What is the most common site of origin of thrombotic pulmonary emboli?
A.Deep leg veins
B.Lumen of left ventricle
C.Lumen of right ventricle
E.Superficial leg veins
A young child who presents with megaloblastic anemia is found to have increased orotate in the urine due to a deficiency of orotate phosphoribosyl transferase. This enzyme deficiency decreases the synthesis of which of the following
A 6-year-old female is being evaluated for recurrent episodes of lightheadedness and sweating due to hypoglycemia. These symptoms are not improved by subcutaneous injection of epinephrine. Physical examination reveals an enlarged liver and a single subcutaneous xanthoma. An abdominal CT scan reveals enlargement of the liver along with bilateral enlargement of the kidneys. Laboratory examination reveals increased serum uric acid and cholesterol with decreased serum glucose levels. Following oral administration of fructose, there is no increase in blood glucose levels. A liver biopsy specimen reveals increased amounts of glycogen in hepatocytes, which also have decreased levels of glucose-6-phosphatase. Which of the following is the most likely diagnosis?
A.Andersen’s syndrome (type IV glycogen storage disease)
B.Cori’s disease (type III glycogen storage disease)
C.McArdle’s syndrome (type V glycogen storage disease)
D.Pompe’s disease (type II glycogen storage disease)
E.von Gierke’s disease (type I glycogen storage disease)
A 2-month-old girl presents with a soft, high-pitched, mewing cry and is found to have microcephaly, low-set ears and hypertelorism, and several congenital heart defects. Which of the following chromosomal abnormalities is most likely to produce these symptoms?
A 6-year-old female with a fair complexion is being evaluated for severe mental retardation and seizures. She is found to have a stiff, ataxic gait characterized by jerky movements. She also displays laughter at inappropriate times. Which of the following is the most likely diagnosis?
Which one of the following sequences correctly describes the usual temporal sequence of T-lymphocyte maturation within the cortex and medulla of the thymus?
A.Double negative double positive single positive
B.Double negative single positive double positive
C.Double positive double negative single positive
D.Double positive single positive double negative
E.Single positive double positive double negative
After receiving incompatible blood, a patient develops a transfusion reaction in the form of back pain, fever, shortness of breath, and hematuria. How is this type of immunologic reaction classified?
A.Systemic anaphylactic reaction
B.Systemic immune complex reaction
C.Delayed type hypersensitivity reaction
D.Complement-mediated cytotoxicity reaction
E.T cell–mediated cytotoxicity reaction
A 28-year-old woman’s first son dies at 7 months of age due to severe combined immunodeficiency disease (SCID). Subsequent workup reveals a mutation in the gene for the common chain of the interleukin 2 receptor (IL2RG). Lymphocyte and red cell adenosine deaminase (ADA) levels are within normal limits. Workup during the woman’s second pregnancy reveals that the fetus has the same abnormality found in her first son. Bone marrow is obtained from the 29-year-old father and is enriched with CD34+ cells (hematopoietic cell progenitors). It is then injected intraperitoneally by percutaneous, ultrasound-guided injection at 16, 17.5, and 18.5 weeks of gestation. At 11 months of life, the second child is found to be clinically normal. Which of the following is the mode of inheritance of this patient’s disease?
A 4-year-old African boy develops a rapidly enlarging mass that involves the right side of his face. Biopsies of this lesion reveal a prominent “starry sky” pattern produced by proliferating small, noncleaved malignant lymphocytes. Based on this microscopic appearance, the diagnosis of Burkitt’s lymphoma is made. This neoplasm is associated with chromosomal translocations that involve which of the following?
Gastric carcinoma is most common in which one of the listed geographic locations?
A 23-year-old female presents with the recent onset of vaginal discharge. Physical examination reveals multiple clear vesicles on her vulva and vagina. A smear of material obtained from one of these vesicles reveals several multinucleated giant cells with intranuclear inclusions and ground-glass nuclei. These vesicles are most likely the result of an infection with which of the following
B.Herpes simplex virus (HSV)
C.Human papillomavirus (HPV)
A 33-year-old male in an underdeveloped country presents with a markedly edematous right foot that has multiple draining sinuses. A Gram stain from one of these draining sinuses reveals gram-positive filamentous bacteria that are partially acid-fast. Which of the following organisms is the most likely cause of this abnormality?
A 35-year-old female who lives in the southeastern portion of the United States and likes to hike in the Great Smoky Mountains presents with a spotted rash that started on her extremities and spread to her trunk and face. A biopsy of one of these lesions reveals necrosis and reactive hyperplasia of blood vessels. Which of the following is the most likely causative agent of her disease
An apathetic male infant in an underdeveloped country is found to have peripheral edema, a “moon” face, and an enlarged, fatty liver. Which one of the following mechanisms is involved in the pathogenesis of this child’s abnormalities?
A.Decreased protein intake leads to decreased lipoproteins
B.Decreased caloric intake leads to hypoalbuminemia
C.Decreased carbohydrate intake leads to hypoglycemia
D.Decreased fluid intake leads to hypernatremia
E.Decreased fat absorption leads to hypovitaminosis
A patient with malabsorption who develops a deficiency of vitamin A is most likely to subsequently develop which of the following?
Which one of the following individuals is most likely to have a deficiency of vitamin E?
A.A premature male infant with skeletal muscle weakness and a hemolytic anemia
B.A 36-year-old male with progressive night blindness
C.A 45-year-old female with bleeding and a prolonged PT and PTT
D.A 48-year-old female with chronic atrophic gastritis and anemia
E.A 67-year-old female with osteopenia and bone pain
A 62-year-old male alcoholic is brought into the emergency room acting very confused. Physical examination reveals a thin and emaciated male who has problems with memory, ataxia, and paralysis of his extraocular muscles. Extensive workup reveals atrophy and small hemorrhages in the periventricular region of his brain and around the mamillary bodies. These signs and symptoms are most consistent with which of the following deficiencies
Laboratory examination of a 46-year-old male who presents with decreasing vision and photophobia finds a high anion–gap metabolic acidosis. These findings are most consistent with this individual having ingested which of the following substances?
A newborn female infant develops edema, jaundice, and trouble breathing. The blood type of the mother is AB negative, while the baby and the father are both B positive. The mother’s only other pregnancy was unremarkable, and she has never received any blood or blood products. Laboratory examination reveals a positive Coombs (DAT) test. Which of the following is the most likely diagnosis
A.ABO hemolytic disease of the newborn
B.Hemoglobin H disease
C.Hyaline membrane disease of the newborn
E.Rh hemolytic disease of the newborn
Which one of the listed clinical scenarios is most consistent with a diagnosis of SIDS?
A.A 2-year-old female dies suddenly and no autopsy is performed
B.A 3-month-old female dies during sleep and the cause of death is unknown after autopsy
C.A 4-week-old female dies from respiratory complications after being born 10 weeks prematurely
D.A 9-month-old male dies and an autopsy finds evidence of repeated bone fractures and bilateral retinal hemorrhages
E.A male is stillborn at 29 weeks of gestation to a mother with obstetrical complications
Answers & Explanation
1-The answer is: A
An embolus is a detached intravascular mass that has been carried by the blood to a site other than where it was formed. Emboli basically can be thrombotic or embolic, but most originate from thrombi. These thromboemboli, most of which originate in the deep veins of the lower extremities, may embolize to the lungs. The majority of small pulmonary emboli do no harm, but, if they are large enough, they may occlude the bifurcation of the pulmonary arteries (saddle embolus), causing sudden death. Arterial emboli most commonly originate within the heart on abnormal valves (vegetations) or mural thrombi following myocardial infarctions. If there is a patent foramen ovale, a venous embolus may cross over through the heart to the arterial circulation, producing an arterial (paradoxical) embolus.
Types of nonthrombotic emboli include fat emboli, air emboli, and amniotic fluid emboli. Fat emboli, which result from severe trauma and fractures of long bones, can be fatal as they can damage the endothelial cells and pneumocytes within the lungs. Air emboli are seen in decompression sickness, called caisson disease or the bends, while amniotic fluid emboli are related to the rupture of uterine venous sinuses as a complication of childbirth. Amniotic fluid emboli can also lead to a fatal disease, disseminated intravascular coagulopathy (DIC), which is marked by the combination of intravascular coagulation and hemorrhages. In this setting DIC results from the high thromboplastin activity of amniotic fluid.
2.The answer is: C
The synthesis of pyrimidines begins with the conversion of glutamine to carbamoyl phosphate. This step, which is the committed step in pyrimidine synthesis, is catalyzed by the enzyme carbamoyl phosphate synthetase II (CPSII) and requires 2ATP and CO2. After several biochemical steps orotate is formed; orotate is then converted to orotidine 5'-monophosphate (OMP) by the enzyme orotate phosphoribosyl transferase. Subsequently OMP is converted to uridine 5'-monophosphate (UMP) by the enzyme OMP decarboxylase. A deficiency of either of these two enzymes leads to a disorder called orotic aciduria, which is characterized by orotate in the urine, abnormal growth, and megaloblastic anemia. Next UMP is converted to CTP, while dUMP is converted by thymidylate synthase to dTMP. This latter step also involves folate and is inhibited by the folate analogue methotrexate, while thymidylate synthase is inhibited by the thymine analogue 5-flurouracil (5-FU). Finally, the ribonucleoside diphosphates (ADP, GDP, CDP, and UDP) are converted to deoxyribonucleoside diphosphates by ribonucleotide reductase, an enzyme that is inhibited by increased levels of dATP, as seen in individuals with the autosomal recessive (Swiss type) form of SCID, which is due to a deficiency of adenosine deaminase (ADA).
3.The answer is: E
The glycogen storage diseases are due to defective metabolism of glycogen, and at least 11 syndromes stemming from genetic defects in the responsible enzymes have been described. Most of these glycogenoses are inherited as autosomal recessive disorders. von Gierke’s disease (type I) results from deficiency of glucose-6-phosphatase, the hepatic enzyme needed for conversion of G6P to glucose, with glycogen accumulation particularly in the enlarged liver and kidney and hypoglycemia. Diagnosis requires biopsy demonstration of excess liver glycogen plus either absent or low liver glucose-6-phosphatase activity, or a diabetic glucose tolerance curve, or hyperuricemia. von Gierke’s disease is the major hepatic or hepatorenal type of glycogenosis. Lysosomal glucosidase deficiency causes Pompe’s disease (type II). Glycogen storage is widespread but most prominent in the heart (cardiomegaly). In brancher glycogenosis (type IV) there is accumulation of amylopectin or abnormal glycogen in the liver, heart, skeletal muscle, and brain. The major myopathic form, McArdle’s disease (type V), is due to lack of muscle phosphorylase.
4.The answer is: B
Several genetic diseases are characterized by a deletion of part of an autosomal chromosome. The 5p– syndrome is also called the cri-du-chat syndrome, as affected infants characteristically have a high-pitched cry similar to that of a kitten. Additional findings in this disorder include severe mental retardation, microcephaly, and congenital heart disease. 4p–, also called Wolf-Hirschhorn syndrome, is characterized by pre- and postnatal growth retardation and severe hypotonia. Affected infants have many defects including micrognathia and a prominent forehead. The 11p– syndrome is characterized by the congenital absence of the iris (aniridia) and is often accompanied by Wilms tumor of the kidney. The 13q– syndrome is associated with the loss of the Rb suppressor gene and the development of retinoblastoma. Deletions involving chromosome 15 (15q–) may result in either Prader-Willi syndrome or Angelman’s syndrome depending on whether the defect involves the paternal or the maternal chromosome (genetic imprinting). 17p–, also known as Smith-Margens syndrome, is associated with self-destructive behavior.
5.The answer is: C
Genetic imprinting refers to the fact that different diseases may result from the same chromosomal deletion depending on whether that deletion specifically involves either the maternal chromosome or the paternal chromosome. This finding is in sharp contrast to the classic concept of Mendelian inheritance, which states that the phenotype of a certain allele is independent of whether the chromosome is the maternal or the paternal chromosome. The best example of genetic imprinting involves deletions involving chromosome 15 (15q–). If the deletion involves the maternal chromosome, then Angelman’s syndrome results, while deletions involving the paternal chromosome result in Prader-Willi syndrome. Angelman’s syndrome is characterized by severe mental retardation, seizures, a stiff ataxic gait with jerky movements, inappropriate laughter, and occasional oculocutaneous albinism. Because of the combination of ataxic gait and inappropriate laughter, these patients are sometimes referred to as “happy puppets.” Prader-Willi syndrome is characterized by short stature, obesity, mild to moderate mental retardation, small hands and feet, and hypogonadism, which is characterized in males by cryptorchidism and micropenis and in females by hypoplastic labia.
The cause of genetic imprinting is not known, but it may relate to the degree of methylation of genes. Genes that are more highly methylated are less likely to be transcribed into messenger RNA. Note that a loss of chromosome 15 can also occur if two parental chromosomes of the same type are derived from the same parent. This condition is called uniparental disomy, whereas the normal condition is called biparental disomy. Inheritance of the same (duplicated) chromosome is called isodisomy, while inheritance of homologues from the same parent is called heterodisomy. To illustrate this concept, consider paternal uniparental disomy of chromosome 15. This refers to inheriting two copies of paternal chromosome 15 and no maternal chromosome 15. Therefore, this is essentially the same as a deletion of maternal chromosome 15, which produces Angelman’s syndrome.
Inheriting two copies of paternal chromosome 11 results in Beckwith-Wiedemann syndrome. This is not a trisomy, as the maternal chromosome is lost, and therefore this would be a paternal uniparental disomy for chromosome 11. This syndrome is characterized by exomphalos, macroglossia, and gigantism (EMG). Patients also develop hypoglycemia because the genes for insulin and insulinlike growth factors are located in this region. Smith-Margens syndrome (17p–) is associated with self-destructive behavior, while Wolf-Hirschhorn syndrome (4p–) is characterized by growth retardation, severe hypotonia, and micrognathia.
6.The answer is: A
T cells arise from precursor cells in the bone marrow that migrate to the thymus and mature. Like B cells, T cells originate from a common lymphoid stem cell that includes intranuclear terminal deoxynucleotidyl transferase (TdT) and surface antigens CD34 and CD38. This stage of development occurs prior to the migration of the developing cell to the thymus and is called the prethymus stage. There are three stages of maturation within the thymus. Stage I occurs in the outer cortex of the thymus, where the developing T lymphocytes (thymocytes) obtain the surface antigen CD7 followed by CD2 and CD5. These stage I (or early) thymocytes lack both CD4 or CD8 and are called double-negative cells. These cells make up about 10% of the thymocytes in the thymus. The next step in development, which starts in the cortex and continues into the medulla, involves generation of an intact T cell receptor (TCR) on the cell surface. The TCR is a heterodimer, usually made up of an and a chain, each having a variable (antigen-binding) region and a constant region, analogous to the immunoglobulin molecule. Early in the formation of TCR, called stage II, the intermediate (common) thymocytes acquire both CD4 and CD8 molecules and are called double-positive T cells. They are the majority of thymocytes in the thymus (80%). Stage III occurs in the medulla, where the T cells lose either the CD4 or the CD8 antigen. These mature thymocytes, which are single-positive cells, make up about 15% of the thymus thymocytes. Post-thymus T cells are either CD4+ or CD8+. CD4+ cells function as helper cells, while CD8+ cells function as cytotoxic cells. In normal, healthy individuals, the helper/suppressor ratio (e.g., CD4/CD8 ratio) in the peripheral blood is about 2:1. That is, about 40% of peripheral lymphocytes are helper cells and 20% of peripheral lymphocytes are cytotoxic T cells.
7.The answer is: D
A blood transfusion reaction is a type II hypersensitivity reaction that is mediated by antibodies reacting against antigens present on the surface of blood group antigens or irregular antigens present on the donor’s red blood cells. Type II hypersensitivity reactions result from attachment of antibodies to changed cell surface antigens or to normal cell surface antigens. Complement-mediated cytotoxicity occurs when IgM or IgG binds to a cell surface antigen with complement activation and consequent cell membrane damage or lysis. Blood transfusion reactions and autoimmune hemolytic anemia are examples of this form. Systemic anaphylaxis is a type I hypersensitivity reaction in which mast cells or basophils that are bound to IgE antibodies are reexposed to an allergen, which leads to a release of vasoactive amines that causes edema and broncho- and vasoconstriction. Sudden death can occur. Systemic immune complex reactions are found in type III reactions and are due to circulating antibodies that form complexes upon reexposure to an antigen (such as foreign serum), which then activates complement. This process is followed by chemotaxis and aggregation of neutrophils, which leads to release of lysosomal enzymes and eventual necrosis of tissue and cells. Serum sickness and Arthus reactions are examples of type III reactions. Delayed type hypersensitivity is type IV and is due to previously sensitized T lymphocytes, which release lymphokines upon reexposure to the antigen. This takes time—perhaps up to several days following exposure. The tuberculin reaction is the best-known example. T cell–mediated cytotoxicity leads to lysis of cells by cytotoxic T cells in response to tumor cells, allogenic tissue, and virus-infected cells. These cells have CD8 antigens on their surfaces.
8.The answer is: E
Patients with severe combined immunodeficiency disease (SCID) have defects of lymphoid stem cells involving both T cells and B cells. These patients have severe abnormalities of immunologic function with lymphopenia. They are at risk for infection with all types of infectious agents, including bacteria, mycobacteria, fungi, viruses, and parasites. Patients have a skin rash at birth, possibly due to a graft-versus-host reaction from maternal lymphocytes. Patients are particularly prone to chronic diarrhea, due to rotavirus and bacteria, and to oral candidiasis. About 50% of patients with the autosomal recessive form (Swiss type) lack the enzyme adenosine deaminase (ADA) in their red cells and leukocytes. This leads to accumulation of adenosine triphosphate and deoxyadenosine triphosphate, both of which are toxic to lymphocytes. The other form of SCID is an X-linked form due to a defect in the IL-2 receptor.
9.The answer is: C
There are several mechanisms through which proto-oncogenes (p-oncs) can become oncogenic (c-oncs). Normal cellular genes (proto-oncogenes) may become oncogenic by being incorporated into the viral genome (forming v-oncs), or they may be activated by other processes to form cellular oncogenes (c-oncs). These other processes include gene mutations, chromosomal translocations, and gene amplifications. Gene mutations, such as point mutations, are associated with the formation of cancers by mutant c-ras oncogenes. Chromosomal translocations are associated with the development of many types of cancers, one example of which is Burkitt’s lymphoma. The most common translocation associated with Burkitt’s lymphoma is t(8;14), in which the c-myc oncogene on chromosome 8 is brought in contact with the immuno-globulin heavy chain gene on chromosome 14. Two other examples of chromosomal translocations are the association of chronic myelocytic leukemia (CML) with t(9;22), which is the Philadelphia chromosome, and the association of follicular lymphoma with the translocation t(18;14). The former involves the proto-oncogene c-abl, which is rearranged in proximity to a break point cluster region (bcr) on chromosome 22. The resultant chimeric c-abl/bcr gene encodes a protein with tyrosine kinase activity. The t(18;14) translocation involves the bcl-2 oncogene on chromosome 18. Expression of the oncogene bcl-2 is associated with the prevention of apoptosis in germinal centers. Examples of associations that involve gene amplification include N-myc and neuroblastoma, c-neu and breast cancer, and erb-B and breast and ovarian cancer. Gene amplifications can be demonstrated by finding doublet minutes or homogenous staining regions.
10.The answer is: C
There are marked differences in the incidence of various types of cancer in different parts of the world. The highest rates for gastric carcinoma are found in Japan, Chile, China, and Russia, while it is much less common in the United States, the United Kingdom, Canada, and France. The high rates for gastric cancer in Japan might be related to dietary factors, such as eating smoked and salted foods. Other examples of geographic variations in the incidence of neoplasms include nasopharyngeal carcinoma, liver cancer, and trophoblastic disease. Nasopharyngeal carcinoma, associated with the Epstein-Barr virus, is rare in most parts of the world, except for parts of the Far East, especially China. Liver cancer is associated with both hepatitis B infection and high levels of aflatoxin B1. It is endemic in large parts of Africa and Asia. Trophoblastic diseases, including choriocarcinoma, have high rates of occurrence in the Pacific rim areas of Asia. In contrast, Asian populations have a very low incidence of prostate cancer.
11.The answer is: B
The cytopathic effect of viruses is often a clue to the diagnosis of the type of infection that is present. There are several types of herpesviruses, which are relatively large, double-stranded DNA viruses. Infection by herpes simplex virus (HSV) or varicella-zoster virus (VZV) is recognized by nuclear homogenization (ground-glass nuclei), intranuclear inclusions (Cowdry type A bodies), and the formation of multinucleated cells. Herpes simplex type 2, a sexually transmitted viral disease, results in the formation of vesicles that ulcerate and cause burning, itching, and pain. These lesions heal spontaneously, but the virus remains dormant in the lumbar and sacral ganglia. Recurrent infections may occur, and transmission to the newborn during delivery is a feared complication that may be fatal to the infant. Shingles and chickenpox are caused by herpes zoster, which is identical to varicella. Cytomegalovirus (CMV) causes both the nucleus and the cytoplasm of infected cells to become enlarged. Infected cells have large, purple intranuclear inclusions surrounded by a clear halo and smaller, less prominent basophilic intracytoplasmic inclusions. Adenoviruses can produce similar inclusions, but the infected cells are not enlarged. Adenoviruses also produce characteristic smudge cells in infected respiratory epithelial cells. Human papillomavirus (HPV) infection may produce a characteristic effect that is called koilocytosis. Histologic examination reveals enlarged squamous epithelial cells that have shrunken nuclei (“raisinoid”) within large cytoplasmic vacuoles. Candidiasis is the most common fungal infection of the vagina and is especially common in patients who have diabetes or take oral contraceptives. Candida infection causes vulvar itching and produces a white discharge. Microscopic examination of the vaginal discharge reveals yeast and pseudohyphae. T. vaginalis, a large, pear-shaped, flagellated protozoan, causes severe vaginal itching with dysuria. It produces a thick yellow-gray discharge.
12.The answer is: D
Nocardia (N. asteroides) and Actinomyces species are classified as filamentous soil bacteria, although they are often described among the fungi. A. israelii is a normal inhabitant of the mouth; it can be seen in the crypts of tonsillectomy specimens. Actinomyces is a branched, filamentous gram-positive bacteria. Two forms of disease produced by Actinomyces are cervicofacial actinomyces and pelvic actinomyces. The former consists of an indurated (lumpy) jaw with multiple draining fistulas or abscesses. Small yellow colonies called sulfur granules may be seen in the draining material. Histologic section reveals tangled masses of gram-positive filamentous bacteria. Cultures of Actinomyces grow as white masses with a domed surface, which is called a “molar tooth” appearance. Another filamentous gram-positive bacteria is N. asteroides. A characteristic that helps to differentiate these two is the fact that Nocardia is partially acid-fast. “Partial” means using weak mineral acids in the acid-fast stain. Nocardiae are aerobic and acid-fast, in contrast to Actinomyces species, which are strict anaerobes and not acid-fast. Inhaled nocardial bacteria produce lung or skin infections. Progressive pneumonia with purulent sputum and abscesses is suggestive of nocardiosis, especially if dissemination to the brain or subcutaneous tissue occurs. Nocardia is also one cause of mycetoma, a form of chronic inflammation of the skin that causes indurated abscesses with multiple draining sinuses. Patients who develop nocardiosis are often immunosuppressed, and transplant rejection, steroid therapy, AIDS, or alveolar proteinosis are often antecedent. Organisms in sputum, pus, or bronchial lavage specimens are gram-positive. A modified acid-fast stain should be used for diagnosis.
C. diphtheriae is a small, pleomorphic gram-positive bacillus that may have club-shaped swellings at either pole. These rods tend to arrange themselves at right angles, producing characteristic V or Y configurations described as “Chinese characters.” C. diphtheriae produces a toxin that blocks protein synthesis by causing irreversible inactivation of elongation factor 2 (EF-2). This toxin can produce a pseudomembrane covering the larynx, which is difficult to peel away without causing bleeding, and heart damage with fatty change. L. monocytogenes is a short, gram-positive, non-spore-forming bacillus that can produce neonatal disease or can result in stillbirth. Characteristics that are unique to Listeria include a tumbling motility on hanging drop and an umbrella-shaped motility pattern when a specimen is stabbed into a test tube agar slant.
13.The answer is: E
Rickettsia are obligate intracellular parasites that infect endothelial cells and produce symptoms as a result of vasculitis and formation of microthrombi. Serologic tests for rickettsia include complement fixation tests and the Weil-Felix agglutination reaction. The basis for the latter test is the fact that the sera of infected patients can agglutinate strains of Proteus vulgaris. There are numerous types of rickettsia that produce many different diseases. Examples include Rocky Mountain spotted fever (RMSF, caused by R. rickettsii), epidemic typhus (caused by R. prowazekii and spread by the human body louse Pediculus humanus), endemic typhus (caused by R. typhi and spread by lice), scrub typhus (caused by R. tsutsugamushi and spread by mites), ehrlichiosis, and Q fever (caused by C. burnetii and spread not by vectors but by inhalation of aerosols). RMSF is found not only in the Rocky Mountains, but also the southeastern and south central United States. The vector in the Rocky Mountains is the wood tick (Dermacentor andersoni), while in the southeast it is the dog tick (Dermacentor variabilis) and in the south central United States it is the Lone Star tick. The animal reservoirs for RMSF are wild rodents and dogs. The rash of RMSF characteristically begins peripherally and spreads centrally to the trunk and face. The pathology involves infection of blood vessels producing thrombosis. Intracellular bacilli form parallel rows in an end-to-end arrangement (“flotilla at anchor facing the wind”). Patients also develop muscle pain and high fever.
Bartonella infections are also characterized by proliferations of blood vessels. Examples of Bartonella include B. quintana, B. henselae, and B. bacilliformis, the causative agent of Oroya fever. B. quintana is spread by the human body louse and is the causative agent of trench fever (seen in the trenches of World War I) and bacillary angiomatosis. This latter term refers to a lesion seen in patients with AIDS consisting of a lobular proliferation of capillaries with abundant leukocytoclastic debris. B. henselae is the causative agent of cat-scratch fever. Histologically, this disease is characterized by the formation of stellate microabscesses with necrotizing granulomas.
14.The answer is: A
Protein-energy malnutrition (PEM) in underdeveloped countries leads to a spectrum of symptoms from kwashiorkor at one end to marasmus at the other. Marasmus, caused by a lack of caloric intake (i.e., starvation), leads to generalized wasting, stunted growth, atrophy of muscles, and loss of subcutaneous fat. There is no edema or hepatic enlargement. These children are alert, not apathetic, and are ravenous. In contrast, children with kwashiorkor, which is characterized by a lack of protein despite adequate caloric intake, have peripheral edema, a “moon” face, and an enlarged, fatty liver. The peripheral edema is caused by decreased albumin and sodium retention, while the fatty liver is caused by decreased synthesis of the lipoproteins necessary for the normal mobilization of lipids from liver cells. Additionally, these children have “flaky paint” areas of skin and abnormal pigmented streaks in their hair (“flag sign”). In children with marasmus, the skin is inelastic due to loss of subcutaneous fat. In either severe kwashiorkor or marasmus, thymic atrophy may result in the reduction in number and function of circulating T cells. B cell function (i.e., immunoglobulin production) is also depressed, so that these children are highly vulnerable to infections.
15.The answer is: D
The symptoms of vitamin A deficiency result from abnormalities involving the normal functions of vitamin A. These normal functions include maintaining mucus-secreting epithelium, restoring levels of the visual pigment rhodopsin, increasing immunity to infections, and acting as an antioxidant. Deficiencies of vitamin A result in squamous metaplasia of mucus membranes, not intestinal metaplasia. Squamous metaplasia of the respiratory tract leads to increased numbers of pulmonary infections due to lack of the normal protective mucociliary “elevator.” Squamous metaplasia of the urinary tract leads to increased numbers of urinary tract stones, while such metaplasia in sebaceous and sweat glands of dry skin causes follicular hyperkeratosis and predisposes to acne. There are numerous eye changes produced by a vitamin A deficiency. These changes include dry eyes (xerophthalmia), soft cornea (keratomalacia), and elevated white plaques of keratin debris on the conjunctiva (Bitot’s spots). Because vitamin A is important in the normal function of rhodopsin, a visual pigment important for vision in dim light, a deficiency of vitamin A is associated with poor vision in dim light. This night blindness is usually the first symptom seen in patients with a vitamin A deficiency. Rather than causing acute leukemia, vitamin A is used with good results in the treatment of acute promyelocytic leukemia. Megaloblastic anemia is associated with a deficiency of either vitamin B12 or folate, while a deficiency of vitamin D leads to decreased mineralization of bones (soft bones).
16.The answer is: A
Vitamin E ( tocopherol, the most potent form, and tocotrienols) functions primarily as an antioxidant. As such, it protects membranes, especially the membranes of erythrocytes, from peroxidation of polyunsaturated fatty acids. This antioxidation property of vitamin E acts in concert with selenium. Deficiencies of vitamin E may produce spinocerebellar degeneration and skeletal muscle abnormalities. Manifestations of the neuropathologic changes, which affect the posterior columns of the spinal cord, include decreased tendon reflexes, ataxia, and loss of pain, position, and vibration sense. Note that red cells use vitamin E to protect their membranes from oxidation, and a deficiency of vitamin E in newborns can lead to a hemolytic anemia. In contrast, progressive night blindness is associated with a deficiency of vitamin A; bleeding with a prolonged PT and PTT is associated with a deficiency of vitamin K; chronic atrophic gastritis and anemia are associated with a deficiency of vitamin B12; and osteopenia and bone pain are associated with a deficiency of vitamin D.
17.The answer is: E
Vitamin B1 (thiamine) has three important functions. It participates in oxidative decarboxylation of a-keto acids; participates as a cofactor for transketolase in the pentose phosphate path; and participates in maintaining neural membranes. The causes of thiamine deficiency include poor diet, deficient absorption and storage, and accelerated destruction of thiamine diphosphate. This deficiency may be seen in alcoholics and prisoners of war because of poor nutrition, or it may be seen in individuals who eat large amounts of polished rice. (Polishing rice removes the outer, thiamine-containing portion of the grain.) Thiamine deficiency (called beriberi) mainly affects two organ systems, the heart and the nervous system. If the heart is affected in a patient with beriberi, it may become dilated and flabby. Patients may also develop peripheral vasodilation that leads to a high-output cardiac failure and marked peripheral edema. This combination of vascular abnormalities is called wet beriberi. The peripheral nerves in beriberi may be damaged by focal areas of myelin degeneration, which leads to footdrop, wristdrop, and sensory changes (numbness and tingling) in the feet and lower legs. These symptoms are referred to as dry beriberi. Thiamine deficiency may produce the central nervous system (CNS) symptoms of Wernicke-Korsakoff syndrome. Wernicke’s encephalopathy consists mainly of foci of hemorrhages and necrosis in the mammillary bodies and about the ventricular regions of the thalamus and hypothalamus, about the aqueduct in the midbrain, and in the floor of the fourth ventricle. Symptoms of Wernicke’s syndrome include progressive dementia (confusion), ataxia, and paralysis of the extraocular muscles—often with bilateral lateral rectus, or sixth nerve, palsies (ophthalmoplegia). Korsakoff psychosis is a thought disorder that produces retrograde memory failure and confabulation.
18.The answer is: E
Many environmental chemicals are potential causes of quite serious human diseases. Methanol, originally called wood alcohol, is metabolized in the body by the enzyme alcohol dehydrogenase to formaldehyde and formic acid. These metabolites cause necrosis of retinal ganglion cells, which leads to a metabolic acidosis and blindness. It is interesting to note that the treatment for acute methanol ingestion is IV ethyl alcohol, because it is also metabolized by alcohol dehydrogenase and therefore ties up this enzyme. Cadmium, which can be found in tobacco smoke, has been implicated in producing not only an acute form of pneumonia, but, with chronic exposure to small concentrations of cadmium vapors, diffuse interstitial pulmonary fibrosis and an increased incidence of emphysema as well. Nickel can cause contact dermatitis, which is a type IV hypersensitivity reaction, while mercury toxicity damages the kidneys and the brain. The neurologic symptoms include a tremor due to cerebellar abnormalities, and mental changes. Historically the use of mercury in the hatmaking industry caused these symptoms and resulted in the expression “mad as a hatter.” A famous widespread outbreak of mercury poisoning occurred in the Minamata coastal region of Japan (and led to the term Minamata disease). Cobalt poisoning can produce a dilated cardiomyopathy.
19.The answer is: E
Hemolytic disease of the newborn (HDN) is a type of isoimmune hemolytic anemia that is caused by maternal antibodies that react against fetal red blood cells. Once the maternal antibodies cross the placenta, the fetal red cells are destroyed, leading to a hemolytic anemia. The breakdown of hemoglobin leads to hyperbilirubinemia (jaundice), which is due to severe unconjugated hyperbilirubinemia, as the released heme is not easily conjugated by the immature newborn liver, which is deficient in glucuronyl transferase. The unconjugated bilirubin is water-insoluble and has an affinity for lipids. In an infant with a poorly developed blood-brain barrier, the bilirubin may bind to the lipids in the brain and produce kernicterus. The severe anemia may result in congestive heart failure, which, together with hypoproteinemia may lead to generalized edema (anasarca), which in its most severe form is called hydrops fetalis. In the peripheral blood of the newborn, many immature red blood cells may be found (nucleated RBCs or normoblasts). This condition is called erythroblastosis and led to another name for HDN being erythroblastosis fetalis.
In order for the mother to make antibodies that are directed against fetal erythrocyte antigens, she must lack the erythrocyte antigens that the child has, which were inherited from the father. The most important erythrocyte antigens involved in HDN are the Rh and the ABO antigens. The most important Rh antigen is the D antigen. Therefore, for Rh incompatibility, the mother must be Rh negative (d), the child Rh positive (D). For ABO incompatibility, the mother must be type O (lacking the A and B antigens), the child type A or B. ABO incompatibility is the most common cause of hemolytic disease of the newborn. Usually the disease is less severe than HDN due to Rh incompatibility because there is poor expression of blood group antigens A and B on neonatal red cells.
20.The answer is: B
Sudden infant death syndrome (SIDS) is a heterogeneous, multifactorial disorder, but by definition it refers to sudden death of infant under 1 year of age that is unexplained after thorough examination. Most cases of SIDS occur between 2 and 4 months of life, and the child usually dies during sleep (“crib death” or “cot death”). A risk factor for SIDS is sleeping in a prone position. Therefore healthy infants should sleep on their back or side. Maternal factors associated with SIDS include age less than 20, being unmarried, low socioeconomic group, smoking, and drug abuse. Infant factors associated with SIDS include prematurity, low birth weight, male sex, and a history of SIDS in a sibling. In contrast to SIDS, death from respiratory complications after being born 10 weeks prematurely is suggestive of hyaline membrane disease, while evidence of repeated bone fractures and bilateral retinal hemorrhages is suggestive of trauma, child abuse, or “shaken baby” syndrome.