. Kaposi sarcoma is associated with a herpesvirus agent that is sexually transmitted: human herpesvirus 8 (HHV-8), also called the Kaposi sarcoma herpesvirus. Other herpesviruses are not involved in the pathogenesis of Kaposi sarcoma, although infection with these viruses can occur frequently in persons with AIDS. HIV, although present in the lymphocytes and monocytes, is not detected in the spindle cells that proliferate in Kaposi sarcoma. With the exception of the varicella-zoster virus, which is associated with dermatomally distributed skin vesicles known as shingles, skin lesions are not common manifestations of herpesviruses, which include cytomegalovirus, Epstein-Barr virus, or adenovirus infections.
See pages 246-247.

Question 10

A 45-year-old woman has experienced difficulty in swallowing that has increased in severity over the past year. She has also experienced malabsorption, demonstrated by a 5-kg weight loss in the past 6 months. She reports increasing dyspnea during this time. On physical examination, her temperature is 36.9°C, pulse 66/min, respirations 18/min, and blood pressure 145/90 mm Hg. Echocardiography shows a large pericardial effusion. The ANA test result is positive at 1:512 with a nucleolar pattern. Which of the following serious complications of the patient’s underlying autoimmune disease is most likely to occur?

· Meningitis

· Glomerulonephritis

· Perforated duodenal ulcer

· Adrenal failure

· Malignant hypertension

Answer 10

Malignant hypertension

This patient has diffuse systemic sclerosis (scleroderma). The small arteries of the kidney are damaged by a hyperplastic arteriolosclerosis that can be complicated by very high blood pressure and renal failure. Meningitis and adrenal failure are not typical features of autoimmune diseases. Glomerulonephritis is a more typical complication of systemic lupus erythematosus. With scleroderma, the gastrointestinal tract undergoes fibrosis, without any tendency to perforation or ulceration.
See pages 223-225.

Question 11

An epidemiologic study is conducted to determine risk factors for HIV infection. The study documents that persons with coexisting sexually transmitted diseases such as chancroid are more likely to become HIV positive. It is postulated that an inflamed mucosal surface is an ideal location for the transmission of HIV during sexual intercourse. Which of the following cells in these mucosal surfaces is most instrumental in transmitting HIV to CD4+ T lymphocytes?

· CD8+ cells

· Natural killer cells

· Dendritic cells

· Neutrophils

· Plasma cells

Answer 11

Dendritic cells

Three types of cells can carry HIV: dendritic cells, monocytes, and CD4+ T cells. Mucosal dendritic cells (i.e., Langerhans cells) can bind to the virus and transport it to CD4+ cells in the lymph nodes. Whether the virus is internalized by mucosal dendritic cells is not clear. Monocytes and CD4+ T cells express CD4 and the coreceptors (CCR5 and CXCR4); therefore, HIV can enter these cells. Follicular dendritic cells are distinct from mucosal or epithelial dendritic cells; they trap antibody-coated HIV virions by means of their Fc receptors. The other listed cells cannot be infected by HIV.
See pages 238-243.

Question 12

A 26-year-old woman has had bouts of joint pain for the past 2 years. She also has a rash on the cheeks and bridge of the nose. On physical examination, there is no joint swelling or deformity, although generalized lymphadenopathy is present. Laboratory studies indicate anemia, leukopenia, a polyclonal gammopathy, and proteinuria. The serum ANA test result is positive at a titer of 1:1024 with a rim pattern identified by immunofluorescence. The light microscopic and immunofluorescent (with antibody to IgG) appearances of a skin biopsy are shown. Which of the following is the best information to give this patient about her disease?

· Blindness is likely to occur within 5 years

· Avoid exposure to cold environments

· Joint deformities will eventually occur

· Chronic renal failure is likely to occur

· Cardiac valve replacement will eventually be required

Answer 12

Chronic renal failure is likely to occur

This patient has systemic lupus erythematosus (SLE). Many persons with SLE have glomerulonephritis and eventually develop renal failure. Blindness is uncommon in SLE. Raynaud phenomenon is associated with many autoimmune diseases, but it is most troublesome in scleroderma. Although synovial inflammation is common in SLE, joint deformity is rare. The Libman-Sacks endocarditis associated with SLE tends to be nondeforming and limited, and there is minimal valve damage. It is now uncommon, because of the use of corticosteroid therapy in the treatment of SLE.
See pages 213-221.

Question 13

A 9-month-old child has a history of recurrent infections with multiple agents, including cytomegalovirus, Candida albicans, Staphylococcus aureus, and Staphylococcus epidermidis. A careful family history and pedigree analysis show this to be a genetic disorder that is inherited in an autosomal recessive pattern. Which of the following laboratory studies is likely to be most useful in establishing the underlying mechanism of immunodeficiency in this infant?

· Quantitative serum immunoglobulin levels

· Enumeration of B cells in blood

· Enumeration of CD3+ cells in blood

· Tests of neutrophil function

· Adenosine deaminase levels in leukocytes

Answer 13

Adenosine deaminase levels in leukocytes

This patient is susceptible to bacterial, fungal, and viral infections and most likely has severe combined immunodeficiency (SCID). The autosomal recessive pattern of inheritance implicates adenosine deaminase (ADA) deficiency rather than mutations in the γ chain of cytokine receptors. Low ADA levels in the leukocytes are diagnostic. The other listed options are relevant to the workup of primary immunodeficiencies, but they are not specific to SCID.
See pages 234-235.

Question 14

A 28-year-old man has had hemoptysis and hematuria for the past 2 days. On physical examination, his temperature is 36.8°C, pulse 87/min, respirations 19/min, and blood pressure 150/90 mm Hg. Laboratory studies show creatinine of 3.8 mg/dL and urea nitrogen of 35 mg/dL. Urinalysis shows 4+ hematuria, 2+ proteinuria, and no glucose. A renal biopsy specimen examined microscopically shows glomerular damage and linear immunofluorescence with labeled anti-complement and anti-IgG antibody. Which of the following autoantibodies has the greatest specificity for this patient’s condition?

· Anti–double-stranded DNA

· Antihistone

· Anti–Jo-1

· Anti–U1-riboneucleoprotein

· Anti–SS-A

· Anti–basement membrane

· Anti-phospholipid

Answer 14

Anti–basement membrane

This patient has Goodpasture syndrome, in which an antibody is directed against type IV collagen in basement membranes of the glomeruli and in the lung. This is a form of type II hypersensitivity reaction. The antibodies attach to the basement membrane and fix complement, thus damaging the glomeruli. Anti–double-stranded DNA antibodies have specificity for systemic lupus erythematosus (SLE), whereas antihistone antibodies are characteristic of drug-induced SLE. Anti–Jo-1 antibody is found in dermatomyositis and polymyositis. The anti-U1-ribonucleoprotein antibody is seen in mixed connective tissue diseases. Anti–SS-A antibody is seen in Sjögren syndrome. Antiphospholipid antibodies are sometimes called “lupus anticoagulant,” because they may appear in SLE; such patients have coagulopathies with thrombosis or bleeding, or both. See pages 201, 203.

Question 15

A 61-year-old man has had increasing malaise for the past 4 months. On physical examination, he is afebrile and has mild muscle wasting. Laboratory studies show serum creatinine of 4.5 mg/dL and urea nitrogen of 44 mg/dL. Urine dipstick analysis shows no blood, protein, or glucose, but a specific test for Bence Jones proteins yields a positive result. A renal biopsy specimen has the microscopic appearance shown in the figure. Which of the following underlying conditions is most likely to be present in this patient?

· Rheumatic fever

· Multiple myeloma

· Ankylosing spondylitis

· Systemic sclerosis

· Common variable immunodeficiency

Answer 15

Multiple myeloma

Amyloidosis is most often caused by excessive light chain production with plasma cell dyscrasias such as multiple myeloma (AL amyloid). Chronic inflammatory conditions, such as rheumatic fever, ankylosing spondylitis, and systemic sclerosis, may also result in amyloidosis (AA amyloid), but not in secretion of light chains in urine (i.e., Bence Jones proteinuria). Immunoglobulin levels are generally reduced in patients with common variable immunodeficiency. See pages 252-253.

Question 16

A 66-year-old woman sees her physician because of a lump on the right side of the neck that has been increasing in size for the past 7 months. On physical examination, the physician palpates a firm but nontender 3-cm mass in the posterior cervical lymph node. Microscopic examination of a biopsy specimen of the mass shows effacement of the nodal architecture by a monomorphous population of large cells with large, dark blue nuclei and scant cytoplasm. The peripheral blood smear and bone marrow biopsy results are normal. Which of the following is the most likely diagnosis?

· Lymphangioma

· Reactive hyperplasia

· Non-Hodgkin lymphoma

· Multiple myeloma

· Chronic myelogeous leukemia

Answer 16

Non-Hodgkin lymphoma

Non-Hodgkin lymphomas are malignant neoplasms of lymphoid tissues. They have no benign equivalent. Monomorphous proliferations that destroy the nodal architecture suggest a neoplasm. A lymphangioma is composed mostly of a proliferation of lymphatics. Reactive hyperplasias are polyclonal, controlled proliferations with a diverse cell population. A myeloma is composed of plasma cells and most often involves bone marrow. A leukemia is a neoplasm that arises in the bone marrow and spills over into peripheral blood.
See page 263.

Question 17

During a routine health maintenance examination, a 46-year-old man is found to have an enlarged, nontender supraclavicular lymph node that is palpable on physical examination. The 2-cm node is excised. Histologically, the nodal architecture is effaced by a monomorphous population of small lymphocytes. Which of the following procedures would best confirm that the patient has a malignancy?

· Peripheral WBC count and differential cell count

· Flow cytometry of nodal tissue for DNA content

· Electron microscopy to determine cellular ultrastructure

· Southern blot analysis to demonstrate monoclonality

· Determination of the serum lactate dehydrogenase level

Answer 17

Southern blot analysis to demonstrate monoclonality

Monoclonality is the hallmark of a malignancy. In the diagnosis of a leukemia, the WBC count is helpful but not definitive. The DNA content analysis alone cannot define a malignancy; Southern blot analysis for T- or B-cell receptor gene rearrangements can define monoclonality. Electron microscopy is an adjunct to diagnosis of the type of tumor. Lactate dehydrogenase levels are often increased with lymphoid proliferations but are not diagnostic of the type of proliferation.
See pages 278, 324-327.

Question 18

An epidemiologic study is performed to assess risks for cervical carcinoma. The cells from cervical lesions in a population of women are analyzed, and there is viral binding to pRB in patients in whom dysplastic cells are present. Which of the following viruses is most likely to bind to pRB to increase the risk for these lesions?

· Cytomegalovirus

· Epstein-Barr virus

· Herpes simplex virus

· Hepatitis B virus

· HIV

· Human papillomavirus

· JC papovavirus

Answer 18

Human papillomavirus

Human papillomavirus (HPV) types 16, 18, and 31 encode proteins that bind TP53 with high affinity, resulting in loss of tumor suppressor activity. Seventy-five to nearly 100% of squamous epithelial dysplasias and carcinomas of the cervix are associated with HPV infection. Cytomegalovirus and herpes simplex virus do not participate directly in carcinogenesis. Epstein-Barr virus is associated with some malignant lymphomas and nasopharyngeal carcinomas. Hepatitis B virus is associated with hepatocellular carcinomas arising in the setting of regeneration in chronic liver injury. HIV does not affect pRB, but the loss of immune regulation promotes development of lymphomas and Kaposi sarcoma. The JC papovavirus is associated with development of progressive multifocal leukoencephalopathy.
See pages 313-314.

Question 19

A 23-year-old woman has noted a nodule on the skin of her upper chest. She reports that the nodule has been present for many years and has not changed in size. On physical examination, there is a 0.5-cm dark-red, nontender, raised nodule with a smooth surface. Which of the following is the most likely diagnosis?

· Adenoma

· Fibroadenoma

· Hamartoma

· Hemangioma

· Leiomyoma

· Lipoma

· Melanoma

· Nevus

Answer 19

Hemangioma

The small, discrete nature of this mass and its relatively unchanged size suggest a benign neoplasm. The red color suggests vascularity. A hemangioma is a common benign lesion of the skin. Adenomas arise in glandular epithelium, such as the colon. Fibroadenomas arise in the breast. A hamartoma contains a mixture of cell types common to a tissue site. Leiomyomas, which are white, arise from smooth muscle and are most common in the uterus. Lipomas are yellow fatty tumors. Melanomas are malignant and tend to increase in size quickly; many are darkly pigmented. The benign counterpart to the melanoma is the nevus, which is quite common; nevi are usually light brown. See pages 260-262.

Question 20

A 70-year-old man has sprayed his orchard with insecticide each spring for 20 years. He recently noticed a rough, erythematous area of skin on the right shoulder. The patch becomes ulcerated and does not heal. He develops weight loss, nausea, and vomiting. The excised lesion is a squamous cell carcinoma. Which of the following was most likely a component of the insecticide that was used by this man?

· Arsenic

· Benzene

· Cadmium

· Chromium

· Chlorinated biphenyl

· Ethylene oxide

· Naphthalene

Answer 20

Arsenic

Arsenic can cause skin cancer. However, lead arsenate has not been in widespread use for years, and occupational safety measures have reduced risks to workers from the use of chemicals in agriculture and industry. Benzene is linked to leukemias. Cadmium exposure is linked to prostate cancer (dispose of old batteries properly!). Some lung cancers are linked to chromium exposure. Chlorinated biphenyls, contained in many insect sprays, have not been linked directly to cancer. Ethylene oxide exposure carries an increased risk of leukemia. Ethylene oxide has been employed as a ripening agent for some agricultural products, and it is also used as a disinfectant gas for surgical equipment in hospitals. Exposure to naphthalene compounds is a risk factor for urinary tract cancer. See pages 274, 309-311.

Question 21

A 38-year-old woman has abdominal distention that has been worsening for the past 6 weeks. An abdominal CT scan shows bowel obstruction caused by a 6-cm mass in the jejunum. At laparotomy, a portion of the small bowel is resected. Microscopic examination shows that the mass is a Burkitt lymphoma. Flow cytometry analysis of a portion of the tumor shows a high S phase. Mutational activation of which of the following nuclear oncogenes is most likely to be present in this tumor?

· ERBB2

· TP53

· RAS

· MYC

· APC

Answer 21

MYC

The MYC oncogene is commonly activated in Burkitt lymphoma because of a t(8;14) translocation. The MYC gene binds DNA to cause transcriptional activation of growth-related genes such as that for cyclin D1, resulting in activation of the cell cycle. ERBB2 (also known asHER2) encodes growth factor receptor located on the cell surface. TP53 and APC are tumor suppressor genes that are inactivated in many cancers, including colon cancer (APC). RASoncogene encodes a GTP-binding protein that is located under the cell membrane.
See page 284.

Question 22

A 33-year-old woman undergoes a routine physical examination as part of her health maintenance screening. There are no abnormal findings. A Pap smear is obtained as part of the pelvic examination. Cytologically, the cells obtained on the smear from the cervix show severe epithelial dysplasia. Which of the following statements best explains the significance of these findings?

· The lesion could progress to invasive cervical carcinoma

· An ovarian teratoma is present

· There has been regression of a cervical carcinoma

· Antibiotic therapy will cure the lesion

· Female relatives are at risk of acquiring the same condition

Answer 22

The lesion could progress to invasive cervical carcinoma

Epithelial dysplasias, especially those that are severe, can be precursors of carcinomas. This is a key reason for Pap smear screening; the incidence of cervical carcinoma decreases when routine Pap smears are performed. Teratomas show well-differentiated elements derived from all the germ cell layers, and they do not manifest as epithelial dysplasias. Severe dysplasias are not amenable to antibiotic therapy. Cervical dysplasias are not hereditary. Regression of a malignancy is a rare event.
See pages 271-273.

Question 23

A 25-year-old soldier stationed in the Middle East has experienced abdominal enlargement and a 7-kg weight loss over the past 7 weeks. On physical examination, there is hyperpigmentation of skin, hepatosplenomegaly, and generalized lymphadenopathy. Laboratory studies show hemoglobin of 10.0 g/dL, hematocrit 29.9%, platelet count 78,200/mm3, and WBC count 3210/mm3. One month later, he develops a high fever, and Streptococcus pneumoniae is cultured from his blood. Which of the following infectious organisms is most likely to produce these findings?

· Borrelia recurrentis

· Brugia malayi

· Leishmania donovani

· Listeria monocytogenes

· Mycobacterium leprae

· Plasmodium falciparum

· Trypanosoma gambiense

Answer 23

Leishmania donovani

This patient has visceral leishmaniasis, or kala-azar. Leishmaniasis is endemic in the Middle East, South Asia, Africa, and Latin America. The organisms proliferate within macrophages in the mononuclear phagocyte system and cause hepatosplenomegaly and lymphadenopathy. Often, there is hyperpigmentation of the skin. Bone marrow involvement and splenic enlargement contribute to reduced production and accelerated destruction of hematopoietic cells, giving rise to pancytopenia. Borreliosis causes relapsing fever and is transmitted via body lice. Brugia malayi is a nematode transmitted by mosquitoes that leads to filariasis involving lymphatics to produce elephantiasis. Leishmania donovani is transmitted by sand flies and leads to infection of macrophages, which produces hepatosplenomegaly, lymphadenopathy, and bone marrow involvement with pancytopenia. Listeriosis is most often acquired via contaminated food or water. In most adults, it produces mild diarrheal illness, but in some adults and children, and in fetuses, it may produce meningitis or dissemination with microabscess (microgranuloma) formation. Mycobacterium leprae causes Hansen disease, with infection of peripheral nerves and skin. In persons with a strong immune response, the tuberculoid form of this disease results in granuloma formation; in those with a weak immune response, the lepromatous form occurs, characterized by large numbers of macrophages filled with short, thin, acid-fast bacilli. Malaria, caused by Plasmodium falciparum, produces hemolytic anemia, splenomegaly, and cerebral thrombosis. African trypanosomiasis produces sleeping sickness.
See pages 388-390.

Question 24

A 31-year-old man has had increasing respiratory difficulty for the past 2 days. On physical examination, crackles are auscultated over all lung fields. A chest radiograph shows bilateral interstitial infiltrates. Laboratory studies show that the patient is HIV positive and has a plasma titer of 26,800 copies of HIV-1 RNA/mL. A transbronchial biopsy is performed, and the microscopic appearance of the specimen is shown. On the basis of the clinical and histologic findings, which of the following is the most likely causative organism of this acute illness?

· Epstein-Barr virus

· Cytomegalovirus

· Respiratory syncytial virus

· Herpes zoster virus

· Adenovirus

Answer 24

Cytomegalovirus

This patient has high HIV-1 RNA levels that are consistent with the diagnosis of AIDS. Although patients with AIDS are susceptible to many microbes, infections with cytomegalovirus (CMV) are particularly common. The biopsy specimen shows an enlarged cell containing a distinct intranuclear inclusion and ill-defined cytoplasmic inclusions, which are typical of CMV infection. Epstein-Barr virus infection frequently is seen in patients with HIV infection, but there are no distinct pulmonary lesions associated with it. Respiratory syncytial virus infections are seen in children but rarely in adults. Herpes zoster infections are most likely to affect the peripheral nervous system, rarely can become disseminated to affect the lungs in immunosuppressed patients, and produce a different appearance than that shown. Adenovirus is a common viral pathogen in adults that may produce a clinically significant pneumonia, and intranuclear inclusions may be present, but the cells are not large, and cytoplasmic inclusions are absent.
See pages 353-355.

Question 25

A 60-year-old man has had persistent bloody diarrhea, abdominal cramps, and fever for the past week. On physical examination, his temperature is 38.1°C. He has mild diffuse abdominal pain. A stool sample is positive for occult blood. Sigmoidoscopic examination shows mucosal ulceration in the cecum and ascending colon. Microscopic examination of a colonic biopsy specimen shows flask-shaped mucosal ulcers with extensive necrosis and a modest, nonspecific, inflammatory response. The ulcers do not penetrate the muscularis propria. Which of the following infectious organisms is most likely to produce these findings?

· Giardia lamblia

· Entamoeba histolytica

· Shigella flexneri

· Salmonella enteritidis

· Vibrio cholerae

· Bacillus cereus

Answer 25

Entamoeba histolytica

Amebiasis is a common cause of dysentery in developing nations. The Entamoeba histolyticatrophozoites can attach to colonic epithelium, invade, and lyse the epithelial cells. In some cases, there can be extensive mucosal involvement with characteristic flask-shaped (like an Erlenmeyer flask) ulcerations similar to those seen in other severe inflammatory bowel diseases. Giardiasis tends to involve the small intestine and produces variable inflammation but not ulceration. Shigellosis can produce bloody dysentery with irregular superficial colonic mucosal ulceration, but the organisms typically do not invade beyond the lamina propria. Salmonellosis more typically involves the small intestine and in most cases produces self-limited enteritis, although more severe disease with dissemination to other organs can occur with Salmonella typhi infection. Cholera is characterized by massive, secretory diarrhea without intestinal mucosal invasion or necrosis. Bacillus cereus is a cause of food poisoning (most often as a contaminant in reheated fried rice) and has a short incubation time.
See pages 805-807.

Question 26

For the past 3 days, a 68-year-old woman has had a fever and a cough productive of yellow sputum. On physical examination, there is dullness to percussion at the left lung base. A chest radiograph shows areas of consolidation in the left lower lobe. Despite antibiotic therapy, the course of the disease is complicated by abscess formation, and she dies. At autopsy, there is a bronchopleural fistula surrounded by a pronounced fibroblastic reaction. Small, yellow, 1- to 2-mm “sulfur granules” are grossly visible within the area of abscess formation. Which of the following organisms is most likely to produce these autopsy findings?

· Actinomyces israelii

· Blastomyces dermatitidis

· Chlamydia pneumoniae

· Klebsiella pneumoniae

· Mycobacterium kansasii

Answer 26

Actinomyces israelii

Actinomycetes that can produce chronic abscessing pneumonia, particularly in immunocompromised patients, include Actinomyces israelii and Nocardia asteroides. Sulfur granules, formed from masses of the branching, filamentous organisms, are more likely to be seen in Actinomyces. Blastomyces dermatitidis infections tend to produce a granulomatous inflammatory process. Chlamydial infections produce an interstitial pattern like that of most viruses. Klebsiella infections, like other bacterial infections, can result in abscess formation, although without distinct sulfur granules. Mycobacterium kansasii infections are similar to M. tuberculosis infections in that granulomatous inflammation is prominent.
See pages 358, 363, 710-711.

Question 27

A 24-year-old college student comes to the health service because he has had a cough, fever, and shortness of breath for the past 3 weeks when walking. The results of cardiac examination are normal, but crackles are heard in both lungs. A chest radiograph shows patchy infiltrates in the lungs. Laboratory studies show an elevated cold agglutinin titer. A presumptive clinical diagnosis ofMycoplasma pneumoniae is made, and the patient responds to erythromycin therapy. Which of the following histologic changes is most likely responsible for the pulmonary symptoms in this patient?

· Neutrophils within bronchioles, extending into alveoli

· Granulomas with Langhans giant cells

· Pulmonary infarcts with vascular occlusion by microorganisms

· Mononuclear interstitial infiltrate

· Collection of neutrophils and fibrin in the pleural space

Answer 27

Mononuclear interstitial infiltrate

Mycoplasma infections lead to a primary atypical pneumonia in which there are no alveolar infiltrates, but there is prominent interstitial inflammation with lymphocytes, histiocytes, and plasma cells. Alveolar and bronchiolar neutrophilic exudates suggest a bacterial agent causing pneumonia. Granulomas with Langhans-type giant cells are typical of tuberculosis. Proliferation of microorganisms with vascular occlusion and infarction is most typical of Aspergillus fungal infections. An empyema with neutrophils suggests a bacterial cause for pneumonia with spread to pleura. See pages 714-716.

Question 28

A study of transfusion-related infectious diseases determines that some blood donors appear to have acquired an infection via vertical transmission from mother to child. Laboratory testing strategies are devised to detect the most common of these infections and exclude such persons as blood donors. As a consequence, which of the following infectious agents is most likely to be a significant cause for rejection as a blood donor later in life?

· Escherichia coli

· Hepatitis B virus

· Plasmodium vivax

· Candida albicans

Pneumocystis carinii

Answer 28

Hepatitis B virus

Testing for hepatitis B and C is part of routine screening of blood donors. This form of transmission for hepatitis B is most common in developing nations. Escherichia coli can be a congenital infection, but it leaves no major significant lasting sequelae in infants who survive. Malaria, candidal infection, and pneumocystosis are not congenital infections.
See pages 355.

Question 29

A 6-year-old boy has had diarrhea for 7 days and is brought to the physician. He has averaged about six stools per day, which appear mucoid and sometimes blood-tinged. On physical examination, his temperature is 37.4°C. He has mild lower abdominal tenderness but no masses. A stool culture is positive for Shigella sonnei. Which of the following would most likely be seen in an endoscopic biopsy specimen from this child’s colon?

· Epithelial disruption with overlying exudate of polymorphonuclear leukocytes (neutrophils)

· Multiple granulomas throughout the colon wall

· Slight increase in numbers of lymphocytes and plasma cells in lamina propria

· Intranuclear inclusions in enterocytes

· Extensive scarring of lamina propria with structure formation

Answer 29

Epithelial disruption with overlying exudate of polymorphonuclear leukocytes (neutrophils)

Shigellosis results in bloody dysentery because the Shigella organisms can invade and destroy the mucosa. There is typically a mononuclear infiltrate extending to the lamina propria, with a neutrophilic exudate overlying the ulcerated areas. Granulomatous inflammation may be seen with granulomatous colitis (Crohn disease) and intestinal tuberculosis (rare). An increase in mononuclear inflammatory cells may be seen with milder forms of enterocolitis caused by viruses, Giardia, and Salmonella spp. Intranuclear inclusions in enterocytes point to infection with DNA viruses, such as herpesviruses. Stricture formation may follow intestinal tuberculosis.
See pages 800-801.

Question 30

A 3-year-old child has erosion of a roughened corneal surface caused by xerophthalmia. Keratomalacia results in corneal scarring with eventual blindness after several years. This ocular damage could most likely have been prevented by treating a dietary deficiency of which of the following nutrients?

· Protein

· Vitamin K

· Iron

· Niacin

· Vitamin A

Answer 30

Vitamin A

Vitamin A is essential to maintain epithelia. The lack of vitamin A affects the function of lacrimal glands and conjunctival epithelium, promoting keratomalacia. Dietary protein is essential for building tissues, particularly muscle, but it has no specific effect in maintaining ocular structures. Vitamin K is beneficial for synthesis of coagulation factors by the liver to prevent bleeding problems. Iron is essential for production of heme, which is needed to manufacture hemoglobin in RBCs. Niacin is involved with nicotinamide in many metabolic pathways, and deficiency leads to diarrhea, dermatitis, and dementia. See pages 430-433.

Question 31

A 5-year-old child is admitted to the hospital after ingesting pills he found in a cabinet at home. The child is rapidly becoming obtunded. Laboratory studies show a serum AST level of 850 U/L and ALT level of 1052 U/L. The child’s respiratory and cardiac status remain stable. Which of the following drugs was most likely ingested?

· Acetaminophen

· Penicillin

· Aspirin

· Sulfamethoxazole

· Codeine

Answer 31

Acetaminophen

Acetaminophen toxicity produces hepatic necrosis. This effect is enhanced with prior ethanol ingestion. Hepatic necrosis is indicated by extremely high levels of AST and ALT. Penicillin can cause systemic anaphylaxis in a few persons. Aspirin can produce a metabolic acidosis. Sulfa drugs may produce renal failure. Opiates, including codeine, are central nervous system and respiratory depressants. See pages 416-417.

Question 32

A 23-year-old woman is delivered of a stillborn fetus at 36 weeks’ gestation. The woman experienced sudden onset of lower abdominal pain several hours before delivery. An abdominal ultrasound scan showed a large retroplacental hemorrhage. Delivery was accompanied by a 1200-mL blood loss. Maternal use of which of the following agents is most likely to be associated with these findings?

· Acetaminophen

· Amphetamine

· Cannabinoids

· Cocaine

· Ethanol

· Heroin

· Lysergic acid

Answer 32

Cocaine

Cocaine has powerful vasoactive effects, including vasoconstriction. The effects on the placenta can include decreased blood flow with fetal hypoxia and spontaneous abortion, placentae abruption, and fetal hemorrhages. Chronic maternal cocaine use results in neurologic impairment of infants. Acetaminophen overdosage can produce hepatic necrosis and encephalopathy. Amphetamines may have acute cardiovascular effects, including arrhythmias. Cannabinoids act as mild tranquilizers and have no major tissue effects. Ethanol ingestion in pregnancy can be associated with fetal alcohol syndrome, which is not fatal but results in subtle anomalies and impaired development. Heroin ingestion can lead to fetal cardiorespiratory depression but not hemorrhage. Lysergic acid (LSD) use does not cause hemorrhage.
See pages 417-418.

Question 33

A 49-year-old man has had increasing knee and hip pain for the past 10 years. The pain is worse at the end of the day. During the past year, he has become increasingly drowsy at work. His wife complains that he is a “world class” snorer. During the past month, he has experienced bouts of sharp, colicky, right upper abdominal pain. On physical examination, his temperature is 37°C, pulse 82/min, respirations 10/min, and blood pressure 140/85 mm Hg. He is 175 cm (5 ft 8 in) tall and weighs 156 kg (BMI 51). Laboratory findings show glucose of 139 mg/dL, total cholesterol 229 mg/dL, and HDL cholesterol 33 mg/dL. An arterial blood gas measurement shows pH of 7.3, PCO2 50 mm Hg, and PO2 70 mm Hg. Which of the following conditions is most likely to be present?

· Hashimoto thyroiditis

· Hypertrophic cardiomyopathy

· Laryngeal papillomatosis

· Nonalcoholic steatohepatitis

· Panlobular emphysema

· Rheumatoid arthritis

Answer 33

Nonalcoholic steatohepatitis

This patient is morbidly obese with complications, including obesity hypoventilation syndrome, glucose intolerance, probable sleep apnea, cholelithiasis, and osteoarthritis. Macrovesicular steatosis with hepatomegaly is seen in obesity and may even progress to cirrhosis. Weight gain due to hypothyroidism, which could occur in Hashimoto thyroiditis, is modest and does not lead to morbid obesity. An “obesity cardiomyopathy” resembles dilated cardiomyopathy. Laryngeal papillomatosis, which produces airway obstruction (without snoring), occurs more often in children and is not associated with obesity. The blood gas findings in this case could be seen in emphysema, which is not a complication of obesity; panlobular emphysema is much less common than the centrilobular emphysema associated with smoking. Rheumatoid arthritis tends to involve small joints first, and there is no relationship to obesity. See pages 438-443, 683.

Question 34

A 56-year-old man has had increasing lower leg swelling during the past 6 months. He also has had so much difficulty breathing at night that he sleeps propped up on two pillows. On physical examination, his temperature is 37.1°C, pulse 80/min, respirations 17/min, and blood pressure 110/70 mm Hg. On auscultation of the chest, bilateral crackles are audible at the lung bases. The liver span is increased. There is 2+ pitting edema to the thighs. Laboratory findings show hemoglobin of 13.4 g/dL, hematocrit 40.2%, MCV 88 μm3, platelet count 229,300/mm3, and WBC count 6715/mm3. One year later, he develops an acute psychosis. He dies of aspiration pneumonia. At autopsy, there is anterior vermian atrophy and petechial hemorrhages with brown discoloration in the periaqueductal gray matter, as well as shrunken mamillary bodies. A chronic deficiency of which of the following vitamins is most likely to explain these findings?

· Vitamin A (retinoic acid)

· Vitamin B1 (thiamine)

· Vitamin B2 (riboflavin)

· Vitamin B3 (niacin)

· Vitamin B12 (cobalamin)

· Vitamin C (ascorbic acid)

· Vitamin D (cholecalciferol)

· Vitamin E (α-tocopherol)

Answer 34

Vitamin B1 (thiamine)

The patient has features of Wernicke disease and beriberi, both resulting from thiamine deficiency, which can accompany chronic alcoholism. Vitamin A deficiency leads to night blindness, keratomalacia, and respiratory tract difficulties due to epithelial disorders. Pure vitamin B2 deficiency is rare and is marked by findings such as neuropathy and cheilosis. Niacin deficiency leads to pellagra with dementia, diarrhea, and photodermatitis. Vitamin B12deficiency leads to subacute combined degeneration of the spinal cord; the MCV in this case is not in the range to cause macrocytosis. Vitamin C deficiency leads to scurvy with anemia, loose teeth, hematomas, and poor wound healing. Vitamin D deficiency in an adult leads to osteomalacia with risk of fractures. Vitamin E deficiency is rare and produces spinal cord changes similar to those of vitamin B12 deficiency. See pages 412-414, 438, 1328.

Question 35

A 3-month-old previously healthy infant was found dead by his mother late one evening. When she put him in his crib 1 hour earlier, he showed no signs of distress. The infant’s term birth had followed an uncomplicated pregnancy, and he had been feeding well and gaining weight normally. Which of the following is the medical examiner most likely to find at autopsy?

· Hyaline membrane disease

· Cerebral cytomegalovirus

· Tetralogy of Fallot

· Adrenal neuroblastoma

· No abnormalities

Answer 35

No abnormalities

The events described suggest sudden infant death syndrome (SIDS). The cause is unknown and, by definition, there are no significant gross or microscopic autopsy findings. Infants with congenital anomalies or infections are unlikely to appear healthy, feed well, or gain weight normally. Hyaline membrane disease occurs at birth with prematurity. Congenital neoplasms are a rare cause of sudden death. See pages 495-497.

Question 36

A 19-year-old woman, G 2, P 1, has a screening ultrasound at 20 weeks’ gestation that shows no abnormalities. However, premature labor leads to an emergent vaginal delivery at 31 weeks. Soon after birth, the neonate develops respiratory distress requiring intubation with positive pressure ventilation. Which of the following prenatal diagnostic tests could have best predicted this neonate’s respiratory distress?

· Maternal serum α-fetoprotein determination

· Phospholipid analysis of amniotic fluid

· Chromosomal analysis

· Coombs test on cord blood

· Genetic analysis for cystic fibrosis gene

Answer 36

Phospholipid analysis of amniotic fluid

The neonate most likely has hyaline membrane disease from fetal lung immaturity and lack of surfactant. Surfactant consists predominantly of dipalmitoyl phosphatidylcholine. The adequacy of surfactant production can be gauged by the phospholipid content of amniotic fluid, because fetal lung secretions are discharged into the amniotic fluid. The maternal serum α-fetoprotein level is useful to predict fetal neural tube defects and chromosomal abnormalities. Chromosomal analysis may help to predict problems after birth or the possibility of fetal loss. The Coombs test may help to determine the presence of erythroblastosis fetalis. Cystic fibrosis does not cause respiratory problems at birth. See pages 456-458.

Question 37

A 19-year-old primigravida who has had an uncomplicated pregnancy undergoes a screening ultrasound at 16 weeks’ gestation that shows no abnormalities. At 18 weeks, the woman develops a mild rash on her face. She gives birth to a stillborn severely hydropic male infant at 33 weeks. At autopsy, there are no congenital malformations, but cardiomegaly is present. From the histologic appearance of the bone marrow shown in the figure, which of the following is the most likely cause of these findings?

· Maternal IgG crossing the placenta

· Chromosomal anomaly of the fetus

· Congenital neuroblastoma

· Inheritance of two abnormal CFTR genes

· Infection with parvovirus B19

Answer 37

Infection with parvovirus B19

The erythroid precursors demonstrate large, pink, intranuclear inclusions typical of parvovirus. In adults, such an infection typically causes fifth disease, which is self-limiting. However, this is one of the “O” infections in the TORCH mnemonic describing congenital infections (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex infection). Parvovirus infection in the fetus can lead to a profound fetal anemia with cardiac failure and hydrops fetalis. Erythroblastosis fetalis is unlikely to occur in a first pregnancy, and only erythroid expansion is present, not erythroid inclusions. Although a variety of chromosomal anomalies—monosomy X, in particular—may lead to hydrops, malformations are typical. Congenital tumors are an uncommon cause of hydrops, and they would produce a mass lesion, which was not described in this case. Cystic fibrosis does not affect erythropoiesis.
See pages 459-461.

Question 38

An infant born at term develops abdominal distention in the first week of life. Meconium ileus is diagnosed. The infant has persistent steatorrhea and fails to develop normally. Later in childhood, multiple respiratory tract infections lead to widespread bronchiectasis. Which of the following laboratory findings is most likely related to this child’s underlying disease?

· Decreased serum thyroxine level

· Positive HIV serology

· Elevated sweat chloride level

· Increased urine homovanillic acid level

· Hyperbilirubinemia

Answer 38

Elevated sweat chloride level

The findings are typical of cystic fibrosis, which is an inherited defect in chloride transport. Cretinism from hypothyroidism results in impaired central nervous system and skeletal development. An infant with congenital HIV infection may have a variety of opportunistic infections but not meconium ileus. Increased urine homovanillic acid is a feature of neuroblastoma, a mass lesion that could also cause bowel obstruction but not meconium ileus. Neonatal jaundice has a variety of causes, including the inherited disorder galactosemia.
See pages 465-471.

Question 39

An 80-year-old man with a lengthy history of smoking survived a small myocardial infarction several years ago. He now reports chest and leg pain during exercise. On physical examination, his vital signs include temperature of 36.9°C, pulse 81/min, respirations 15/min, and blood pressure 165/100 mm Hg. Peripheral pulses are poor in the lower extremities. There is a 7-cm pulsating mass in the midline of the lower abdomen. Laboratory studies include two fasting serum glucose measurements of 170 mg/dL and 200 mg/dL. Which of the following vascular lesions is most likely to be present in this patient?

· Aortic dissection

· Arteriovenous fistula

· Atherosclerotic aneurysm

· Glomus tumor

· Polyarteritis nodosa

· Takayasu arteritis

· Thromboangiitis obliterans

Answer 39

Atherosclerotic aneurysm

Abdominal aneurysms are most often related to underlying atherosclerosis. This patient has multiple risk factors for atherosclerosis, including diabetes mellitus, hypertension, and smoking. When the aneurysm reaches this size, there is a significant risk of rupture. An aortic dissection is typically a sudden, life-threatening event with dissection of blood out of the aortic lumen, typically into the chest, without a pulsatile mass. The risk factors of atherosclerosis and hypertension underlie aortic dissection. An arteriovenous fistula can produce an audible bruit on auscultation. Glomus tumors are usually small peripheral masses. Polyarteritis nodosa can produce small microaneurysms in small arteries. Takayasu arteritis typically involves the aortic arch and branches in children. Thromboangiitis obliterans (Buerger disease) is a rare condition with occlusion of the muscular arteries of the lower extremities in smokers. See pages 507-508.