Robbins and Cotran Review of Pathology ( PDFDrive ) (1)

1 3 8 U N I T I   General Pathology

t­ransforming growth factor beta (TGF-β) signaling pathway that this is an isolated anomaly, and not part of a syndrome
and affect the expression of homeobox (HOX) genes. These or disease with a defined genetic cause. Most congenital mal-
genes are important in embryonal patterning of limbs, verte- formations, including cleft lip, are not determined by a single
brae, and craniofacial structures. Embryonic rhombomeres gene and may be conditioned by environmental influences.
can be affected in their development. The other listed options Multiple genetic susceptibilities, modified by environmental
do not apply to retinoic acid. influences, can underlie the appearance of 20% to 25% of all
birth defects. Of the remaining options, all are more likely to
PBD9 454, 456  BP9 247  PBD8 453  BP8 255–256 produce multiple defects and to reduce fetal growth. Most
chromosomal anomalies are not compatible with survival;
5   A  The findings are typical for fetal growth restriction in the few fetuses (e.g., with sex chromosome aneuploidies
later term, owing to relative sparing of the fetal brain. The and autosomal triploidies such as 13, 18, and 21) that do sur-
findings suggest uteroplacental insufficiency from an in- vive to term and beyond manifest multiple anomalies. Early
trinsic placental abnormality. One cause is a cytogenetic ab- amnion disruption may result in clefts, but more severe de-
normality in the developing embryo that occurs just in the fects are present (e.g., gastroschisis and missing digits or
trophoblast, and only placenta is affected. Congenital syphi- limbs), and stillbirth is the usual consequence. Maternal mal-
lis occurs in the third trimester, when spirochetes can cross nutrition typically results in an infant who is small for ges-
the placenta; there is typically placental and fetal hydrops. tational age. Single gene defects account for less than 10% of
Inborn errors of metabolism such as galactosemia usually anomalies noted at birth. Teratogens account for no more than
manifest after birth because maternal metabolism clears 1% of congenital anomalies. Albucasis (963-1013 ce) is the “fa-
any intermediate products of fetal enzyme deficiencies. Pre- ther of surgery” whose notable work, Al-Tasrif, was composed
eclampsia is marked by maternal hypertension. An Rh in- of 30 volumes on medical science, including 3 volumes on
compatibility leads to fetal and placental hydrops. Trisomy surgery in which he described many surgical procedures. He
21 is more frequent with advancing maternal age, but in this designed dozens of surgical instruments (including the bulb
case no fetal anomalies were noted. syringe we have all used) and was the first to use silk sutures.

PBD9 456–457  BP9 247  PBD8 455  BP8 256–257 PBD9 453, 455  BP9 248  PBD8 450–452  BP8 240–241

6   B  This is developmental dysplasia of the hip. Most con-  9 B Alcohol is one of the most common environmen-
genital malformations, particularly malformations that are tal teratogens affecting fetuses, although the effects can be
isolated defects, have no readily identifiable cause. Most de- subtle. There is no threshold amount of alcohol consump-
fects are believed to be caused by the inheritance of a certain tion by the mother to produce fetal alcohol syndrome; no
number of genes and by the interaction of those genes with amount is safe. Children with fetal alcohol syndrome tend
environmental factors. Their transmission follows the rules to be developmentally impaired throughout childhood, but
for multifactorial inheritance. The recurrence rate is believed the physical anomalies tend to become less apparent as the
to be 2% to 7% and is the same for all first-degree relatives, child matures. Vertebral abnormalities, including scolio-
regardless of sex and relationship to the index case. Some sis, can be present. The liver can have fatty metamorphosis
populations may have more carriers of these genes. with hepatomegaly and elevated serum transaminases. The
major effects of congenital rubella occur during organogen-
PBD9 454–455  BP9 247  PBD8 448–450  BP8 240–241 esis in the first trimester and result in more pronounced de-
fects, including congenital heart disease. Maternal diabetes
7   A  Rubella infection in the first trimester, when organo- often results in a larger infant, and malformations may be
genesis is occurring (3 to 9 weeks’ gestation), can lead to present. Placenta previa, a low-lying placenta at or near the
embryopathy with cardiac, ocular, skin, central nervous sys- cervical os, can cause significant hemorrhage at the time
tem, and hepatic ­abnormalities. Rubella is rare with routine of delivery or uteroplacental insufficiency with growth
­vaccinations. Folate deficiency is most likely to be associated r­etardation before delivery. Placental causes of intrauterine
with neural tube defects. Dispermy is rare and can lead to growth retardation result in asymmetric growth retarda-
triploidy, a condition that rarely results in a live birth. Eryth- tion with sparing of the brain. The findings of trisomy 21
roblastosis fetalis leads to fetal anemia with congestive heart are subtle at birth, but typically include brachycephaly, not
failure and hydrops, but not to malformations. In the past, microcephaly.
thalidomide use was a cause of malformations (almost invari-
ably prominent limb deformities). Nondisjunctional events PBD9 454–455  BP9 247–248  PBD8 452  BP8 255
during meiosis in the maternal ova account for trisomies and
monosomies, many of which have associated cardiac defects, 10  A  Multiple fetal losses earlier in gestation suggest the
including ventricular septal defect (e.g., trisomy 21). This likelihood of a chromosomal abnormality—the mother or
mechanism is unlikely in paternal sperm, however, which are father may be the carrier of a balanced translocation. Cystic
constantly being produced in large numbers throughout life. fibrosis transmembrane conductance regulator (CFTR) gene mu-
tations may lead to cystic fibrosis, and like most inborn er-
PBD9 454  BP9 247  PBD8 451–452  BP8 255–256 rors of metabolism, with appearance of findings postnatally.
The maternal serum level of α-fetoprotein can help identify
8   D  This infant has a cleft lip, one of the most common fetal neural tube defects, but these defects are not a cause
congenital anomalies. The absence of other defects suggests of early fetal loss. Maternal HIV infection is not a cause of

C H A P T E R 1 0   Diseases of Infancy and Childhood 1 3 9

significant fetal loss. Because the mother is blood type A inborn errors of metabolism are usually not manifest until
positive, fetal loss with erythroblastosis fetalis is unlikely, after birth. Rh incompatibility is unlikely in a primigravida,
although other blood group incompatibilities potentially unless she received a prior incompatible blood transfusion,
may result in erythroblastosis fetalis. and results in fetal hydrops. Sudden infant death syndrome
occurs in infants 1 month to 1 year of age, and there are no
PBD9 452, 454  BP9 247–248  PBD8 450–451  BP8 241–242 associated pathologic abnormalities. Maternal hypertension
and convulsions should be present for a diagnosis of toxemia.
11  E  Though a specific genetic abnormality, such as a Trisomy 16 can be seen with first-trimester losses, and is not
chromosomal abnormality or single gene defect, may be associated with inflammation.
sought, unknown causes still account for 40% to 60% of birth
defects. This is particularly true with more common birth de- PBD9 456  BP9 249  PBD8 454  BP8 256–257
fects, such as those listed in this case, and when they do not
fit with a recognized pattern of defects suggesting a specific 15  D  Listeriosis can be a congenital infection. Although
syndrome. Environmental factors related to birth defects in- pregnant women may have only a mild diarrheal illness,
clude infections, maternal disease such as diabetes mellitus the organism can prove devastating to the fetus or neonate.
(not gestational diabetes), and teratogens, accounting for up Mini-epidemics of listeriosis are often linked to a contami-
to 10% of birth defects. Multifactorial causes from the influ- nated food source, such as dairy products, chicken, or hot
ence of multiple gene predispositions is the second most dogs. Neonatal meningitis can be caused by Listeria monocy-
likely cause for birth defects, at 20% to 25%. togenes. Cytomegalovirus and toxoplasmosis are most likely
to produce severe central nervous system damage. Group B
PBD9 454  BP9 247–249  PBD8 450  BP8 255 streptococcal infections most often infect the fetus near term
or peripartum. These organisms release a factor that inhibits
12  F  Maternal diabetes can result in hyperplasia of the fe- the neutrophilic chemotactic factor complement C5a, inhibi­
tal islets because of the maternal hyperglycemic environment. ting a suppurative response. Herpetic congenital infections
This can occur if gestational diabetes is present, or if the moth- typically are acquired via passage through the birth canal.
er has had diabetes mellitus before pregnancy. After birth, the Parvovirus infection may cause a severe fetal anemia.
hyperplastic islets continue to overfunction, resulting in neo-
natal hypoglycemia. Infants of diabetic mothers also tend to PBD9 366, 460–461  BP9 249  PBD8 361, 459  BP8 249
exhibit macrosomia because of the growth-promoting effects
of increased insulin levels. The other listed findings are more 1 6  A  About 10% of cytomegalovirus-infected neonates
characteristic of pancreatic disorders in adults. Neutrophilic have extensive infection with inclusions found in many or-
infiltration with necrosis and hemorrhage are characteristic of gans. Severe anemia and myocardial injury cause hydrops,
acute pancreatitis. A mass with irregular glands and abnor- and the brain is often involved. The renal tubular epithelium
mal nuclear features could be an adenocarcinoma. Amyloid can be infected, and large cells with inclusions can be seen
deposition in islets may be seen in some cases of type 2 dia- with urine microscopic examination in some cases. Cytomega-
betes mellitus. Extensive fibrosis and fatty replacement of the lovirus manifested in neonates may have been acquired trans-
pancreas is seen in patients with cystic fibrosis surviving for placentally, at birth, or in breast milk. Herpes simplex virus
decades. Infiltration of T cells into islets occurs with the insu- is usually acquired via passage through the birth canal and
litis that presages overt clinical type 1 diabetes mellitus. does not cause a periventricular leukomalacia. HIV infection
in utero does not produce marked organ damage. Parvovirus
PBD9 455  BP9 248  PBD8 1132  BP8 776–781 infection may cause a severe fetal anemia. Congenital rubella
manifests in the first trimester, often with cardiac defects.
1 3  C  The acute inflammation suggests a bacterial infec-
tion, and group B streptococcus, which can colonize the PBD9 457, 461  BP9 249  PBD8 353, 452  BP8 256
v­ agina, is a common cause for congenital infection at term.
The infection can develop quickly. Cytomegalovirus, syphi- 1 7  A  The only increased IgM titer, indicating recent in-
lis, and toxoplasmosis are congenital infections that can fection, is that for Toxoplasma. The fetal central nervous sys-
cause stillbirth, but they are more likely to be chronic and de- tem findings are consistent with congenital toxoplasmosis.
velop earlier in gestation. Herpetic infections are most likely Her increased IgG titers for CMV and HSV type 1 suggest
to be acquired by passage through the birth canal. past infection. Her positive rubella titer is consistent with
past immunization. Congenital HIV does not have signifi-
PBD9 364, 460–461  BP9 249  PBD8 359, 459  BP8 256, 262 cant effects on the fetus in utero. The likely route for her
recent Toxoplasma infection is ingestion of poorly cooked,
14  F  Preterm premature rupture of membranes accounts contaminated meat containing cysts of Toxoplasma gondii.
for 30% to 40% of preterm deliveries, and infection is often The other routes of infection listed are not characteristic for
the cause, with ascending infection often resulting in chorio- toxoplasmosis.
amnionitis and funisitis. This organism is found in the genital
tract of sexually active adults. Intrauterine infection results PBD9 457, 460  BP9 249  PBD8 459  BP8 255–256
in release of collagenases and elastases that promote rupture
of membranes and release of prostaglandins that induce 18  E  The infant is small for gestational age because of intra-
smooth muscle contraction and labor. Cystic fibrosis and uterine growth retardation (IUGR). The asymmetric growth

1 4 0 U N I T I   General Pathology

with normal head size suggests a maternal or placental cause after the 26th week of gestation. These cells can be recog-
in later gestation. Fetal problems, such as chromosomal ab- nized on electron microscopy by the presence of lamellar
normalities (Down syndrome), infections (cytomegalovirus), bodies filled with phospholipids. Surfactant production
and erythroblastosis, are likely to produce symmetric growth increases greatly after 35 weeks’ gestation. Other struc-
retardation. Fetal hydrops can accompany congenital infec- tures in the lung do not synthesize the phosphatidyl-
tions and erythroblastosis, which may artificially increase fetal choline and phosphatidylglycerol compounds that are
weight. Infants born to diabetic mothers are likely to be larger important in surfactant production for reducing alveolar
than normal (macrosomia) for gestational age. surface tension.

PBD9 456–457  BP9 249–250  PBD8 454–455  BP8 256–257 PBD9 457–458  BP9 250–251  PBD8 456–457  BP8 257–259

19  A  This infant is small for gestational age (SGA). Given 2 3  B  The immaturity of the fetal lungs before 35 to 36
that there are no other problems noted prepartum or post- weeks’ gestation can be complicated by lack of sufficient
partum, then maternal cigarette smoking is the likely culprit, surfactant to enable adequate ventilation after birth. This
and smoking also increases the risk for preterm premature can result in hyaline membrane disease, shown in the
rupture of membranes (PPROM). Placental causes for fetal f­igure. Tests on amniotic fluid before birth, including leci-
growth restriction (FGR) tend to spare the infant brain. Ge- thin-sphingomyelin ratio, fluorescence polarization, and
netic mosaicism of the placenta may lead to stillbirth as well lamellar body counts, are useful in predicting the degree of
as FGR. Preeclampsia complicates the pregnancy via mater- pulmonary immaturity. Fetal anemia leads to heart failure
nal hypertension, edema, and proteinuria. Toxoplasmosis is and pulmonary congestion. Maternal toxemia and congen-
a congenital infection that tends to cause abnormalities of ital infections such as toxoplasmosis may lead to hyaline
the fetal brain, becoming apparent by the second trimester. membrane disease if the birth occurs prematurely as a con-
Triploidy and other fetal chromosomal abnormalities lead to sequence of these conditions, but they do not directly affect
multiple congenital anomalies. lung maturity. Oligohydramnios may result in neonatal
respiratory distress through the mechanism of pulmonary
PBD9 456–457  BP9 249–250  PBD8 454–456  BP8 256–257 hypoplasia.

20  B  The hyperinsulinism in the fetus of a diabetic mother PBD9 457–458  BP9 250–251  PBD8 456–457  BP8 257–259
suppresses pulmonary surfactant production. Corticoste-
roids stimulate surfactant production in type II pneumo- 24  E  Necrotizing enterocolitis is a complication of prema-
cytes. Infection may increase the risk of premature birth, but turity that is related to various factors, including intestinal
it does not significantly affect surfactant production. The risk ischemia, enterocyte apoptosis induced by platelet-activating
for major malformations, called diabetic embryopathy, is 6% to factor, bacterial overgrowth, and formula feeding. If severe,
10% in infants born to mothers with diabetes mellitus; but the wall of the intestine becomes necrotic and perforates,
there is no set pattern to the anomalies, and similar embry- necessitating surgical intervention. Duodenal atresia is
opathies are not seen in gestational diabetes. So the cause an uncommon congenital anomaly most often associated
for anomalies here is unknown. Macrosomia is the result of with trisomy 21; it leads to upper gastrointestinal obstruc-
growth-promoting effects of insulin in the fetus. Oligohy- tion and vomiting. Hirschsprung disease is a congenital
dramnios leads to constriction in utero that culminates in condition resulting from an aganglionic segment of distal
pulmonary hypoplasia, not decreased surfactant. Maternal colon; it leads to obstruction with distention, but not bloody
hypertension may reduce placental function and increase diarrhea. A Meckel diverticulum is a common anomaly and
growth retardation, but it typically does not have a signifi- is seen in about 2% of individuals. Typically, it is an inci-
cant effect on the production of surfactant. dental finding, although later in life it may be associated
with gastrointestinal tract bleeding if ectopic gastric mucosa
PBD9 455  BP9 250–251  PBD8 452  BP8 255, 257 is present within the diverticulum. Meconium ileus is seen
in the setting of cystic fibrosis and can lead to obstruction,
21  B  Sustained, high-dose oxygen therapy delivered but the infant typically does not pass stool. Pyloric stenosis
with positive pressure ventilation can cause injury to im- manifests at 3 to 6 weeks of life with projectile vomiting.
mature lungs, leading to the chronic lung disease known
as bronchopulmonary dysplasia. Pulmonary manifestations PBD9 459  BP9 252  PBD8 458  BP8 259
of cystic fibrosis are not seen at birth or in infancy. Mor-
tality from pulmonary hypoplasia is greatest at birth. In 25  D  The neonate most likely has hyaline membrane
sudden infant death syndrome, no anatomic abnormalities ­disease from fetal lung immaturity and lack of surfac-
are found at autopsy. A ventricular septal defect eventu- tant. Surfactant produced by type II pneumocytes consists
ally could lead to pulmonary hypertension from the left-to- predominantly of phospholipids-like lecithin contained
right shunt. in lamellar bodies released into alveoli. The adequacy of
s­ urfactant production can be gauged by the phospholipid
PBD9 459  BP9 251  PBD8 457–458  BP8 258 content of amniotic fluid because fetal lung secretions are
discharged into the amniotic fluid. Chromosomal analysis
22  E  Surfactant is synthesized by type II pneumo- may help to predict problems after birth or the possibility
cytes that line the alveolar sacs. They begin to differentiate of fetal loss. The Coombs test may help to determine the

C H A P T E R 1 0   Diseases of Infancy and Childhood 1 4 1

presence of erythroblastosis fetalis. Cystic fibrosis does 2 9  E  Twin–twin transfusion syndrome is the result of a
not cause respiratory problems at birth. The maternal se- vascular anastomosis between halves of a monochorionic
rum α-fetoprotein level is useful to predict fetal neural placenta. The donor twin typically is smaller, with reduced
tube defects and chromosomal abnormalities. organ function, including kidneys, and reduced amount of
amniotic fluid. The recipient twin becomes plethoric with
PBD9 457–458  BP9 250–251  PBD8 457  BP8 257–259 hydrops and increased amniotic fluid. The donor may also
become hydropic because of high-output heart failure from
2 6  A  This mild hemolytic anemia is most likely due to an the increased work of pumping blood into both twins. A
ABO incompatibility with maternal blood type O, which re- chromosomal aneuploidy is likely to affect just one of fra-
sults in anti-A antibody coating fetal cells. Most anti-A and ternal twins and could lead to hydrops, but the other twin
anti-B antibodies are IgM. In about 20% to 25% of pregnan- might not be affected. The other listed options should affect
cies, there are also IgG antibodies, which cross the placenta both twins similarly.
in sufficient titer to produce mild hemolytic disease in most
cases. The bilirubin concentration in the term infant in this PBD9 462  BP9 254–255  PBD8 461  BP8 261
case is not high enough to produce kernicterus. ABO incom-
patibilities are not likely to have such serious consequences 3 0  D  This is immune hydrops fetalis due to ABO incom-
for subsequent pregnancies as does Rh incompatibility. As patibility. Native populations of Mesoamerica and South
the infant matures, the level of maternal antibody dimin- America are almost exclusively blood group O. Although
ishes, hemolysis abates, and the infant develops normally. there are naturally occurring IgM isohemagglutinins
Resp­ iratory distress is unlikely at term because of appropri- against A and B blood group antigens, some women pro-
ate fetal lung maturity. duce IgG antibodies as well, which cross the placenta and
bind to fetal cells. Persons of European heritage are pre-
PBD9 461–462  BP9 254–255  PBD8 460–461  BP8 261–262 dominantly blood group A. In the clash of Old and New
worlds in the 16th century, populations of the latter fared
27  C  This infant has erythroblastosis fetalis, which results far worse. Rh incompatibility is more severe, but occurs after
when prior sensitization to a fetal blood cell antigen leads to the first pregnancy, when a fetal-maternal bleed can immu-
alloantibodies in maternal blood that can cross the placenta. nize the mother. However, the effects can be prevented
The Rh blood group system is most often implicated. The with Rho(D) immune globulin administered at birth. The P
maternal antibody coats fetal RBCs, causing hemolysis. The blood group antigen system may play a role in some hemo-
Coombs test is positive. The fetal anemia leads to congestive lytic anemias.
heart failure and hydrops. Hemolysis results in a very high
bilirubin level. A high maternal serum level of α-fetoprotein PBD9 461–462  BP9 254–255  PBD8 460–461  BP8 261–262
suggests a fetal neural tube defect; such defects are not as-
sociated with hydrops. Viral hepatitis is not a perinatal infec- 31  D  The erythroid precursors exhibit large, pink, in-
tion. Diminished glucocerebrosidase activity causes Gaucher tranuclear inclusions typical of parvovirus infection. In
disease, and this condition does not lead to perinatal liver adults, such an infection typically causes fifth disease,
failure or anemia. Listeriosis or other congenital infections which is self-limiting. This is one of the “O” infections in
may produce fetal hydrops and anemia, although not of the the TORCH mnemonic, however, describing congenital
severity described in this case. infections (toxoplasmosis, other infections, rubella, cyto-
megalovirus infection, and herpes simplex virus or HIV
PBD9 461–462  BP9 254–256  PBD8 460–461  BP8 261–262 infection). Parvovirus infection in the fetus can lead to a
profound fetal anemia with cardiac failure and hydrops
2 8  B  Nonimmune hydrops fetalis may be due to car- fetalis. Results of the Coombs test are negative, because
diac failure in utero, with cardiac defects leading to high- no antierythrocyte antibodies are involved. Congenital
output congestive heart failure. Cardiac defects may occur tumors are an uncommon cause of hydrops, and they
in a­ssociation with other anomalies and may be part of would produce a mass ­lesion, which was not described
c­hromosomal aneuploidies (chromosomes 13, 18, 21, and in this case. Cystic fibrosis does not affect erythropoiesis.
XO). A mass lesion with increased blood flow, such as a Although various chromosomal anomalies—monosomy
hemangioma, could lead to hydrops, but a neuroblastoma is X, in particular—may lead to hydrops, malformations are
unlikely to have markedly increased flow, or lead to a para- typical. Erythroblastosis fetalis from maternal IgG anti-
neoplastic effect with anemia. Cerebral lesions such as leuko- bodies directed at fetal RBCs is unlikely to occur in a first
malacia may be related to hydrops when due to a congenital pregnancy, and only erythroid expansion would be pres-
infection such as cytomegalovirus or toxoplasmosis (“C” and ent, not erythroid inclusions.
“T,” respectively, in the TORCH mnemonic), but the TORCH
titer results were negative in this case. A low-lying placenta PBD9 460, 462  BP9 256  PBD8 459  BP8 262–263
may lead to uteroplacental insufficiency with intrauterine
growth retardation, and predispose to placenta previa at the 3 2  F  Phenylketonuria (PKU) is caused by the absence of
time of birth. Splenomegaly is more likely to accompany im- functional phenylalanine hydroxylase genes and gives rise
mune hydrops, with marked extramedullary hematopoiesis. to hyperphenylalaninemia, which impairs brain develop-
ment and can lead to seizures. The block in phenylalanine
PBD9 462–463  BP9 254–255  PBD8 461–462  BP8 262–264 metab­olism results in decreased pigmentation of skin

1 4 2 U N I T I   General Pathology

and hair. It also results in the formation of i­ntermediate 3 5  D  In cystic fibrosis the elevated sweat chloride level is
compounds, such as phenylacetic acid, which are excreted related to a defect in the transport of chloride ions across epi-
in urine and impart to it a “mousy” odor. Although PKU thelia. The most common genetic defect is a deletion of three
is rare, because of the devastating consequences of this in- base pairs at the ΔF508 position coding for phenylalanine in
herited disorder, and because it can be treated with a phe- the cystic fibrosis transmembrane conductance regulator (CFTR)
nylalanine-free diet, this is one of the diseases for which gene. A frameshift mutation involves one or two base pairs,
screening is performed at birth. Adenosine deaminase de- not three, and changes the remaining sequence of amino acids
ficiency is a cause of severe combined immunodeficiency, in a protein. A point mutation may change the codon to the
which is character­ ized by multiple recurrent s­ evere infec- sequence of a “stop” codon, which truncates the protein being
tions from birth. α1-Antitrypsin deficiency may produce synthesized, typically leading to degradation of the protein.
cholestasis in children, but chronic liver disease develops A point mutation typically is a missense mutation that leads
later. Galactose-1-phosphate uridyltransferase deficiency to replacement of one amino acid for another in the protein
causes galactosemia, which is characterized by severe chain; this can lead to abnormal conformation and function of
liver disease and cataracts. Glucose-6-p­ hosphatase defi- the protein. A trinucleotide repeat sequence mutation leads
ciency causes type I glycogenosis (von Gierke disease), to amplification of repeats of three nucleotides, so-called tan-
which leads to liver failure. Lysosomal acid maltase dem repeats, which prevent normal gene expression.
deficiency causes Pompe disease, with features that include
cardiomegaly and heart failure. Sphingomyelinase defi- PBD9 466–471  BP9 223–226  PBD8 174, 466  BP8 264–267
ciency causes Niemann-Pick disease; affected infants have
marked hepatosplenomegaly and neurologic deterioration. 3 6  B  She has cystic fibrosis, due to inheritance of two abnor-
mal alleles for the cystic fibrosis transmembrane conductance regu-
PBD9 464–465  BP9 227–228  PBD8 463–464  BP8 234 lator (CFTR) gene. There are multiple mutations, which may
have different degrees of severity. The incidence in the United
33  E  Many persons with classic phenylketonuria (PKU) States is about 1 in 2500 live births, from a carrier rate of 1 in 25
have survived to adulthood because of newborn screening (this example makes the math easy). Autosomal dominant mu-
and dietary therapy. Insufficient phenylalanine hydroxylase tations tend to involve 50% of family members, and structural
leads to accumulation of phenylalanine, which is toxic to the proteins tend to be affected. Mitochondrial DNA is inherited
nervous system. Regardless of whether the developing fetus on the maternal side and affects mainly genes associated with
has this same deficiency, high maternal levels of phenylala- oxidative phosphorylation. Multifactorial inheritance does not
nine can affect the fetus. Thus a special maternal diet is indi- have a well-defined recurrence risk, but tends to run in fami-
cated, before and during pregnancy, and it has been suggested lies, and is more characteristic for diseases such as diabetes
that persons with PKU may remain on the special diet even af- mellitus or schizophrenia. X-linked recessive disorders are
ter childhood to reduce neurologic damage. The incidence of most likely to appear in males born to female carriers.
PKU in live births is 1 in 10,000 to 20,000 in the United States.
Incidence is probably a little higher in Argentina because the PBD9 466  BP9 223–226  PBD8 150–152  BP8 235–237
population is derived from the Mediterranean region, where
the prevalent mutation in the gene for phenylalanine hydrox- 3 7  C  With cystic fibrosis the abnormal chloride ion
ylase is different from the most common mutation in popula- transport results in abnormal mucous secretions in pancre-
tions of Northern Europe. The highest incidence is in Turkey, atic ducts. The secretions cause plugging with subsequent
at 1 in 2600. Because this is a treatable disorder in a planned acinar atrophy and fibrosis leading to malabsorption,
pregnancy, abortion is not the best option. Some inborn particularly of lipids. Abnormal fibrillin in elastic tissues
errors of metabolism may be treated with enzyme replace- is a feature of Marfan syndrome. Galactose-1-phosphate
ment following birth, but this is very expensive. Gene therapy uridyltransferase deficiency gives rise to galactosemia.
is experimental; bone marrow transplantation has been used Patients with this condition have liver damage, but no
in some cases of inherited enzyme disorders. There is no drug pancreatic abnormalities. Phenylketonuria results from a
therapy for PKU. deficiency of phenylalanine hydroxylase. Abnormalities of
the LDL receptor in familial hypercholesterolemia lead to
PBD9 464–465  BP9 227–228  PBD8 150–152  BP8 235–237 accelerated atherogenesis.

3 4  A  This infant has galactosemia, an inborn error of me- PBD9 467–469  BP9 223–227  PBD8 465–467  BP8 264–267
tabolism with an autosomal recessive pattern of inheritance.
Lactose in milk is a disaccharide that is converted by lactase to 3 8  D  With her classic history for cystic fibrosis (CF), genetic
glucose and galactose. An excess of galactose is toxic to liver, testing is most likely to reveal homozygosity for the ΔF508 mu-
brain, and eye. Affected infants begin to develop abnormali- tation of the cystic fibrosis transmembrane conductance regulator
ties as soon as they begin to ingest milk. Glucocerebrosidase (CFTR) gene. Biofilm formation in the airspaces has emerged
deficiency leads to Gaucher disease. Phenylalanine hydroxy- as a major factor in the ability of P. aeruginosa to evade anti-
lase deficiency leads to the classic form of phenylketonuria. bodies and antibiotics. The mucoid airway secretions create a
Sphingomyelinase deficiency leads to Niemann-Pick disease. hypoxic microenvironment in which the Pseudomonas organ-
UDP-glucuronosyltransferase deficiency is present in Gilbert isms produce alginate, a mucoid polysaccharide capsule that
syndrome. permits formation of a biofilm that lines airspaces and hides
bacteria inside it. Abnormal folding of CFTR is important in
PBD9 465–466  BP9 228  PBD8 150–152  BP8 235–237

C H A P T E R 1 0   Diseases of Infancy and Childhood 1 4 3

the overall pathogenesis of CF and is not specific to lung in- age, other factors listed increase the risk of SIDS. Male sex,
fection. Mutations in the transforming growth factor beta 1 African American race, low socioeconomic background
(TGFβ1) gene, when present along with CFTR mutations, of parents, lack of underlying medical problems, and ab-
are associated with several pulmonary phenotypes but are sence of anatomic abnormality all favor the likelihood of
not the cause of increased pathogenicity of Pseudomonas in- SIDS. The key factor that argues for SIDS in this case is
fections. CFTR also controls bicarbonate transport, particu- the lack of autopsy findings that support another diagno-
larly in the pancreas, but does not regulate bicarbonate sis. SIDS may relate to abnormalities of serotonergic neu-
secretion in lungs. Primary ciliary defects occur in Kartagener ral pathways in the medulla oblongata, and a respiratory
syndrome but not in CF; in CF ciliary defects are secondary to tract stressor (sleeping prone) may put vulnerable infants
viscid mucus production. at risk.

PBD9 469–471  BP9 223–227  PBD8 343, 465–470  BP8 266 PBD9 471–473  BP9 252–254  PBD8 471–473  BP8 259–261

39  D  These are manifestations of cystic fibrosis (CF), from 4 2  A  The most common tumor of infancy is a hemangi-
mutations in the cystic fibrosis transmembrane conductance oma, and these benign neoplasms form a large percentage
regulator (CFTR) gene. The chloride channel defect in sweat of childhood tumors as well. Although benign, they can be
ducts leads to concentration of sodium and chloride in sweat. large and disfiguring. Fibromatoses are fibromatous prolifer-
Note that some CFTR mutations lead to a “forme fruste” (at- ations of soft tissues that form solid masses. Lymphangioma
tenuated manifestation) of CF in which azoospermia may is another common benign childhood tumor seen in the neck,
be the only manifestation. An elevated hemoglobin A1c is a mediastinum, and retroperitoneum. Lymphoblasts as part of
feature of hyperglycemia with diabetes mellitus, but this is leukemic infiltrates or lymphomas are not likely to be seen in
a late finding in CF, because the islets of Langerhans are not skin, but mediastinal masses may be seen. A proliferation of
affected to the same degree as exocrine pancreas. Aminoac- neuroblasts occurs in neuroblastoma, a common childhood
iduria suggests galactosemia, which is most likely to become neoplasm in the abdomen.
apparent as hepatic failure in infancy. Hyperphenylalanin-
emia is a feature of phenylketonuria (PKU) manifested by PBD9 473–474  BP9 257–258  PBD8 473  BP8 267
mental retardation. VMA is increased in the urine of patients
with neuroblastoma. 4 3  C  Pediatric neoplasms are different from those in
adults and are far less common. The earlier in life the ma-
PBD9 466–468  BP9 223–227  PBD8 465–469  BP8 264–266 lignancy arises, the more likely it has features of primitive,
embryonic cells (blast cells). Hence, a tumor with the suf-
40  E  The most likely cause of death here is sudden in- fix -blastoma is likely a congenital or early childhood neo-
fant death syndrome (SIDS). Other causes of death must plasm. Adult neoplasia is often driven by environmental
be excluded by careful examination and interviews with influences (carcinogens, chronic infections) acting over
caretakers. By definition, there are no significant gross many years, and the most common neoplasms arise in
or microscopic autopsy findings. Infants with congenital epithelia (squamous and glandular). Sarcomas comprise a
anomalies or infections are unlikely to appear healthy, feed greater percentage of pediatric than adult neoplasms, but
well, or gain weight normally. Though the cause for SIDS they are unlikely to be congenital. Hematologic malignan-
is unknown, abnormalities of serotonergic neural pathways cies such as acute lymphocytic leukemia can be found in
in the medulla oblongata, and a respiratory tract stressor childhood.
(sleeping prone) may put vulnerable infants at risk. Ab-
normalities in medullary centers that regulate responses to PBD9 474–475  BP9 258  PBD8 474–475  BP8 268
noxious stimuli such as hypoxia, hypercarbia, and thermal
stress may lead to absence of cardiorespiratory and reflexive 44  E  Teratomas are benign neoplasms composed of
responses that normally maintain homeostasis. The other tissues derived from embryonic germ layers (ectoderm,
neurotransmitters listed are not implicated. Acetylcholine mesoderm, endoderm). Teratomas occur in midline loca-
acts at all preganglionic and postganglionic parasympa- tions, and the sacrococcygeal area pictured is the most
thetic neurons and at preganglionic sympathetic neurons. common. Less common immature, or frankly malignant,
Dopaminergic neurons are found in the substantia nigra. teratomas with neuroblastic elements can occur. Hamar-
GABAergic neurons have an inhibitory function on other tomas are masses composed of tissues normally found at
neurons in the central nervous system. Noradrenergic neu- a particular site, and they are rare. Hemangiomas form
rons originate in the locus ceruleus, and they comprise post- irregular, red-blue skin lesions that are flat and spread-
ganglionic sympathetic neurons as well. ing. Lymphangiomas in childhood are most often located
in the lateral head and neck region. Neuroblastomas are
PBD9 471–473  BP9 252–254  PBD8 471–473  BP8 260–261 malignant childhood tumors that most often arise in the
adrenal glands.
41  E  The cause of sudden infant death syndrome (SIDS)
is unknown, but certain demographic risk factors are well PBD9 475  BP9 258  PBD8 474  BP8 267–268
established. Among these is age. SIDS most often occurs
between 1 month and 1 year of age, and 90% of SIDS 45  D  This child has inherited an abnormal RB1 gene, and
deaths occur during the first 6 months of life. Along with early in life the other allele is lost, leading to loss of tumor

1 4 4 U N I T I   General Pathology

suppression and development of a retinoblastoma. About childhood neoplasm arising in the kidney. There is a dele-
60% to 70% of retinoblastomas are associated with germline tion of the short arm of chromosome 11 and contiguous loss
mutations. Aneuploidy usually results in fetal loss, although of neighboring genes. Loss of one allele of the Wilms tumor
monosomy X and trisomies 13, 18, and 21 occasionally may suppressor gene (WT1) leads to genitourinary defects and is
lead to live births. Chromosomal translocations may be seen the first “hit” in development of Wilms tumor. Deletion of
with other tumors, such as chronic myelogenous leukemia, one copy of the PAX6 gene leads to aniridia and to central
acute promyelocytic leukemia, and Burkitt lymphoma. Trinu- nervous system maldevelopment with mental retardation.
cleotide repeats are typically not associated with neoplasms. Renal anomalies, such as horseshoe kidney, can be seen in
Multifactorial inheritance may be associated with complex Edwards syndrome (trisomy 18), but not neoplasms. Like-
diseases, such as diabetes mellitus, hypertension, and bipolar wise, Marfan syndrome is not associated with an increased
disorder. Uniparental disomy is a mechanism for chromosom- risk of malignancy. The 47,XXY karyotype of Klinefelter
al imbalance, and neoplasia is unlikely. X-linked single-gene syndrome does not carry an increased risk of renal tumors.
defects are unlikely to lead to neoplasia. Patau syndrome (trisomy 13) is associated with many
anomalies, among them postaxial polydactyly and midline
PBD9 475  BP9 260–261  PBD8 475, 1365  BP8 270–271 defects that include cleft lip and palate, cyclopia, and holo-
prosencephaly. Turner syndrome (monosomy X) occurs in fe-
46  D  Amplification of the MYCN (NMYC) oncogene occurs males and can be associated with multiple anomalies, including
in about 25% of neuroblastomas, and the greater the number cystic hygroma, aortic coarctation, and renal anomalies.
of copies, the worse the prognosis. This amplification tends to
occur in neuroblastomas with a higher stage or with chromo- PBD9 479–481  BP9 261–263  PBD8 479–481  BP8 271–272
some 1p deletions. Hyperdiploidy or near-triploidy is usually
associated with lack of MYCN amplification, absence of 1p 48  C  Nephrogenic rests can be found in the renal paren-
deletion, and high levels of nerve growth factor receptor TrkA chyma adjacent to a Wilms tumor. They are presumed pre-
expression. All of these are associated with good prognosis. cursor lesions because they may share genetic alterations
Renal malformations are not related to neuroblastomas. The with the adjacent Wilms tumor. There is an increased risk
presence of ganglion cells is consistent with a better differen- of developing Wilms tumors in the contralateral kidney if
tiation and better prognosis; some tumors may differentiate such rests are present. Anaplasia in Wilms tumor suggests
over time and become ganglioneuromas under the influence a poor prognosis, but overall the cure rate is 90%. Gangli-
of TrkA. on cells and pseudorosettes are features of neuroblastoma.
Long-term survivors of Wilms tumor are at increased risk for
PBD9 475–479  BP9 258–260  PBD8 477–479  BP8 269–270 another malignancy, including a sarcoma, but the sarcoma is
not part of the original tumor.
4 7  F  WAGR syndrome is an uncommon condition that
carries an increased risk of development of Wilms tumor, a PBD9 480  BP9 262  BPD8 480–481  BP8 272

Deseases of UNIT
Organ Systems II



11C H A P T E R

Blood Vessels

PBD9 Chapter 11 and PBD8 Chapter 11: Blood Vessels

BP9 Chapter 9 and BP8 Chapter 10: Blood Vessels
  

1 A malignant neoplasm is found within the cranial cav- 4 A 73-year-old healthy man has experienced light-­
ity. A biopsy is obtained and microscopic examination shows headedness with episodes of fainting for the past 10 days. On
malignant cells within vascular lumina. Which of the fol- examination, his blood pressure changes from 135/90 mm Hg
lowing types of vessels is most likely to be invaded by this when lying down to 100/60 mm Hg when he assumes a sitting
malignancy? position. Laboratory studies show his serum electrolyte levels
A Arterioles are normal. Which of the following regulatory mechanisms for
B Capillaries blood pressure is most likely altered in this man?
C Lymphatics A Aldosterone release
D Muscular arteries B Cardiac output
E Veins C Intravascular volume
D Renin synthesis
2 A 44-year-old woman is found to have a blood pressure E Sympathetic tone
of 150/100 mm Hg on a routine physical examination follow- F Vasoconstriction
ing a transient ischemic attack (TIA). Laboratory studies show
normal serum potassium, sodium, and natriuretic peptide 5 A 55-year-old woman has had dull, episodic headaches
levels but increased plasma renin activity. Her urinary frac- for the past year, but otherwise she feels fine and has had no
tional excretion of sodium is normal. Which of the following major medical illnesses or surgical procedures during her
vascular abnormalities is most likely to be seen on renal arte- lifetime. On physical examination, her temperature is 37° C,
rial angiography? pulse is 70/min, respirations are 14/min, and blood pressure
A Arterial dissection is 166/112 mm Hg. Her lungs are clear on auscultation, and
B Arteriovenous fistula her heart rate is regular. An abdominal ultrasound scan shows
C Berry aneurysm that the left kidney is smaller than the right kidney. A renal an-
D Focal stenosis and dilation giogram shows a focal stenosis of the left renal artery. Which
E Vascularized mass lesion of the following laboratory findings is most likely to be pres-
ent in this patient?
3 A dermal venule with endothelial cells in the basal state A Anti–double-stranded DNA titer 1:512
is stressed by release of biogenic amines from mast cells fol- B C-ANCA titer 1:256
lowing anaphylaxis. The extravascular fluid compartment C increased cryoglobulins in blood
increases in size. Which of the following is the most likely D Plasma glucose level 200 mg/dL
change occurring in these activated endothelial cells? E Marked elevation in HIV RNA
A Cytoplasmic contraction F Plasma renin 15 mg/mL/hr
B Free radical formation
C mRNA translation
D Thromboxane synthesis
E VEGF elaboration

147

1 4 8 U N I T I I   Diseases of Organ Systems 9 A 61-year-old man has reported increasing fatigue over
the past year. Laboratory studies show a serum creatinine level
6 A clinical study is performed that includes a group of of 4.7 mg/dL and urea nitrogen level of 44 mg/dL. An abdom-
subjects whose systemic blood pressure measurements are inal ultrasound scan shows that his kidneys are symmetrically
consistently between 145/95 mm Hg and 165/105 mm Hg. smaller than normal. The representative high-magnification
They are found to have increased cardiac output and increased microscopic appearance of the kidneys is shown in the figure.
peripheral vascular resistance. Renal angiograms show no These findings are most likely to indicate which of the follow-
­abnormal findings, and CT scans of the abdomen show no ing underlying conditions?
masses. Laboratory studies show normal levels of serum cre- A Adenocarcinoma of the colon
atinine and urea nitrogen. The subjects take no medications. B Escherichia coli septicemia
Which of the following laboratory findings is most likely to be C Polyarteritis nodosa
present in this group of subjects? D Syphilitic endarteritis
A Decreased urinary sodium E Systemic hypertension
B Elevated plasma renin
C Hypokalemia 10 A 45-year-old man has had poorly controlled hyperten-
D Increased urinary catecholamines sion ranging from 150/90 mm Hg to 160/95 mm Hg for the
E Lack of angiotensin-converting enzyme past 11 years. Over the past 3 months, his blood pressure has
increased to 250/125 mm Hg. On physical examination, his
7 A 61-year-old woman has smoked two packs of cigarettes temperature is 36.9° C. His lungs are clear on auscultation, and
per day for the past 40 years. She has experienced increasing his heart rate is regular. There is no abdominal pain on pal-
dyspnea for the past 6 years. On physical examination, her vi- pation. A chest radiograph shows a prominent border on the
tal signs are temperature, 37.1° C; pulse, 60/min; respirations, left side of the heart. Laboratory studies show that his serum
18/min and labored; and blood pressure, 130/80 mm Hg. On creatinine level has increased during this time from 1.7 mg/dL
auscultation, expiratory wheezes are heard over the chest bi- to 3.8 mg/dL. Which of the following vascular lesions is most
laterally. Her heart rate is regular. A chest radiograph shows likely to be found in this patient’s kidneys?
increased lung volume, with flattening of the diaphragms, A Fibromuscular dysplasia
greater lucency to all lung fields, prominence of pulmonary B Granulomatous arteritis
arteries, and a prominent border on the right side of the heart. C Renal arterial stenosis
Laboratory studies include blood gas measurements of Po2 of D Necrotizing arteriolitis
80 mm Hg, Pco2 of 50 mm Hg, and pH of 7.35. Which of the fol- E Polyarteritis nodosa
lowing morphologic findings is most likely to be present in her
pulmonary arteries?
A Amyloid deposition
B Atheromatous plaques
C Intimal tears
D Medial calcific sclerosis
E Necrotizing vasculitis
F Phlebothrombosis
8 A population health study shows that the prevalence
of essential hypertension has been increasing for the past 10
years and now is found in one fourth of all adults. A strategy
is adopted to decrease the prevalence of hypertension through
lifestyle changes. A policy to reduce dietary intake of which of
the following is most likely to support this goal?
A Alcohol
B Animal protein
C Coffee
D Eggs
E Milk products
F Salt
G Sugar

  

C H A P T E R 1 1   Blood Vessels 149

11 A 57-year-old woman experiences mild intermittent 16 An experiment studies early atheroma development.
right hip pain after falling down a flight of stairs. Physical ex- Lipid streaks on arterial walls are examined microscopically
amination shows a 3-cm contusion over the right hip. The area and biochemically to determine their cellular and chemical
is tender to palpation, but she has full range of motion of the constituents and the factors promoting their formation. Early
right leg. A radiograph of the pelvis and right upper leg shows lesions show increased attachment of monocytes to endothe-
no fractures, but does show calcified, medium-sized arterial lium. The monocytes migrate subendothelially and become
branches in the pelvis. This radiographic finding is most likely macrophages; these macrophages transform themselves into
to represent which of the following? foam cells. Which of the following substances is most likely to
A An incidental observation be responsible for the transformation of macrophages?
B Benign essential hypertension A C-reactive protein
C Increased risk for gangrenous necrosis B Homocysteine
D Long-standing diabetes mellitus C Lp(a)
E Unsuspected hyperparathyroidism D Oxidized LDL
E Platelet-derived growth factor
12 A study of risk factors for atherogenesis in adults is per- F VLDL
formed. Chemical factors are found that are associated with
reduction in serum cholesterol. Which of the following sub- 17 A 29-year-old man has had angina for the past year.
stances is most likely to reduce serum cholesterol? There is a family history of cardiovascular disease. On exami-
A C-reactive protein nation, his blood pressure is 120/80 mm Hg. Laboratory stud-
B Homocysteine ies show total serum cholesterol 185 mg/dL and glucose 85
C Lipoprotein(a) mg/dL. A mutation involving a gene encoding for which of
D Omega-3 fatty acids the following is most likely present in this man’s family?
E trans–unsaturated fats A Angiotensin
B Apolipoprotein
13 A cohort study is performed involving healthy adult C Endothelin
men and women born 20 years ago. They are followed to assess D Factor VIII
development of atherosclerotic cardiovascular diseases. Multi- E Von Willebrand factor
ple laboratory tests are performed yearly during this study. An
increase in which of the following is most likely to indicate the 18 A study is conducted involving persons with LDL
greatest relative risk for development of one of these diseases? cholesterol levels above 160 mg/dL. They are found to have
A Anti–proteinase 3 (PR3) increased oxidized LDL deposited in their arteries. As a con-
B C-reactive protein (CRP) sequence the arterial lumen, particularly at branch points, is
C Cryoglobulin decreased in size. Which of the following is the most likely
D Erythrocyte sedimentation rate (ESR) pathologic change that develops initially in these areas of arterial
E Platelet count narrowing?
A Endothelial cell disruption
14 A 58-year-old man had a myocardial infarction 1 year ago, B Intimal thickening
which was the first major illness in his life. He now wants to pre- C Lymphocytic infiltrates
vent another acute coronary event and is advised to begin a pro- D Platelet aggregation
gram of exercise and to change his diet. A reduction in the level E Smooth muscle hypertrophy
of which of the following serum laboratory findings 1 year later
would best indicate the success of his diet and exercise regimen? 19 A 50-year-old man has a 2-year history of angina pecto-
A Calcium ris that occurs during exercise. On physical examination, his
B Cholesterol blood pressure is 135/75 mm Hg, and his heart rate is 79/min
C Glucose and slightly irregular. Coronary angiography shows a fixed
D Potassium 75% narrowing of the anterior descending branch of the left
E Renin coronary artery. He has several risk factors for atherosclerosis:
smoking, hypertension, and hypercholesterolemia. Which of
15 A 35-year-old woman has a reputation as a perfection- the following is the earliest event resulting from the effects of
ist. She has angina pectoris of 6 months’ duration. On physi- these factors?
cal examination, her blood pressure is 135/85 mm Hg. She is A Alteration in vasomotor tone regulation
168 cm (5 ft 5 in) tall and weighs 82 kg (BMI 29). Her Hgb B Conversion of smooth muscle cells to foam cells
A1C is 9% and fasting serum glucose is 143 mg/dL. Coronary C Dysfunction from endothelial injury
angiography shows 75% narrowing of the anterior descend- D Inhibition of LDL oxidation
ing branch of the left coronary artery and 70% narrowing of E Modification of hepatic lipoprotein receptors
the right coronary artery. Angioplasty with stent placement is   
performed. Which of the following is her greatest risk factor
for the causation of her disease?
A Age
B Diabetes mellitus
C Obesity
D Sedentary lifestyle
E Type A personality

1 5 0 U N I T I I   Diseases of Organ Systems

20 A 12-year-old boy died of complications of acute lym- 22 A 58-year-old woman has experienced chest pain at
phocytic leukemia. There is no family history of cardiovas- rest for the past year. On physical examination, her pulse is
cular disease. The gross appearance of the aorta at autopsy 80/min and irregular. The figure shows the microscopic ap-
is shown in the figure. Histologic examination of the linear pearance representative of her left anterior descending artery.
pale markings is most likely to show which of the following Which of the following laboratory findings is most likely to be
features? involved in the pathogenesis of the process illustrated?
A Cap of smooth muscle cells overlying a core of lipid A Elevated platelet count
B Low HDL cholesterol
debris C Low Lp(a)
B Collection of foam cells with necrosis and D Low plasma homocysteine
E Positive VDRL
calcification
C Granulation tissue with a lipid core and areas of 23 In an experimental model of atherosclerosis, plaques
are shown to change slowly but constantly in ways that can
hemorrhage promote clinical events, including acute coronary syndromes.
D Lipid-filled foam cells and small numbers of T In some cases, changes were not significantly associated with
acute coronary syndromes. Which of the following plaque al-
lymphocytes terations is most likely to have such an association?
E Cholesterol clefts surrounded by proliferating A Calcium deposition
B Hemorrhage into the plaque substance
smooth muscle cells and foam cells C Intermittent platelet aggregation
D Thinning of the media
21 A study of atheromatous plaques shows that release of E Ulceration of the plaque surface
growth factors, including PDGF, FGF, and TNF-α leads to in-
creased extracellular matrix production. As a result, the size 24 A 59-year-old woman with type II diabetes mellitus
of the plaques increases. Which of the following cells is most experiences an episode of chest pain with exercise. On ex-
likely to release these growth factors in the plaques? amination, her BMI is 30. Angiography reveals proximal
A Endothelium coronary arterial narrowing with up to 70% stenosis. Which
B Fibroblast of the following pharmacologic agents ingested in low doses
C Platelet daily is most appropriate for reducing her risk for myocardial
D Smooth muscle infarction?
E T lymphocyte A Acetaminophen
   B Aspirin
C Ibuprofen
D Paclitaxel
E Propranolol

C H A P T E R 1 1   Blood Vessels 151

25 An 84-year-old man with a lengthy history of smoking **
survived a small myocardial infarction 2 years ago. He now
reports chest and leg pain during exercise. On physical exami- 28 A 23-year-old man experiences sudden onset of severe,
nation, his vital signs are temperature, 37.1° C; pulse, 81/min; sharp chest pain. On physical examination, his temperature
respirations, 15/min; and blood pressure, 165/100 mm Hg. is 36.9° C, and his lungs are clear on auscultation. A chest ra-
Peripheral pulses are poor in the lower extremities. There is diograph shows a widened mediastinum. Transesophageal
a 7-cm pulsating mass in the midline of the lower abdomen. echocardiography shows a dilated aortic root and arch, with
Laboratory studies include two fasting serum glucose mea- a tear in the aortic intima 2 cm distal to the great vessels. The
surements of 170 mg/dL and 200 mg/dL. Which of the follow- representative microscopic appearance of the aorta with elas-
ing vascular lesions is most likely to be present in this patient? tic stain is shown in the figure. Which of the following diseases
A Aortic dissection is the most likely cause of these findings?
B Arteriovenous fistula A ANCA-associated vasculitis
C Atherosclerotic aneurysm B Diabetes mellitus, maturity onset type
D Polyarteritis nodosa C Marfan syndrome
E Takayasu arteritis D Scleroderma, diffuse
F Thromboangiitis obliterans E Systemic hypertension
   F Takayasu arteritis
29 A 59-year-old man experiences sudden severe chest pain
26 A 41-year-old man has had worsening abdominal pain that radiates to his back. On physical examination his blood
for the past week. On physical examination, his vital signs are pressure is 170/110 mm Hg. Heart sounds are distant. Pulsus
temperature, 36.9° C; pulse, 77/min; respirations, 16/min; and paradoxus is observed. A pericardiocentesis is performed and
blood pressure, 140/90 mm Hg. An abdominal CT scan shows yields blood. Which of the following pathologic findings has
the findings in the figure. Which of the following is the most most likely occurred in his aorta?
likely underlying disease process in this patient? A Aneurysm
A Diabetes mellitus B Arteriolosclerosis
B Marfan syndrome C Dissection
C Polyarteritis nodosa D Thrombosis
D Systemic lupus erythematosus E Vasculitis
E Syphilis 30 A 75-year-old man has experienced headaches for the past
27 A 77-year-old man has had progressive dementia and 2 months. On physical examination, his vital signs are tempera-
gait ataxia for the past 9 years. He succumbs to bronchopneu- ture, 37° C; pulse, 68/min; respirations, 15/min; and blood pres-
monia. Autopsy shows that the thoracic aorta has a dilated sure, 130/85 mm Hg. His right temporal artery is prominent,
root and arch, giving the intimal surface a “tree-bark” appear- palpable, and painful to the touch. His heart rate is regular, and
ance. Microscopic examination of the aorta shows an oblitera- there are no murmurs. His erythrocyte sedimentation rate is 100
tive endarteritis of the vasa vasorum. Which of the following mm/hr. A temporal artery biopsy is performed, and the seg-
laboratory findings is most likely to be recorded in this pa- ment of temporal artery excised is grossly thickened and shows
tient’s medical history? focal microscopic granulomatous inflammation. He responds
A Antibodies against Treponema pallidum well to corticosteroid therapy. Which of the following complica-
B Double-stranded DNA titer positive at 1:512 tions of this disease is most likely to occur in untreated patients?
C Ketonuria of 4+ A Blindness
D P-ANCA positive at 1:1024 B Gangrene of the toes
E Sedimentation rate of 105 mm/hr C Hemoptysis
   D Malignant hypertension
E Renal failure

1 5 2 U N I T I I   Diseases of Organ Systems nodules. A transbronchial lung biopsy specimen shows a nec-
rotizing inflammatory process involving the small peripheral
31 A 32-year-old woman has had coldness and numbness pulmonary arteries and arterioles. Which of the following is
in her arms and decreased vision in the right eye for the past the most likely diagnosis?
5 months. On physical examination, she is afebrile. Her blood A Granulomatosis with polyangiitis
pressure is 100/70 mm Hg. Radial pulses are not palpable, but B Fibromuscular dysplasia
femoral pulses are strong. She has decreased sensation and C Granuloma pyogenicum
cyanosis in her arms, but no warmth or swelling. A chest ra- D Kaposi sarcoma
diograph shows a prominent border on the right side of the E Polyarteritis nodosa
heart and prominence of the pulmonary arteries. Laboratory F Takayasu arteritis
studies show serum glucose, 74 mg/dL; creatinine, 1 mg/dL;
total serum cholesterol, 165 mg/dL; and negative ANA test 35 A 50-year-old man with muscle pain and fever for a
result. Her condition remains stable for the next year. Which month now notes darker colored urine for the past 2 weeks.
of the following is the most likely diagnosis? On physical examination he has palpable purpuric lesions
A Aortic dissection of his skin. Urinalysis shows hematuria and proteinuria. Se-
B Kawasaki disease rum laboratory findings include a mixed cryoglobulinemia
C Microscopic polyangiitis with a polyclonal increase in IgG, as well as a high titer of
D Syphilis anti–neutrophil cytoplasmic autoantibodies, mainly antimy-
E Takayasu arteritis eloperoxidase (MPO-ANCA, or P-ANCA). A skin biopsy is
F Thromboangiitis obliterans performed. What pathologic finding is most likely to be ob-
served in this biopsy?
32 A 43-year-old man has experienced malaise, fever, and A Giant cells and macrophages
a 4-kg weight loss over the past month. On physical examina- B Medial fibrinoid necrosis
tion, his blood pressure is 145/90 mm Hg, and he has mild dif- C Microabscesses
fuse abdominal pain, but no masses or hepatosplenomegaly. D Mycotic aneurysms
Laboratory studies include a serum urea nitrogen concentra- E Perivascular eosinophilic infiltrates
tion of 58 mg/dL and a serum creatinine level of 6.7 mg/dL.
Renal angiography shows right renal arterial thrombosis, and 36 A 33-year-old man has smoked two packs of cigarettes
the left renal artery and branches show segmental luminal nar- per day since he was a teenager. He has had painful thrombo-
rowing with focal aneurysmal dilation. During hemodialysis ses of the superficial veins of the lower legs for 1 month and
1 week later, he experiences abdominal pain and diarrhea and episodes during which his fingers become blue and cold. Over
is found to have melena. Which of the following serologic the next year, he develops chronic, poorly healing ulcerations
laboratory test findings is most likely to be positive in this of his feet. One toe becomes gangrenous and is amputated.
patient? Histologically, at the resection margin, there is an acute and
A ANA chronic vasculitis involving medium-sized arteries, with seg-
B C-ANCA mental involvement. Which of the following is the most ap-
C HIV propriate next step in treating this patient?
D HBsAg A Antibiotic therapy
E Scl-70 B Corticosteroid therapy
F RPR C Hemodialysis
D Insulin therapy
33 A 3-year-old child from Osaka, Japan, has developed E Smoking cessation
a fever and a rash and swelling of her hands and feet over
the past 2 days. On physical examination, her temperature 37 An 8-year-old child has had abdominal pain and dark
is 37.8° C. There is a desquamative skin rash, oral erythema, urine for 10 days. Physical examination shows blotchy purple
erythema of the palms and soles, edema of the hands and skin lesions on the trunk and extremities. Urinalysis shows he-
feet, and cervical lymphadenopathy. The child improves after a maturia and proteinuria. Serologic test results are negative for
course of intravenous immunoglobulin therapy. Which of the MPO-ANCA (P-ANCA) and PR3-ANCA (C-ANCA). A skin
following is most likely to be a complication of this child’s dis- biopsy specimen shows necrotizing vasculitis of small dermal
ease if it is untreated? vessels. A renal biopsy specimen shows immune complex de-
A Asthma position in glomeruli, with some IgA-rich immune complexes.
B Glomerulonephritis Which of the following is the most likely diagnosis?
C Intracranial hemorrhage A Giant cell arteritis
D Myocardial infarction B Henoch-Schönlein purpura
E Pulmonary hypertension C Polyarteritis nodosa
D Takayasu arteritis
34 A 50-year-old man has had a chronic cough for the past E Telangiectasias
18 months. Physical examination shows nasopharyngeal ul-
cers, and the lungs have diffuse crackles bilaterally on auscul-
tation. Laboratory studies include a serum urea nitrogen level
of 75 mg/dL and a creatinine concentration of 6.7 mg/dL. Uri-
nalysis shows 50 RBCs per high-power field and RBC casts.
His serologic titer for C-ANCA (proteinase 3) is ­elevated. A
chest radiograph shows multiple, small, bilateral pulmonary

C H A P T E R 1 1   Blood Vessels 153

38 A 35-year-old woman with a history of injection drug D Thrombosis of deep veins
use has developed a high fever over the past day. On exami- E Varicose veins
nation her temperature is 37.6° C. A heart murmur is auscul-
tated. Blood culture is obtained and grows Staphylococcus 42 A healthy 54-year-old woman has noted the increasing
aureus. She develops a severe headache. A head CT scan shows prominence of unsightly dilated superficial veins over both
an intracranial hemorrhage. Which of the following vascular lower legs for the past 5 years. Physical examination shows tem-
complications has most likely occurred in her brain? perature of 37° C, pulse of 70/min, respirations of 14/min, and
A Bacillary angiomatosis blood pressure of 125/85 mm Hg. There is no pain, swelling, or
B Hyperplastic arteriolosclerosis tenderness in either lower leg. Which of the following complica-
C Lymphangitis tions is most likely to occur as a consequence of her condition?
D Mycotic aneurysm A Atrophy of the lower leg muscles
E Phlebothrombosis B Disseminated intravascular coagulation
   C Gangrenous necrosis of the lower legs
D Pulmonary thromboembolism
39 A 60-year-old woman noted the change seen in the fig- E Stasis dermatitis with ulceration
ure while she was driving to work one morning. There was as-
sociated pain and numbness. Within 20 minutes after entering 43 A 48-year-old woman has developed persistent swelling
the warm office building, these problems disappeared. What and puffiness in the left arm after a mastectomy with axillary
pathologic process has most likely led to these findings? node dissection for breast cancer 1 year ago. She developed
A Calcification cellulitis in the left arm 3 months ago. Physical examination
B Hypertension shows firm skin over the left arm and “doughy” underlying
C Thrombosis soft tissue. The arm is not painful or discolored. Which of the
D Vasculitis following terms best describes these findings?
E Vasoconstriction A Lymphedema
40 A 21-year-old healthy woman, who is in week 34 of a B Subclavian arterial thrombosis
normal pregnancy, complains of itching with burning pain in C Thrombophlebitis
the perianal region for the past 4 months. She noted a small D Tumor embolization
amount of bright red blood on toilet paper last week. Which E Vasculitis
of the following underlying conditions is most likely to be
present in this patient? 44 A 50-year-old man cuts his right index finger on a sharp
A Filariasis metal shard while cleaning debris out of the gate in an irriga-
B Polyarteritis nodosa tion canal. The cut stops bleeding within 3 minutes, but 6 hours
C External hemorrhoids later he notes increasing pain in the right arm and goes to his
D Micronodular cirrhosis physician. On physical examination, his temperature is 38° C.
E Rectal adenocarcinoma Red streaks extend from the right hand to the upper arm, and
41 A 69-year-old woman has been bedridden while recu- the arm is swollen and tender when palpated. Multiple tender
perating from a bout of viral pneumonia complicated by bacte- lumps are noted in the right axilla. A blood culture grows group
rial pneumonia for the past 2 weeks. Physical examination now A β-hemolytic streptococcus. Which of the following terms best
shows some swelling and tenderness of the right leg, which describes the process that is occurring in this patient’s right arm?
worsens when she raises or moves the leg. Which of the follow- A Capillaritis
ing terms best describes the condition involving her right leg? B Lymphangitis
A Disseminated intravascular coagulation C Lymphedema
B Lymphedema D Phlebothrombosis
C Thromboangiitis obliterans E Polyarteritis nodosa
F Thrombophlebitis
G Varices

45 A 46-year-old man has noted increasing abdominal en-
largement over the past 15 months. Physical examination shows
multiple skin lesions on the upper chest that have central pul-
satile cores and measure, from core to periphery, 0.5 to 1.5 cm.
Pressing on a core causes a radially arranged array of subcu-
taneous arterioles to blanch. Laboratory studies show serum
glucose of 112 mg/dL, creatinine of 1.1 mg/dL, total protein
of 5.8 g/dL, and albumin of 3.4 g/dL. Which of the following
underlying diseases is most likely to be present in this patient?
A AIDS
B Diabetes mellitus
C Granulomatosis with polyangiitis
D Marfan syndrome
E Micronodular cirrhosis

1 5 4 U N I T I I   Diseases of Organ Systems

46 A 21-year-old woman is in the third trimester of an un-
complicated pregnancy. She has noted an enlarging nodule in
her mouth for the past 2 weeks. On physical examination there
is a 1-cm red nodule on the left lateral gingiva below the first
molar. The nodule regresses following delivery. What is this
nodule most likely to be?
A Bacillary angiomatosis
B Capillary hemangioma
C Cavernous lymphangioma
D Glomus tumor
E Kaposi sarcoma
  

47 A 10-year-old boy has a 2-cm spongy, dull red, circum- 49 A 35-year-old man is known to have been HIV-positive
scribed lesion on the upper outer left arm. The parents state for the past 10 years. Physical examination now shows mul-
that this lesion has been present since infancy, and the appear- tiple reddish purple, nodular skin lesions with the microscop-
ance has not appreciably changed. The lesion is excised, and ic appearance shown in the figure. These lesions have been
its microscopic appearance is shown in the figure. Which of slowly increasing for the past year. Which of the following risk
the following is the most likely diagnosis? factors is most likely to play a role in the development of these
A Angiosarcoma skin lesions?
B Hemangioma A Antiretroviral therapy
C Kaposi sarcoma B Epstein-Barr virus infection
D Lymphangioma C Hyperlipidemia
E Telangiectasia D Mycobacterium avium complex infection
   E Sexual intercourse

48 A 6-year-old previously healthy child has had increasing 50 A 67-year-old woman with glucose intolerance, hyperten-
size of his neck for the past year. Physical examination reveals sion, central obesity, and hyperlipidemia has increasing dyspnea
an ill-defined, soft mass deforming the left side of his neck, but from worsening congestive heart failure. Echocardiography
no other abnormalities. Surgical resection of the 10 cm mass is at- shows a left ventricular ejection fraction of 25%. Percutaneous
tempted, but the borders of the lesion are not discrete. Pathologic transluminal coronary angioplasty is performed with placement
examination of the resected tissue shows dilated spaces filled of a left anterior descending arterial stent containing paclitaxel.
with milky fluid and bounded by thin connective tissue walls. Which of the following long-term complications in her coronary
Microscopically, the spaces are lined by flattened endothelium artery is most likely to be prevented by paclitaxel?
and surrounded by collagenous tissue and smooth muscle with A Angiosarcoma
collections of small lymphocytes. Which of the following is the B Bacillary angiomatosis
most likely outcome associated with this child’s lesion? C Cystic medial degeneration
A Distant metastases D Giant cell arteritis
B Local recurrence E Proliferative restenosis
C More neoplasms elsewhere F Thromboangiitis obliterans
D Opportunistic infection
E Sarcomatous transformation 51 A 73-year-old woman with hyperhomocystinemia has
noted poor circulation in her left leg for the past 2 years. On
examination her dorsalis pedis and posterior tibial pulses are
barely palpable. CT angiography shows 90% stenosis of the
left iliac artery. Which of the following procedures would be
most effective in treating this woman?
A Arterial bypass graft
B Clopidogrel therapy
C Endovascular stent
D Synthetic graft
E Venous bypass graft

C H A P T E R 1 1   Blood Vessels 155

ANSWERS and arteriolar vasoconstriction can adjust blood pressure
and flow quickly, though the speed and magnitude of this
1   E  Veins have thin walls compared to their diameter, response is diminished with aging. Adjustments in the syn-
with less distinct layers, and slow blood flow. These charac- thesis and release of hormones such as renin and aldoste-
teristics make them more prone to compression and invasion rone take days.
by malignancies. This is a route for metastases via hematog-
enous spread. Of the remaining options, lymphatic invasion PBD9 488–489  BP9 330–332  PBD8 493–494  BP8 355–356
is an excellent choice, but the intracranial location chosen
for this question excludes lymphatics, which are extracra- 5  F  This is a classic example of a secondary form of hy-
nial in the head. Neoplasms can elaborate growth factors to pertension for which a cause can be determined. In this case,
promote endothelial proliferation and capillary formation to the renal artery stenosis reduces glomerular blood flow and
form a stromal vascular supply for continued growth. Inva- pressure in the afferent arteriole, resulting in renin release
sion of a muscular artery by a neoplasm is a rare event. by juxtaglomerular cells. The renin initiates angiotensin
II–induced vasoconstriction, increased peripheral vascular
PBD9 483–485  BP9 328–329  PBD8 488–489  BP8 340–341 resistance, and increased aldosterone, which promotes sodi-
um reabsorption in the kidney, resulting in increased blood
2  D  Fibromuscular dysplasia (FMD) typically involves volume. Anti–double-stranded DNA is a specific marker for
renal and carotid arteries. Renal arterial stenosis activates systemic lupus erythematosus. Anti–neutrophil cytoplasmic
the renin-angiotensin system, leading to hypertension. On autoantibodies (ANCAs) are markers for some forms of vas-
a­ ngiography, FMD appears as a “string of beads” caused by culitis, such as microscopic polyangiitis or ­ANCA-associated
focal medial hyperplasia with thickened fibromuscular ridg- vasculitis. Some patients with hepatitis B or C infection can
es adjacent to less involved areas of the arterial wall. This develop a mixed cryoglobulinemia with a polyclonal increase
is a surgically correctible cause for hypertension. Arterial in IgG. Renal involvement in such patients is common, and
dissection is most likely to occur in the proximal aorta with cryoglobulinemic vasculitis then leads to skin hemorrhages
risk factors of hypertension and cystic medial degeneration. and ulceration. Hyperglycemia is a marker for diabetes melli-
Arteriovenous fistulas and berry aneurysms are likely to be tus, which accelerates the atherogenic process and can involve
i­ntracranial and may rupture and bleed. Renal cell carcino- the kidneys, usually bilaterally, promoting the development
mas may be highly vascular, but a focal mass effect is unlike- of hypertension. HIV infection is not related to hypertension.
ly to obstruct the main renal artery, and does not account for
the TIA. Hypertension could eventually drive atherosclero- PBD9 490–491  BP9 331–333  PBD8 495  BP8 355–356
sis with arterial stenotic lesions lacking focal dilation.
6  A  The term essential hypertension (now applied when
PBD9 485  BP9 329–330  PBD8 490  BP8 341 there is no obvious cause for moderate hypertension) was
coined before hormonal control of blood pressure was un-
3   A  Activated endothelium can undergo many changes. derstood, because it was thought that the high pressure was
In the acute situation of anaphylaxis, endothelial contrac- essential to force blood through narrowed arteries. Essential
tion within minutes leads to exudation of intravascular fluid hypertension has several postulated theories for its cause.
into the extravascular compartment to produce edema, but One theory is that there are defects in renal sodium homeo-
this is also quickly reversible, because no permanent vascu- stasis that reduce renal sodium excretion. The kidney retains
lar injury has occurred. Free radical formation is more typi- sodium with water, increasing intravascular fluid volume,
cal for endothelial dysfunction when stressors have acted which drives increased cardiac output. The increased car-
for months to years, as is the case with atherogenesis. En- diac output is compensated by increasing peripheral vas-
dothelial injury from inflammation over days may lead to cular resistance, causing an increase in blood pressure. If
up-regulation of protein synthesis and release of regulators angiotensin-converting enzyme (ACE) was absent, blood
of thrombogenesis. Vascular injury may promote vascular pressure would decrease because angiotensin I would not
endothelial growth factor (VEGF) formation, but in the basal be converted to angiotensin II (drugs that act as ACE inhibi-
state, procoagulants, anticoagulants, cytokines, and growth tors are antihypertensives). An elevated plasma renin level is
factors are elaborated at low levels and balance each other. typical of renovascular hypertension, which can occur with
narrowing of a renal artery. Hypertensive patients with
PBD9 486–487  BP9 329–330  PBD8 490–491  BP8 341–342 hypokalemia also can have hyperaldosteronemia, which can
be caused by an aldosterone-secreting adrenal adenoma.
4  C  Orthostatic hypotension is described. Diminished Increased urinary catecholamines can indicate increased
intravascular volume from fluid loss (sweating, urina- catecholamine output from a pheochromocytoma.
tion, vomiting, diarrhea) or from decreased intake of flu-
ids leads to dehydration. The other options listed cannot PBD9 487–490  BP9 331–333  PBD8 493–495  BP8 355–356
act quickly or forcefully enough to compensate for lack of
­intravascular fluid volume. Subtle changes in total body 7  B  The pulmonary vasculature is under much lower
water and salt that play a role in essential hypertension pressure than the systemic arterial circulation and is much
are not reflected in altered electrolytes. Vomiting and diar- less likely to have endothelial damage, which promotes
rhea could alter acid-base status and electrolytes, but that
is not the case here. Autoregulation by sympathetic tone

1 5 6 U N I T I I   Diseases of Organ Systems

atherogenesis. Atherosclerosis in systemic arteries is most 10  D  Malignant hypertension can suddenly compli-
likely to occur where blood flow is more turbulent, a situa- cate and be superimposed on less severe, benign essential
tion that occurs at arterial branch points, such as in the first hypertension. The arterioles undergo concentric thick-
few centimeters of the coronary arteries or in the abdominal ening and luminal ­narrowing with malignant hyperten-
aortic branches. Factors driving systemic arterial atheroscle- sion, called hyperplastic arteriolosclerosis, and fibrinoid
rosis (e.g., hyperlipidemias, smoking, diabetes mellitus, and necrosis is a prominent feature. Fibromuscular dysplasia
systemic hypertension) do not operate in the pulmonary arte- can involve the main renal arteries, with medial hyperpla-
rial vasculature. Pulmonary hypertension is the driving force sia producing focal arterial obstruction. This process can
behind pulmonary atherosclerosis, and it occurs as pulmonary lead to hypertension, but not typically malignant hyper-
vascular resistance increases, when the pulmonary vascular tension. A granulomatous arteritis is most characteristic
bed is decreased by either obstructive (e.g., emphysema, as in of anti–neutrophil cytop­lasmic autoantibody (ANCA)–
this patient) or restrictive (e.g., as in scleroderma with pulmo- associated granulomatous vasculitis, which often involves
nary interstitial fibrosis) diseases. Amyloid deposition usually the kidney but typically involves lung and other organs.
occurs in small vessels and is driven by underlying conditions Hyaline arteriolosclerosis is seen with long-standing essen-
such as multiple myeloma or chronic inflammatory diseases. tial hypertension of moderate severity. These lesions give
Intimal tears lead to arterial dissection. Mönckeberg arterio- rise to benign nephrosclerosis. The affected kidneys become
sclerosis is typically an incidental finding in systemic arteri- symmetrically shrunken and granular because of progres-
oles. Necrotizing vasculitis occurs in pulmonary vasculature sive loss of renal parenchyma and consequent fine scarring.
in association with anti–neutrophil cytoplasmic autoanti- Polyarteritis nodosa produces a vasculitis that can involve
body (ANCA)–associated granulomatous vasculitis. Phlebo- the kidney.
thrombosis occurs in peripheral veins and is a risk factor for
pulmonary thromboembolism. PBD9 487, 490  BP9 333–334  PBD8 496  BP8 355–356

PBD9 491  BP9 332, 484–485  PBD8 512–513  BP8 346–347 1 1  A  Older adults with radiographic evidence of calcified
arteries often have Mönckeberg arteriosclerosis, beginning in
8  F  It is very difficult to keep dietary intake of sodium un- the internal elastic lamina. This is a benign process that is a
der 2 g per day because processed and packaged foods have form of arteriosclerosis, often with no serious sequelae. The
considerable salt for both preservation and flavoring. Just 30 distal extremities, pelvis, thyroid, and breast regions are the
g of potato chips can have more than 150 mg of sodium. Even most common locations. Such focal peripheral arterial calcifi-
a single “healthy” can of soup may have half a gram of so- cation is far less likely to be a consequence of atherosclerosis,
dium! Reduced renal sodium excretion may initiate essential with diabetes mellitus or with hypercalcemia. Hypertension
hypertension. Decreased sodium excretion may lead sequen- is most likely to affect small renal arteries, with hyaline or
tially to an increase in fluid volume, increased cardiac out- hyperplastic arteriolosclerosis, and calcification is not a ma-
put, and peripheral vasoconstriction, thereby elevating blood jor feature, although hypertension also is a risk factor for
pressure. Increased salt intake potentiates hypertension. atherosclerosis.
Although alcohol intake may reduce atherogenesis, there is
increased risk for cardiomyopathy as well as liver disease. PBD9 491  BP9 335  PBD8 496  BP8 343  AP3 Fig 1-18
Reducing protein intake may help patients with chronic renal
failure. The caffeine in coffee has neuroendocrine effects, but 12  D  Think about a diet containing teleost fish, which con-
it is the milk and sugar added that may be most deleterious. tain oils that may be associated with lower cholesterol and
Eggs have cholesterol. Milk is a good source of calcium, but therefore may be are protective against atherogenesis. The
comes with saturated fats and cholesterol, thus increasing other listed options are associated with risk for atherosclero-
the risk for atherogenesis. Sugar (sucrose and fructose), with sis. C-reactive protein (CRP) is an acute phase reactant that
high glycemic index, is most likely to drive weight gain. increases in response to inflammatory cytokines, including
those released from cells within atheromatous plaques. Hy-
PBD9 490  BP9 333  PBD8 493–495  BP8 354–356 perhomocysteinemia is a risk factor independent of lipids
for atheroma formation. Lipoprotein(a) is a small LDL-like
9   E  The figure shows an arteriole with marked hyaline lipid particle that forms an insudate in arterial walls to drive
thickening of the wall, indicative of hyaline arteriolosclerosis. atherogenesis. Trans fats chemically altered via hydroge-
Diabetes mellitus also can lead to this finding, which is most nation make lipids last longer on the shelf and taste better,
often seen in kidneys. Sepsis can produce disseminated in- but are bad for you by increasing the ratio of LDL to HDL
travascular coagulation with arteriolar hyaline thrombi. The cholesterol.
debilitation that accompanies cancer tends to diminish the
vascular disease caused by atherosclerosis. Syphilis can cause PBD9 493  BP9 336–338  PBD8 497  BP8 345
a vasculitis involving the vasa vasorum of the aorta. Poly-
arteritis can involve large to medium-sized arteries in many 13  B  CRP is an acute phase reactant that increases in re-
organs, including the kidneys; the affected vessels show fibri- sponse to inflammation. It causes endothelial cell activation,
noid necrosis and inflammation of the wall (vasculitis). promotes thrombosis, and increases leukocyte adhesiveness
in developing atheromas. Because atherogenesis is partly an
PBD9 490–491  BP9 333–334  PBD8 495  BP8 356–357 inflammatory process, CRP is an independent predictor of

C H A P T E R 1 1   Blood Vessels 157

cardiovascular risk. PR3 is one type of anti–neutrophil cyto- 17  B  Lipoprotein(a) is an altered form of LDL cholesterol
plasmic autoantibody (ANCA) associated with some vascu- that has the apolipoprotein B-100 portion of LDL linked to
litides such as microscopic polyangiitis. Cryoglobulins may apolipoprotein A, and an increase in Lp(a) is independently
be found with some forms of immune complex–mediated a­ ssociated with a risk for endothelial dysfunction and athero-
vasculitis. The ESR (“sed rate”) is a nonspecific indicator of genesis. Apolipoprotein E promotes metabolism and clear-
inflammation and therefore the internist’s least favorite test; ance of LDL. Drugs such as statins that affect LDL receptor
the ESR is best known to be markedly elevated with giant activity do not affect Lp(a) concentration. Early in the course
cell arteritis. Though platelets play a role in atheroma for- of atheroma formation, angiotensin and its receptor may
mation, the actual number of platelets is not a predictor of play a role in development of hypertension, which then be-
atherogenesis. comes a risk factor for atherosclerosis. Endothelin is a vaso-
constrictor with no known role in atherogenesis. Decreased
PBD9 493–494  BP9 337  PBD8 498  BP8 345 factor VIII leads to abnormal bleeding. Von Willebrand fac-
tor is required for normal platelet adhesion to collagen, and
14  B  Reduced cholesterol, particularly LDL cholesterol, its absence leads to abnormal bleeding.
with the same or increased HDL cholesterol level, indicates a
reduced risk of atherosclerotic complications. Atherosclero- BPD9 494–496  BP9 338–339  PBD8 497–498  BP8 345–347
sis is multifactorial, but modification of diet (i.e., reduction
in total dietary fat and cholesterol) with increased exercise is 1 8  B  The initial response of an arterial wall to injury is inti-
the best method of reducing risk for most individuals. Ath- mal thickening with neointimal smooth muscle cell prolifera-
eromatous plaques that have formed can be reduced, albeit tion and production of increased intimal extracellular matrix.
over months to years, but plaque regression yield an out- Note that “injury” can be caused by inflammation, immune
come better than drug or surgical therapy. Glucose is a mea- reactions, and toxins as well as the local physical trauma from
sure of control of diabetes mellitus. Potassium, calcium, and hypertension and abnormal flow. The trauma does not pro-
renin values can be altered with some forms of hypertension, duce immediate injury with endothelial cellular disruption,
one of several risk factors for atherosclerosis. but a response of endothelial dysfunction that signals smooth
muscle cell migration. This process takes years to show chang-
PBD9 492–493  BP9 336–338  PBD8 500  BP8 345–346 es of vascular narrowing. As atheromatous plaques progress,
there is participation by lymphocytes producing cytokines, as
15  B  Diabetes mellitus, suggested here by hyperglyce- well as monocytes that are transformed to macrophages that
mia, is a significant risk factor for early, accelerated, and accumulate lipid to evolve into foam cells. Eventually plaque
advanced atherosclerosis. If a premenopausal woman or a disruption may incite platelet aggregation.
young man has severe coronary atherosclerosis, diabetes
mellitus or other metabolic disease such as hyperlipidemia PBD9 494–496  BP9 334–335  BPD8 499  BP8 342
must be suspected as a predisposing factor. “Soft” risk fac-
tors that can play a lesser role in the development of athero- 1 9  C  Atherosclerosis is thought to result from an initial
sclerosis include obesity, stress, and lack of exercise. endothelial injury and the subsequent chronic inflammation
and repair of the arterial intima. All risk factors, including
PBD9 493–494  BP9 336–338  PBD8 497–498  BP8 343, 345 smoking, hyperlipidemia, and hypertension, cause biochem-
ical or mechanical injury to the endothelium with resulting
16  D  Oxidized LDL can be taken up by a special “scaven- dysfunction that initiates smooth muscle migration with pro-
ger” pathway in macrophages; it also promotes monocyte liferation, as well as lymphocyte and monocyte-macrophage
chemotaxis and adherence. Macrophages taking up the lipid infiltration. Formation of foam cells occurs after the initial
become foam cells that begin to form the fatty streak. Smok- endothelial injury. Vasomotor tone does not play a major
ing, diabetes mellitus, and hypertension all promote free radi- role in atherogenesis. Inhibition of LDL oxidation should di-
cal formation, and free radicals increase degradation of LDL minish atheroma formation. Although lipoprotein receptor
to its oxidized form. About one third of LDL is degraded to the alterations can occur in some inherited conditions, these ac-
oxidized form; a higher LDL level increases the amount of ox- count for only a fraction of cases of atherosclerosis, and other
idized LDL available for uptake into macrophages. C-reactive lifestyle conditions do not affect their action.
protein is a marker for inflammation, which can increase with
more active atheroma and thrombus formation and predicts PBD9 494–496  BP9 335–340  PBD8 499  BP8 342, 346–348
a greater likelihood of acute coronary syndromes. Increased
homocysteine levels promote atherogenesis through endothe- 2 0  D  The slightly raised, pale lesions shown in the figure
lial dysfunction. Lp(a), an altered form of LDL that contains are called fatty streaks and are seen in the aorta of almost all
the apo B-100 portion of LDL linked to apo A, promotes lipid children older than 10 years. They are thought to be precur-
accumulation and smooth muscle cell proliferation. Platelet- sors of atheromatous plaques. T cells are present early in the
derived growth factor promotes smooth muscle cell prolifera- pathogenesis of atherosclerotic lesions and are believed to ac-
tion. VLDL is formed in the liver and transformed in adipose tivate monocytes, endothelial cells, and smooth muscle cells
tissue and muscle to LDL. by secreting cytokines. T cells adhere to VCAM-1 on activat-
ed endothelial cells and migrate into the vessel wall. These
PBD9 496–497  BP9 338–340  PBD8 499–500  BP8 348–349 T cells, activated by some unknown mechanism, secrete

1 5 8 U N I T I I   Diseases of Organ Systems

various proinflammatory molecules that recruit and activate risk for hemorrhage that is associated with higher doses.
monocytes and smooth muscle cells and perpetuate chronic Acetaminophen is primarily analgesic in action. Ibuprofen
inflammation of the vessel wall. Fatty streaks cause no dis- is a nonsteroidal anti-inflammatory drug (NSAID) that has
turbances in blood flow and are discovered incidentally at no significant effect upon atheroma progression. Paclitaxel is
autopsy. All of the other lesions described are seen in fully one type of drug (initially used as an anticancer agent) used
developed atheromatous plaques. The histologic features of in drug-eluting stents placed in coronary arteries following
such plaques include a central core of lipid debris that can angioplasty to deter restenosis. Propranolol is a beta-blocker
have cholesterol clefts and can be calcified. There is usually that is employed as an antihypertensive agent.
an overlying cap of smooth muscle cells. Hemorrhage is a
complication seen in advanced atherosclerosis. Foam cells, PBD9  BP9 342–343  PBD8 498–499  BP8 347–348
derived from smooth muscle cells or macrophages that have
ingested lipid, can be present in all phases of atherogenesis. 2 5  C  Abdominal aneurysms are most often related to un-
derlying aortic atherosclerosis. This patient has multiple risk
PBD9 496–497  BP9 340–341  PBD8 502  BP8 346–350 factors for atherosclerosis, including diabetes mellitus, hy-
pertension, and smoking. When the aneurysm reaches this
2 1  D  Growth factor release from activated platelets, mac- size, there is a significant risk of rupture. An aortic dissection
rophages, and vascular wall cells induces smooth muscle cell is typically a sudden, life-threatening event with dissection
recruitment, medial smooth muscle migrate into the intima, of blood out of the ascending aortic lumen, typically into the
proliferate, and synthesize extracellular matrix (ECM) in much chest, without a pulsatile abdominal mass. The risk factors for
the same way that fibroblasts fill in a wound. Endothelial cell atherosclerosis and hypertension also underlie aortic dissec-
injury initiates atherogenesis, but endothelial cells do not form tion. An arteriovenous fistula can produce an audible bruit
a significant part of an atheroma. Platelets do not synthesize on auscultation. Classic polyarteritis nodosa (PAN) can pro-
ECM. T cells secrete inflammatory cytokines that activate mac- duce small microaneurysms in small arteries, most often re-
rophages, endothelial cells, and smooth muscle cells. nal and mesenteric. Takayasu arteritis typically involves the
aortic arch and branches in children. Thromboangiitis oblit-
PBD9 496–498  BP9 338–340  PBD8 499–501  BP8 348–349 erans (Buerger disease) is a rare condition in which muscular
arteries become occluded in the lower extremities in smokers.
2 2  B  The figure shows an arterial lumen that is markedly
narrowed by atheromatous plaque complicated by calcifica- PBD9 501–503  BP9 344–346  PBD8 707  BP8 357–359
tion. Hypercholesterolemia with elevated LDL and decreased
HDL levels is a key risk factor for atherogenesis. Although 26  A  His abdominal CT scan shows a 6-cm diameter enlarge-
platelets participate in forming atheromatous plaques, their ment of the abdominal aorta, which is an atherosclerotic ab-
number is not of major importance. Thrombocytosis can re- dominal aortic aneurysm. Diabetes mellitus, an important risk
sult in thrombosis or hemorrhage. Levels of Lp(a) and ho- factor for atherosclerosis, must be suspected if a younger man
mocysteine, if elevated, increase the risk of atherosclerosis. or premenopausal woman has severe atherosclerosis. Marfan
Syphilis (positive VDRL test result) produces endarteritis ob- syndrome is a risk for aortic dissection starting in a dilated as-
literans of the aortic vasa vasorum, which weakens the wall cending aorta. Polyarteritis nodosa does not typically involve
and predisposes to aortic aneurysm formation. the aorta. Obesity, a “soft” risk factor for atherosclerosis, also
contributes to type 2 diabetes mellitus; however, the extent of
PBD9 499–501  BP9 341–343  PBD8 503–504  BP8 350–352 atherosclerotic disease in this patient suggests early-onset dia-
betes mellitus, which is more likely to be type 1. Systemic lupus
2 3  D  Atheromatous plaques can be complicated by vari- erythematosus produces small arteriolar vasculitis. Syphilitic
ous pathologic alterations, including hemorrhage, ulceration, aortitis, a feature of tertiary syphilis, most often involves the
thrombosis, and calcification. These processes can increase thoracic aorta, but it is rare, and most thoracic aortic aneurysms
the size of the plaque and narrow the residual arterial lumen. nowadays are likely to be caused by atherosclerosis.
Although atherosclerosis is a disease of the intima, in ad-
vanced disease, the expanding plaque compresses the media. PBD9 498, 502–503  BP9 344–346  PBD8 507–508  BP8 358–359
This causes thinning of the media, which weakens the wall
and predisposes it to aneurysm formation. 2 7  A  This description is most suggestive of syphilitic aor-
titis, a complication of tertiary syphilis, with characteristic in-
PBD9 498–501  BP9 342–343  PBD8 503–504  BP8 348–351 volvement of the thoracic aorta. The history also suggests ta-
bes dorsalis and neurosyphilis. Obliterative endarteritis is not
2 4  B  Aspirin (acetylsalicylic acid) inhibits the cyclooxy- a feature of other forms of vasculitis. High-titer double-strand-
genase pathway of arachidonic acid metabolism and inhibits ed DNA antibodies are diagnostic of systemic lupus erythe-
platelets that participate in thrombogenesis. When athero- matosus, and the test result for P-ANCA (antibodies mainly
matous plaques have progressed to the point of symptom- directed at myeloperoxidase) is positive in various vasculiti-
atic occlusion and subsequent angina, they are likely to be des, including microscopic polyangiitis. Ketonuria can occur
unstable plaques that may rupture, ulcerate, or erode to pro- in individuals with diabetic ketoacidosis. A high sedimenta-
mote thrombosis. A “baby” aspirin containing 80 mg (325 tion rate is a nonspecific marker of inflammatory diseases.
mg in the “adult” tablet) taken once a day may reduce this
thrombotic risk, and also prevent the significantly increased PBD9 502, 504  BP9 345–346  PBD8 507–508  BP8 359–360

C H A P T E R 1 1   Blood Vessels 159

28  C  The figure shows disruption of the medial elastic fi- coronary arteritis with aneurysm formation and thrombosis,
bers, typical for cystic medial degeneration, which weakens skin rash, and lymphadenopathy. Microscopic polyangiitis
the aortic media and predisposes to aortic dissection. In a affects arterioles, capillaries, and venules with a leukocyto-
young patient a heritable disorder of connective tissues, such clastic vasculitis that appears at a similar stage in multiple
as Marfan syndrome, must be strongly suspected. Scleroder- organ sites (in contrast to classic polyarteritis nodosa, which
ma and anti–neutrophil cytoplasmic autoantibody (ANCA)– causes varying stages of acute, chronic, and fibrosing lesions
associated vasculitis (granulomatosis with polyangiitis) do in small to medium-sized arteries). Tertiary syphilis produces
not typically involve the aorta. Atherosclerosis associated an endaortitis with proximal aortic dilation. Thromboangi-
with diabetes mellitus and hypertension are risk factors for itis obliterans (Buerger disease) affects small to medium-
aortic dissection, although these are more often seen at an sized arteries of the extremities and is strongly associated
older age. Takayasu arteritis is seen mainly in children and with smoking.
involves the aorta (particularly the arch) and branches such
as the coronary and renal arteries, causing granulomatous PBD9 508–509  BP9 351  PBD8 513–514  BP8 364–365
inflammation, aneurysm formation, and dissection.
32  D  Classic polyarteritis nodosa (PAN) has segmental
PBD9 502, 504  BP9 346–348  PBD8 507  BP8 357, 361 involvement of medium-sized arteries with aneurysmal
dilation in the renal and mesenteric vascular beds (e.g.,
29  C  A sudden tear in the proximal aortic intima allows abdominal pain, melena). PAN can affect many organs at
blood to enter the space between layers within the wall of the different times. Although the cause of PAN is unknown,
aorta. This blood may pass through the aortic wall, around about 30% of patients have hepatitis B surface antigen that
great vessels, and into the pericardial cavity, as in this case presumably forms immune complexes that damage vascular
with cardiac tamponade. Blood may enter the chest cavity, walls. In contrast to microscopic polyangiitis, PAN has less
causing hemothorax. Hypertension is the most common risk of an association with anti–neutrophil cytoplasmic autoan-
factor for aortic dissection. In contrast, a false aneurysm is tibody (ANCA). A collagen vascular disease with a positive
characterized by formation of a hematoma by extravasated ANA test result, such as systemic lupus erythematosus, may
blood, but it communicates with the vascular lumen; a true produce a vasculitis, but not in the pattern seen here; the
aneurysm includes all three layers of the arterial wall. Arterio- affected vessels are smaller. Vasculitis with HIV infection is
losclerosis can be associated with hypertension, but it involves uncommon. The Scl-70 autoantibody is indicative of sclero-
arterioles, typically in kidneys, not the aorta. Thrombosis of derma, which can produce renal failure. The rapid plasma
extravasated blood from a dissection can occur, but this is not reagin (RPR) is a serologic test for syphilis; an endaortitis of
the primary lesion. Vasculitis does not often involve the aorta, the vasa vasorum can occur in syphilis.
but giant cell arteritis and Takayasu arteritis may do so, al-
though they are unlikely to weaken the wall to the point of PBD9 509–510  BP9 352  PBD8 514–515  BP8 363, 365–366
rupture.
3 3  D  Mucocutaneous lymph node syndrome, or Kawasaki
PBD9 504–505  BP9 346–348  PBD8 506, 509  BP8 358, 360 disease, involves large, medium-sized, and small arteries. Car-
diovascular complications occur in 20% of cases and include
3 0  A  Giant cell (temporal) arteritis typically involves thrombosis, ectasia, and aneurysm formation of coronary ar-
large to medium-sized external carotid artery branches in teries. Asthma can be seen in association with Churg-Strauss
the head (especially temporal arteries), but also vertebral vasculitis. Glomerulonephritis is a feature of anti–neutrophil
and ophthalmic arteries. Involvement of the latter can af- cytoplasmic autoantibody (ANCA)–associated granuloma-
fect vision. Because involvement of the kidney, lung, and tous vasculitis and of some autoimmune diseases such as
peripheral arteries of the extremities is much less common, systemic lupus erythematosus. Intracranial hemorrhage can
renal failure, hemoptysis, and gangrene of toes are unusual occur with septic emboli to peripheral cerebral arteries, pro-
complications of giant cell arteritis. There is no association ducing mycotic aneurysms that can rupture. Pulmonary hy-
between hypertension and giant cell arteritis, but some pa- pertension can also complicate Takayasu arteritis, but is not
tients may have polymyalgia rheumatica. as life-threatening as the coronary artery disease.

PBD9 507–508  BP9 350–351  PBD8 512–513  BP8 363–364 PBD9 510  BP9 352  PBD8 515  BP8 363, 366

31  E  Takayasu arteritis leads to “pulseless disease,” be- 3 4  A  Anti–neutrophil cytoplasmic autoantibody (ANCA)–
cause of involvement of the aorta (particularly the arch) and associated vasculitis (granulomatosis with polyangiitis) is a
branches such as coronary, carotid, and renal arteries, which form of hypersensitivity reaction to an unknown antigen char-
results in granulomatous inflammation, aneurysm forma- acterized by necrotizing granulomatous inflammation that typ-
tion, and dissection. Fibrosis is a late finding, and the pul- ically involves small to medium-sized vessels, although many
monary arteries also can be involved. Aortic dissection is an organ sites may be affected. Pulmonary and renal involvement
acute problem that, in older adults, is driven by atherosclero- can be life-threatening. C-ANCAs (antibodies mainly directed
sis and hypertension, although this patient is within the age against neutrophil proteinase 3) are found in more than 90%
range for complications of Marfan syndrome, which causes of cases. Fibromuscular dysplasia is a hyperplastic medial dis-
cystic medial degeneration of the aorta. Kawasaki disease af- order, usually involving renal and carotid arteries; on angiog-
fects children and is characterized by an acute febrile illness, raphy, it appears as a “string of beads” caused by thickened

1 6 0 U N I T I I   Diseases of Organ Systems

fibromuscular ridges adjacent to less involved areas of the are small vascular arborizations seen on skin or mucosal
arterial wall. Granuloma pyogenicum is an inflammatory re- surfaces.
sponse that can produce a nodular mass, often on the gingiva
or the skin. Kaposi sarcoma can produce plaquelike to nodular PBD9 512–513  BP9 349  PBD8 512, 517  BP8 366
masses that are composed of irregular vascular spaces lined by
atypical-appearing endothelial cells; skin involvement is most 38  D  Infectious endocarditis is likely present in this
common, but visceral organ involvement can occur. Polyar- woman, and portions of the vegetations often dislodge
teritis nodosa most often involves small muscular arteries, and and embolize. These are septic emboli carrying organisms
sometimes veins. It causes necrosis and microaneurysm for- that can start growing and produce local arterial destruc-
mation followed by scarring and vascular occlusion, mainly in tion wherever they are carried. The destruction of a vas-
the kidney, gastrointestinal tract, and skin of young to middle- cular wall by an infectious process is uncommon, but can
aged adults. Takayasu arteritis is seen mainly in children and result from spread of local infection or via embolization. A
involves the aorta (particularly the arch) and branches such as so-called mycotic aneurysm can be due to any infectious
the coronary and renal arteries, with granulomatous inflam- agent that weakens an ­arterial wall so that it bulges out—
mation, aneurysm formation, and dissection. an aneurysmal dilation. Bacillary angiomatosis produces
a focal vascular proliferation, typically on the skin, of an
PBD9 511–512  BP9 353–354  PBD8 516–517  BP8 363, 367–368 immunocompromised person infected with Bartonella spp.
Hyperplastic arteriolosclerosis is most often found in the
3 5  B  Microscopic polyangiitis involves small vessels, kidneys of persons with malignant hypertension, some of
typically capillaries. Kidneys and lungs are commonly in- whom may have underlying systemic sclerosis. Lymphatic
volved, but many organs can be affected. There may be an channels are not found within the brain. Phlebothrombosis
underlying immune disease, chronic infection, or drug reac- is typically found in large veins of the legs and pelvis, most
tion. Giant cell arteritis typically involves arterial branches of often following prolonged immobilization.
the external carotid, most often the temporal artery. Micro-
abscesses may be present with an infectious process, or with PBD9 502, 513  BP9 345, 355  PBD8 517  BP8 357, 369
thromboangiitis obliterans (Buerger disease), which typically
involves lower extremities. Mycotic aneurysms occur when 3 9  E  The “red, white, and blue” changes shown represent
a focus of infection, often from a septic embolus, weakens an Raynaud phenomenon, which can be a primary exaggerated
arterial wall so that it bulges out. Perivascular eosinophilic vasoconstriction without an underlying disease. In older
infiltrates may be seen with Churg-Strauss syndrome, which persons, an underlying disease, such as an autoimmune dis-
typically involves the lungs. ease, should be sought. Hyperviscosity may underlie this
phenomenon. In younger persons it is “primary” and likely
PBD9 510–511  BP9 353  PBD8 515-516  BP8 366-367 vasomotor hyperreactivity. Calcification with medial calcific
sclerosis tends to involve arteries that are small and muscu-
36  E  Thromboangiitis obliterans (Buerger disease), which lar, but larger than those of hands or feet; it is often an in-
affects small to medium-sized arteries of the extremities, is cidental finding on a radiograph. Hypertension may drive
strongly associated with smoking. This disease may eventu- atherosclerosis, but not marked vasoconstriction. Thrombo-
ally involve adjacent peripheral veins and nerves. Syphilis sis is unlikely to develop and subside so quickly. Vasculitis
can be treated with antibiotics, but it mainly produces an likewise is not an evanescent phenomenon.
aortitis. Immunosuppressive therapy is not highly effective.
Renal involvement does not occur. Although peripheral PBD9 513  BP9 355  PBD8 518  BP8 369–370
vascular disease with atherosclerosis is a typical finding in
diabetes mellitus, vasculitis is not. 40  C  The hemorrhoidal veins can become dilated from ve-
nous congestion. They are derived from ectoderm, covered
PBD9 512  BP9 354  PBD8 517  BP8 368 by squamous epithelium, and innervated by somatic sensory
nerves. External hemorrhoids are most common in patients
3 7  B  In children, Henoch-Schönlein purpura is the multi- with chronic constipation, but a pregnant uterus presses on
systemic counterpart of the IgA nephropathy seen in adults. pelvic veins to produce similar congestion, which promotes
The immune complexes formed with IgA produce the vascu- hemorrhoidal vein dilation. Filarial infections can affect lym-
litis that affects mainly arterioles, capillaries, and venules in phatics, including those in the inguinal region, and produce
skin, gastrointestinal tract, and kidney. In older adults, giant lymphedema. Polyarteritis does not affect veins. Portal hy-
cell arteritis is seen in external carotid branches, principally pertension with cirrhosis is most likely to dilate submucosal
the temporal artery unilaterally. Polyarteritis nodosa is seen esophageal veins, but internal hemorrhoidal veins occasion-
most often in small muscular arteries and sometimes veins, ally can be affected. Cirrhosis would be rare at this patient’s
with necrosis and microaneurysm formation followed by age. Carcinomas are also uncommon at this age, and they are
scarring and vascular occlusion. This occurs mainly in the not likely to obstruct venous flow.
kidney, gastrointestinal tract, and skin of young to middle-
aged adults. Takayasu arteritis is seen mainly in children and PBD9 514  BP9 356  PBD8 518–519  BP8 370
involves the aorta (particularly the arch) and branches such
as coronary and renal arteries, with granulomatous inflam- 41  D  Phlebothrombosis (but most often called thrombo-
mation, aneurysm formation, and dissection. Telangiectasias phlebitis) is a common problem that results from venous

C H A P T E R 1 1   Blood Vessels 161

stasis with prolonged immobilization. Phlebothrombosis small to medium-sized muscular arteries, typically the renal
may be a better (but less often used) term because there is and mesenteric branches. Varices are veins dilated from ob-
little or no inflammation, but the former term is well estab- struction to venous drainage.
lished. Disseminated intravascular coagulation more often
results in hemorrhage, and edema is not the most prominent PBD9 515  BP9 357  PBD8 519  BP8 371
m­ anifestation. Lymphedema takes longer than 2 weeks to de-
velop and is not caused by bed rest alone. Thromboangiitis 4 5  E  Spider telangiectasias are a feature of micronodu-
obliterans is a rare form of arteritis that results in pain and lar cirrhosis, typically as a consequence of chronic alcohol
ulceration of extremities. Varicose veins are dilated, tortuous abuse. They are thought to be caused by hyperestrogenism
superficial veins and can thrombose, but they are not related (estrogen excess) that results from hepatic damage with re-
to bed rest, and they do not predispose to pulmonary throm- duced clearance of circulating steroids. The most common
boembolism, as does thrombosis of deeper, larger veins. vascular skin lesion in patients with AIDS is Kaposi sarco-
ma, which is a neoplasm that manifests as one or more ir-
PBD9 514–515  BP9 356  PBD8 519  BP8 370–371 regular, red-to-purple patches, plaques, or nodules. Diabetes
mellitus, with its accelerated atherosclerosis, is most likely
4 2  E  Chronic peripheral venous stasis results in hemosid- to result in ischemia or gangrene. Vasculitis does not tend
erin deposition and dermal fibrosis with brownish discolor- to produce skin telangiectasias. The vascular involvement in
ation and skin roughening. Focal ulceration can occur over Marfan syndrome is primarily in the aortic arch with cystic
the varicosities, but extensive gangrene similar to that seen in medial degeneration.
arterial atherosclerosis does not occur. Hippocrates described
varicosities circa 370 bce and recommended compression for PBD9 515–516  BP9 357–358  PBD8 522  BP8 374
ulceration. In 1896 Australian surgeon Jerry Moore described
ligation of the great saphenous vein, a procedure still in use. 4 6  B  A so-called pyogenic granuloma is described. Half
The varicosities involve only the superficial set of veins, which of them are related to trauma and represent an exuberant
can thrombose, but they are not the source of thromboemboli, repair reaction with granulation tissue. They can ulcerate
as are the larger, deep leg veins. The varicosities do not affect and bleed. Bacillary angiomatosis represents a vascular
muscle; however, diminished muscular support for veins to proliferation that occurs in immunocompromised patients
“squeeze” blood out for venous return can predispose to for- infected with Bartonella organisms. Cavernous lymphangi-
mation of varicose veins. The thromboses in superficial leg omas can be deforming mass lesions in the neck region of
veins do not lead to disseminated intravascular coagulation, children, and though technically benign they do not have
because there is no acute vascular injury to promote ongoing well-defined borders and can be difficult to excise. A glo-
coagulopathy. Venous infarction is uncommon, because of mus tumor typically presents as a painful nodule beneath
collateral deep and superficial veins for venous return. the fingernail. There are various forms of Kaposi sarcoma
(classic, endemic, AIDS-related) but they all appear as red-
PBD9 514  BP9 356  PBD8 518–519  BP8 370 dish purple patches, plaques, or nodules on the skin and are
associated with Kaposi sarcoma herpes virus (KSHV), also
4 3  A  A mastectomy with axillary lymph node dissection called human herpesvirus 8 (HHV8).
leads to disruption and obstruction of lymphatics in the ax-
illa. Such obstruction to lymph flow gives rise to lymph- PBD9 516  BP9 358–359  PBD8 521  BP8 373
edema, a condition that can be complicated by cellulitis.
Arterial thrombosis produces ischemia distal to the obstruc- 4 7  B  The figure shows dilated, endothelium-lined spaces
tion. Thrombophlebitis from venous stasis is a complication filled with RBCs. The circumscribed nature of this lesion
seen more commonly in the lower extremities. An arterial and its long, unchanged course suggest its benign nature.
thrombosis can lead to a cold, blue, painful extremity. Tu- The vascular spaces of a hemangioma may be small, resem-
mor emboli are generally small but uncommon. Vasculitis bling capillaries, or large and cavernous. Angiosarcomas
is not a surgical complication. are large, rapidly growing malignancies in adults. Kaposi
sarcoma is uncommon in its endemic form in childhood,
PBD9 515  BP9 357  PBD8 519–520  BP8 371 and it is best known as a neoplastic complication associated
with HIV infection. Lymphangiomas, seen most often in
4 4  B  The red streaks represent lymphatic channels children, tend to be more diffuse and are not blood-filled. A
through which the acute infection is draining to axillary telangiectasia is a radial array of subcutaneous dilated arter-
lymph nodes, and these nodes drain to the right lymphatic ies or arterioles surrounding a central core that can pulsate.
duct and into the right subclavian vein (lymphatics from the
lower body and left upper body drain to the thoracic duct). PBD9 516–517  BP9 358–359  PBD8 523–524 521–522 
Capillaritis is most likely to be described with inflammation BP8 372–373
involving the lungs. Lymphedema occurs with blockage of
lymphatic drainage and develops over a longer period with- 4 8  B  The lesion is a cavernous lymphangioma. Although
out significant acute inflammation. Phlebothrombosis and histologically benign, such lesions have a tendency to
thrombophlebitis describe thrombosis in veins with stasis ­become large and extend around adjacent structures, com-
and minimal inflammation, typically in the pelvis and low- plicating removal. Lymphangiomas are unlikely to be asso-
er extremities. Classic polyarteritis nodosa (PAN) involves ciated with syndromes involving multiple neoplasms, and

1 6 2 U N I T I I   Diseases of Organ Systems

there is no association with infections. The cystic hygroma the lumen open and the paclitaxel limits smooth muscle
of Turner syndrome has a similar appearance, but is bilat- ­hyperplasia. Atherosclerosis is not a risk factor for neoplasia.
eral, nonprogressive, and may account for the “web neck” B­ acillary angiomatosis is caused by Bartonella organisms (cat-
appearance. scratch disease) and most often produces a red skin nodule.
Cystic medial degeneration is a feature of Marfan syndrome
PBD9 517  BP9 358–359  PBD8 522  BP8 373 with aortic dissection. Giant cell arteritis most often involves
external carotid branches such as temporal arteries; it is not
4 9  E  Infection by HHV8, also called Kaposi sarcoma herpes related to atherosclerosis. Thromboangiitis obliterans is a rare
virus (KSHV), is associated with Kaposi sarcoma (KS) and form of vasculitis involving lower extremities in smokers.
can be acquired as a sexually transmitted disease. KS is a
complication of AIDS. Individuals with HIV infection can PBD9 520–521  BP9 338, 362  PBD8 528  BP8 378
be infected with various viruses, including cytomegalovi-
rus (CMV) and Epstein-Barr virus (EBV), but these viruses 51  C  Endovascular stent placement can be done without
have no etiologic association with KS. EBV is a factor in the major surgery, because the graft can be deployed percuta-
development of non-Hodgkin lymphoma, and CMV can neously. Arterial bypass grafting is most often used from
cause pneumonitis or retinitis, or it can be disseminated. left internal mammary (thoracic) artery to left anterior de-
Hyperlipidemia may complicate antiretroviral therapy, but scending coronary artery, or by harvesting a portion of ra-
does not produce skin nodules. MAC infection can be seen dial artery to bypass a stenotic coronary artery. Clopidogrel
in HIV-infected patients as well, but it produces small gran- is an antiplatelet agent to help prevent thrombosis, and pa-
ulomas, mainly in tissues of the mononuclear phagocyte tients with such a risk, including severe atherosclerosis or
system. those with stent or graft placement, may receive such a drug.
Endovascular stents have largely replaced synthetic grafts,
PBD9 518–519  BP9 360–361  PBD8 523–524  BP8 375–376 which need major surgery for placement. Saphenous vein
bypass grafts are often used for coronary artery bypass graft-
50  E  She has metabolic syndrome, a risk for coronary ing. All of these grafts may be complicated by thrombosis,
atherosclerosis. Following angioplasty, there is often inti- restenosis, or both.
mal thickening that causes restenosis. The wire stent holds
PBD9 520–521  BP9 362–363  PBD8 526  BP8 377–378

12C H A P T E R

The Heart

PBD9 Chapter 12 and PBD8 Chapter 12: The Heart

BP9 Chapter 10 and BP8 Chapter 11: Heart
  

1 An 82-year-old woman has had increasing fatigue for sounds. On physical examination, pulse is 77/min and BP
the past 2 years. During this time, she has experienced par- is 110/80 mm Hg. He does not have anginal pain. His liver
oxysmal dizziness and syncope. On physical examination, span is increased to 14 cm. He has pitting edema to his knees.
she is afebrile. Her pulse is 44/min, respirations are 16/min, Jugular venous distention is noted to the angle of the jaw at
and blood pressure is 100/65 mm Hg. On auscultation, the 45-degree elevation of his head while lying down. Which of
lungs are clear, and no murmurs are heard. An echocardio- the following is most likely causing his heart disease?
gram shows a normal-sized heart with normal valve motion A Atrial myxoma
and estimated ejection fraction of 50%. After parasympathetic B Essential hypertension
(vagal) stimulation, the heart rate slows and becomes irregu- C Hyperlipidemia
lar. An abnormality involving which of the following is most D Rheumatic fever
likely to be present in this patient? E Smoking
A Atrioventricular node
B Bundle of His 4 A 62-year-old woman has had increasing dyspnea for
C Left bundle branch the past 2 years. She now awakens at night with air hunger
D Parasympathetic ganglion and cough productive of frothy sputum. On examination, she
E Right bundle branch has rales in all lung fields. Her point of maximal impulse is
F Sinoatrial node strong and displaced laterally. Echocardiography shows a de-
G Sympathetic ganglion creased ejection fraction of 30% with concentric increase in left
ventricular wall size. The valves appear normal. Which of the
2 A neonate developing normally has a newborn checkup. underlying diseases does she have?
On physical examination, there is a systolic murmur. Echocar- A Amyloidosis
diography reveals a muscular defect of the intraventricular B Cardiomyopathy
septum. A checkup 30 years later fails to reveal either a mur- C Hypertension
mur or a flow defect between the ventricles. Which of the fol- D Myocarditis
lowing cells most likely proliferated and led to disappearance E Pericarditis
of the defect?
A Adipocytes 5 A 41-year-old woman has been awakened at night with
B Conduction cells “air hunger” for the past year. She notes sleeping better while
C Endothelial cells sitting up in bed. Her serum B-type natriuretic peptide is >400
D Fibroblasts pg/mL (very high). What cardiac disease best explains her
E Mesothelial cells condition?
F Stem cells A Atrial myxoma
B Fibrinous pericarditis
3 A 66-year-old man has had cough and worsening short- C Giant cell myocarditis
ness of breath for 3 years. On examination, there is dullness D Libman-Sacks endocarditis
to percussion at both lung bases and poorly audible breath E Rheumatic valvulitis

163

1 6 4 U N I T I I   Diseases of Organ Systems 10 A 5-year-old child is not as active as other children his
age. During the past 8 months, the child has had multiple epi-
6 A 50-year-old man has had increasing abdominal dis- sodes of respiratory difficulty following exertion. On physical
comfort and swelling of his legs for the past 2 years. He has examination, his temperature is 37° C, pulse is 81/min, respi-
smoked cigarettes for 35 years. On physical examination, he rations are 19/min, and blood pressure is 95/60 mm Hg. On
has jugular venous distention, even when sitting up. The liver auscultation, a loud holosystolic murmur is audible. There
is enlarged and tender and can be palpated 10 cm below the are diffuse crackles over the lungs bilaterally, with dullness
right costal margin. Pitting edema is observed on the lower to percussion at the bases. A chest radiograph shows a promi-
extremities. A chest radiograph shows bilateral diaphragmat- nent left heart border, pulmonary interstitial infiltrates, and
ic flattening, pleural effusions, and increased lucency of lung blunting of the costodiaphragmatic recesses. The representa-
fields. Thoracentesis on the right side yields 500 mL of clear tive gross appearance of the child’s heart is shown in the fig-
fluid with few cells. Which of the following is most likely to be ure. Which of the following additional pathologic conditions
the underlying disease in this patient? would most likely develop in this child?
A Acute myocardial infarction A Aortic regurgitation
B Chronic bronchitis B Coronary atherosclerosis
C Primary pulmonary hypertension C Nonbacterial thrombotic endocarditis
D Pulmonary valve stenosis D Pulmonary hypertension
E Tricuspid valve stenosis E Restrictive cardiomyopathy

7 An infant born at term is noted to have cyanosis during 11 A 3-year-old child is developing normally. Physical
the first week of life. On examination a heart murmur is aus- examination reveals a low-pitched cardiac murmur. An echo-
cultated. Abnormal findings with echocardiography include cardiogram shows the presence of an ostium secundum, with
an overriding aorta, ventricular septal defect, right ventricular a 1-cm defect. Which of the following abnormalities is most
thickening, and pulmonic stenosis involving the fetal heart. likely to be found in this child?
This infant is most likely to have an inherited mutation involv- A Cyanosis at rest
ing which of the following genes? B Left-to-right shunt
A β-Myosin heavy chain (β-MHC) C Mural thrombosis
B Fibrillin 1 (FBN1) D Pericardial effusion
C KCNQ1 E Pulmonary hypertension
D NOTCH2
E Transthyretin (TTR)

8 Following an uncomplicated pregnancy, a term infant
appears normal at birth, but at 1 day of life the infant develops
respiratory distress. On physical examination the infant has
tachypnea, tachycardia, and cyanosis. There is an S1 ejection
click and a split S2 with prominent P sound. A radiograph
shows normal heart size but prominent hilar vascular mark-
ings. Echocardiography shows a small left atrium, large right
atrium, normally sized ventricles, widely patent foramen ova-
le, and normally positioned aorta and pulmonary trunk. What
type of congenital heart disease does this infant most likely
have?
A Atrial septal defect
B Coarctation of the aorta, preductal type
C Patent ductus arteriosus
D Tetralogy of Fallot
E Total anomalous pulmonary venous connection

9 A 77-year-old woman fell and fractured her ankle. She
has spent most of her time in bed for the past 16 days. She
develops sudden chest pain, dyspnea, and diaphoresis. On
examination she has left thigh swelling and tenderness. A
chest CT shows areas of decreased attenuation in the right and
left pulmonary arteries. A day later she has difficulty speak-
ing. MR angiography shows focal occlusion of a left middle
cerebral artery branch. Which of the following cardiac abnor-
malities is she most likely to have?
A Atrial myxoma
B Infective endocarditis
C Nonbacterial thrombotic endocarditis
D Patent foramen ovale
E Ventricular aneurysm
  

C H A P T E R 1 2   The Heart 165

12 A 2-year-old child had an illness 1 year ago character- 15 A 27-year-old woman gives birth to a term infant after
ized by a high fever. Staphylococcus epidermidis was cultured an uncomplicated pregnancy and delivery. The infant is cya-
from the blood. The child was given antibiotic therapy and notic at birth. Two months later, physical examination shows
recovered. Now on physical examination, a harsh, waxing the infant to be at the 37th percentile for height and weight.
and waning, machinery-like murmur is heard on auscultation The representative gross appearance of the infant’s heart is
of the upper chest. A chest radiograph shows prominence of shown in the figure. What is the most likely diagnosis?
the pulmonary arteries. Echocardiography shows all cardiac A Aortic stenosis
valves to be normal in configuration. Laboratory studies show B Pulmonic stenosis
normal arterial oxygen saturation level. Which of the follow- C Tetralogy of Fallot
ing congenital heart diseases is most likely to explain these D Transposition of the great vessels
findings? E Truncus arteriosus
A Aortic atresia
B Aortic coarctation 16 A 15-year-old boy complains of pain in his legs when he
C Atrial septal defect runs more than 300 m. Physical examination shows tempera-
D Patent ductus arteriosus ture, 36.8° C; pulse, 76/min; respirations, 22/min; and blood
E Tetralogy of Fallot pressure, 165/90 mm Hg. The radial pulses are 4+, and the
F Total anomalous pulmonary venous return dorsalis pedis pulses are 1+. Arterial blood gas measurement
shows a normal oxygen saturation level. Which of the follow-
13 A 5-year-old girl who is below the 5th percentile for ing congenital cardiovascular anomalies is most likely to be
height and weight for age has exhibited easily fatigability present in this patient?
since infancy. On physical examination, she appears cyanotic. A Aortic valve stenosis
Her temperature is 37° C, pulse is 82/min, respirations are B Coarctation of the aorta
16/min, and blood pressure is 105/65 mm Hg. Pulse oxi­metry C Patent ductus arteriosus
shows decreased oxygen saturation. One month later, she has D Transposition of the great arteries
fever and obtundation. A cerebral CT scan shows a right pari- E Tricuspid valve atresia
etal, ring-enhancing, 3-cm lesion. Which of the following con-
genital heart diseases is the most likely diagnosis?
A Atrial septal defect
B Bicuspid aortic valve
C Coarctation of the aorta
D Patent ductus arteriosus
E Truncus arteriosus
F Ventricular septal defect

14 In a clinical study of tetralogy of Fallot, patients are ex-
amined before surgery to determine predictors observed on
echocardiography that correlate with the severity of the dis-
ease and the need for more careful monitoring. A subset of
patients is found to have more severe congestive heart failure,
poor exercise tolerance, and decreased arterial oxygen satura-
tion levels. Which of the following is most likely to predict a
worse clinical presentation for these patients?
A Degree of pulmonary stenosis
B Diameter of the tricuspid valve
C Presence of an atrial septal defect
D Size of the ventricular septal defect
E Thickness of the left ventricle
  

1 6 6 U N I T I I   Diseases of Organ Systems 20 A 56-year-old man experiences episodes of severe sub-
sternal chest pain every time he performs a task that requires
17 A 21-year-old primigravida gives birth at term to a 2800- moderate exercise. The episodes have become more frequent
g infant with no apparent external anomalies. The next day, the and severe over the past year, but they can be relieved by sub-
infant develops increasing respiratory distress and cyanosis. lingual nitroglycerin. On physical examination, he is afebrile,
Echocardiography reveals a slitlike left ventricular chamber, his pulse is 78/min and regular, and there are no murmurs
small left atrium, and atretic aortic and mitral valves. Through or gallops. Laboratory studies show creatinine, 1.1 mg/dL;
which of the following structures could blood from the lungs glucose, 130 mg/dL; and total serum cholesterol, 223 mg/
most likely have reached the infant’s systemic circulation? dL. Which of the following cardiac lesions is most likely to be
A Anomalous venous return present in this man?
B Foramen ovale A Calcific aortic stenosis
C Patent ductus arteriosus B Coronary atherosclerosis
D Right fourth aortic arch C Restrictive cardiomyopathy
E Truncus arteriosus D Rheumatic mitral stenosis
F Ventricular septal defect E Serous pericarditis
18 A 60-year-old man has had angina on exertion for the F Viral myocarditis
past 6 years. A coronary angiogram performed 2 years ago
showed 75% stenosis of the left circumflex coronary artery 21 A retrospective study of myocardial infarction is per-
and 50% stenosis of the right coronary artery. For the past formed to analyze patterns of cardiac injury. One pattern of
3 weeks, the frequency and severity of his anginal attacks have injury involves the posterior left ventricular wall and septum.
increased, and pain sometimes occurs even when he is lying in Which of the following pathologic abnormalities is most likely
bed. On physical examination, his blood pressure is 110/80 mm to produce this pattern?
Hg, and pulse is 85/min with irregular beats. An ECG shows A Ascending aortic dissection
ST segment elevation. Laboratory studies show serum glucose, B Left anterior descending arterial plaque rupture
188 mg/dL; creatinine, 1.2 mg/dL; and troponin I, 1.5 ng/mL. C Left circumflex arterial vasculitis
Which of the following is most likely to explain these findings? D Right coronary sinus embolization
A Atheromatous plaque fissure with thrombosis E Right posterior descending arterial thrombosis
B Constrictive pericarditis with calcification   
C Endomyocardial fibrosis
D Extensive myocardial fiber hypertrophy
E Left ventricular mural thrombosis
F Mitral valve prolapse with regurgitation
  

19 A 37-year-old woman has the sudden onset of chest 22 A 48-year-old woman has had increasing dyspnea for
pain. On examination she is afebrile but tachycardic and hypo- the past 2 days. She experiences sudden cardiac arrest. The
tensive. An ECG shows ST segment elevation and pathologic representative light microscopic appearance of her left ven-
Q waves. The representative microscopic appearance of her tricular free wall is shown in the figure. Which of the following
left circumflex artery is shown in the figure. Which of the fol- is the most likely diagnosis?
lowing underlying conditions is she most likely to have? A Acute rheumatic myocarditis
A Acute myelogenous leukemia B Cardiomyopathy
B Chronic alcoholism C Myocardial infarction
C Diabetes mellitus D Septic embolization
D Marfan syndrome E Viral myocarditis
E Polyarteritis nodosa

C H A P T E R 1 2   The Heart 167

23 A study of ischemic heart disease analyzes cases of in- 27 A 69-year-old man with metabolic syndrome had chest
dividuals hospitalized with acute chest pain in which myo- pain and an elevated serum troponin I level 1 year ago. He
cardial infarction was documented at autopsy. The gross and was treated in the hospital with anti-arrhythmic agents for
microscopic appearances of the hearts are correlated with the 1 week. An echocardiogram showed an ejection fraction
degree of coronary atherosclerosis and its complications, clinical of 28%. He now has markedly reduced exercise tolerance.
symptoms, and therapies given before death. Hemorrhage and On physical examination, his temperature is 37° C, pulse is
contraction bands in necrotic myocardial fibers are most likely 68/min, respirations are 17/min, and blood pressure is
to be seen with infarction in which of the following settings? 130/80 mm Hg. Diffuse crackles are heard on auscultation of
A Acute coronary vasculitis the lungs. The representative gross appearance of his heart is
B Anti-arrhythmic drug usage shown in the figure. Which of the following complications of
C Angioplasty with stent placement this disease is the patient most likely to develop?
D Septic embolization A Atrial myxoma
E Thrombolytic therapy B Cardiac tamponade
C Constrictive pericarditis
24 A 50-year-old man with diabetes mellitus and hyperten- D Hypertrophic cardiomyopathy
sion has had pain in the left shoulder and arm for the past E Infective endocarditis
12 hours. Over the next 6 hours, he develops shortness of F Systemic thromboembolism
breath, which persists for 2 days. On day 3, he visits the phy-
sician. On physical examination, his temperature is 37.1° C, 28 A 72-year-old man with poorly controlled diabetes mel-
pulse is 82/min, respirations are 18/min, and blood pressure litus has worsening exercise tolerance for 5 years. For the past
is 160/100 mm Hg. Laboratory studies show total creatine year he has had chest pain with minimal exertion. On physi-
kinase (CK) activity within reference range, but the troponin cal examination he has bilateral pulmonary rales and pitting
I level is elevated. He continues to experience dyspnea for the edema of his legs. He has an irregular heart rate. A chest
next 3 days. On day 7 after the onset of shoulder pain, he has a radiograph shows prominent right and left heart borders. Echo-
cardiac arrest and is resuscitated. Cardiac imaging now shows cardiography shows decreased left ventricular ejection fraction
a large fluid collection around the heart. Which of the follow- (25%) with diminished wall motion. Laboratory studies show
ing complications has he most likely developed? an elevated serum B-type natriuretic peptide. Which of the fol-
A Aortic valvular perforation lowing pathologic findings is most likely present in this man?
B Hemopericardium A Critical coronary stenosis
C Left ventricular aneurysm B Left atrial mural thrombus
D Papillary muscle rupture C Hypertrophic cardiomyopathy
E Pericarditis D Mitral and tricuspid valve thickening
E Pericardial fibrinohemorrhagic exudate
25 A 45-year-old man experiences crushing substernal
chest pain after arriving at work one morning. Over the next
4 hours, the pain persists and begins to radiate to his left arm.
He becomes diaphoretic and short of breath, but waits until
the end of his 8-hour shift to go to the hospital. An elevated
serum value of which of the following laboratory tests would
be most useful for diagnosis of this patient on admission to the
hospital?
A ALT
B AST
C CK-MB fraction
D C-reactive protein
E LDH-1
F Lipase

26 A 19-year-old man suddenly collapses and is brought to
the emergency department. His vital signs are temperature,
37.1° C; pulse, 84/min; respirations, 18/min; and blood pres-
sure, 80/40 mm Hg. Laboratory findings include hemoglobin,
13.5 g/dL; platelet count, 252,000/mm3; WBC count, 7230/
mm3; serum glucose, 73 mg/dL; and creatinine, 1.2 mg/dL.
The total creatine kinase (CK) level is elevated, with a CK-MB
fraction of 10%. Which of the following underlying conditions
is most likely to be present in this patient?
A DiGeorge syndrome
B Down syndrome
C Familial hypercholesterolemia
D Hereditary hemochromatosis
E Marfan syndrome
  

1 6 8 U N I T I I   Diseases of Organ Systems 32 A 59-year-old man has experienced chronic fatigue for the
past 18 months. On physical examination, he is afebrile. A chest
29 A 68-year-old woman has had increasing dyspnea and radiograph shows bilateral pulmonary edema and a prominent
orthopnea for the past year. She does not report any chest left heart border. The representative gross appearance of his
pain. On physical examination, her temperature is 37° C, pulse heart is shown in the figure. Laboratory studies show serum
is 77/min, respirations are 20/min, and blood pressure is glucose, 74 mg/dL; total cholesterol, 189 mg/dL; total protein,
140/90 mm Hg. On auscultation of the chest, diffuse crack- 7.1 g/dL; albumin, 5.2 g/dL; creatinine, 6.1 mg/dL; and urea
les are heard in all lung fields. No murmurs or gallops are nitrogen, 58 mg/dL. What is the most likely diagnosis?
heard, and the heart rate is regular. A chest radiograph shows A Chronic alcoholism
prominent right and left heart borders. Coronary angiography B Diabetes mellitus
shows 90% occlusion of the left anterior descending artery. C Hemochromatosis
Echocardiography shows no valvular abnormalities, but there D Pneumoconiosis
is decreased left ventricular wall motion and an ejection frac- E Systemic hypertension
tion of 32%. Laboratory studies show serum glucose of 81 mg/   
dL, creatinine of 1.6 mg/dL, total cholesterol of 280 mg/dL,
triglyceride of 169 mg/dL, and troponin I of 1 ng/mL. Which 33 A 56-year-old man has worsening cough and orthopnea
of the following pharmacologic agents is most likely to be ben- for the past 2 years. On physical examination, he has dullness
eficial in the treatment of this patient? to percussion at both lung bases and diffuse crackles in the
A Amiodarone upper lung fields. He is afebrile. Echocardiography shows
B Alteplase marked left ventricular hypertrophy and severe aortic steno-
C Glyburide sis. The representative gross appearance of the opened heart
D Nitroglycerin is shown in the figure. A coronary angiogram shows no sig-
E Propranolol nificant coronary arterial narrowing. Which of the following
F Simvastatin underlying conditions best accounts for his findings?
A Congenital anomaly
30 A 50-year-old man has sudden onset of severe subster- B Diabetes mellitus
nal chest pain that radiates to the neck. On physical examina- C Infective endocarditis
tion, he is afebrile, but has tachycardia, hyperventilation, and D Marfan syndrome
hypotension. No cardiac murmurs are heard on auscultation. E Systemic hypertension
Emergent coronary angiography shows a thrombotic occlusion
of the left circumflex artery and areas of 50% to 70% narrowing
in the proximal circumflex and anterior descending arteries.
Which of the following complications of this disease is most
likely to occur within 1 hour of these events?
A Myocardial rupture
B Pericarditis
C Valvular insufficiency
D Ventricular fibrillation
E Thromboembolism

31 A study of persons receiving emergent medical services
is conducted. It is observed that 5% of persons with sudden
cardiac arrest who receive cardiopulmonary resuscitation sur-
vive. Which of the following is the most likely mechanism for
cardiac arrest in these survivors?
A Arrhythmia
B Infarction
C Inflammation
D Valve failure
E Ventricular rupture
  

C H A P T E R 1 2   The Heart 169

34 A 73-year-old woman had an episode a week ago in 36 A 65-year-old healthy woman has a check of her health
which she became disoriented, had difficulty speaking, and status and the only finding is a midsystolic click on ausculta-
had persisting weakness on the right side of her body. On phys- tion of the heart. Within 5 years she has increasing dyspnea.
ical examination, she is now afebrile with pulse of 68/min, res- Echocardiography now shows mitral regurgitation from pro-
pirations of 15/min, and blood pressure of 130/85 mm Hg. On lapse of a leaflet. Which of the following pathologic changes is
auscultation, the lungs are clear, the heart rate is irregular, and most likely present in this valve?
there is a midsystolic click. A chest CT scan shows a focus of A Destructive vegetations
bright attenuation within the heart. An echocardiogram shows B Dystrophic calcification
that one valvular leaflet appears to balloon upward. The ejec- C Fibrinoid necrosis
tion fraction is estimated to be 55%. Laboratory findings show D Myxomatous degeneration
serum creatine kinase (CK), 100 U/L; glucose, 77 mg/dL; E Rheumatic fibrosis
creatinine, 0.8 mg/dL; calcium, 8.1 mg/dL; and phosphorus,
3.5 mg/dL. Which of the following is the most likely diagnosis? 37 A 35-year-old woman has had palpitations, fatigue,
A Carcinoid heart disease and worsening chest pain during the past year. On physical
B Hyperparathyroidism examination, she is afebrile. Her pulse is 75/min, respirations
C Infective endocarditis are 15/min, and blood pressure is 110/70 mm Hg. Ausculta-
D Mitral annular calcification tion of the chest indicates a midsystolic click with late systolic
E Rheumatic heart disease murmur. A review of systems indicates that the patient has
F Senile calcific stenosis one or two anxiety attacks per month. An echocardiogram is
   most likely to show which of the following?
A Aortic valvular vegetations
35 A 77-year-old woman has had episodes of syncope B Mitral valve prolapse
with exertion for the past month. On physical examination, C Patent ductus arteriosus
she is afebrile. Her pulse is 66/min, respirations are 14/min, D Pulmonic stenosis
and blood pressure is 125/85 mm Hg. On auscultation, a sys- E Tricuspid valve regurgitation
tolic ejection murmur is heard. There are a few crackles over
the lung bases posteriorly. From the representative gross 38 An 11-year-old boy had a sore throat, no cough, tonsil-
appearance of the opened aorta shown in the figure, which of lar exudates, and 38.3° C fever 3 weeks ago, and a throat cul-
the following most likely contributed to the development of ture was positive for group A β-hemolytic Streptococcus. On
this lesion? the follow-up examination, the child is afebrile. His pulse
A Aging is 85/min, respirations are 18/min, and blood pressure is
B Atherosclerosis 90/50 mm Hg. On auscultation, a diastolic mitral murmur
C Chromosomal aneuploidy is audible, and there are diffuse rales over both lungs. Over
D Hypercalcemia of malignancy the next 2 days he has several episodes of atrial fibrillation
E Systemic lupus erythematosus accompanied by signs of acute left ventricular failure. Which
F Tertiary syphilis of the following pathologic changes occurring in this child’s
heart is most likely to be the cause of the left ventricular
failure?
A Amyloidosis
B Fibrinous pericarditis
C Mitral valve fibrosis
D Myocarditis
E Tamponade
F Verrucous endocarditis
  

1 7 0 U N I T I I   Diseases of Organ Systems

39 A 14-year-old girl has fever and chest pain 2 weeks after 41 A 25-year-old man was found dead at home by the
having a mild upper respiratory tract infection. On physical apartment manager, who had been called by the decedent’s
examination, her temperature is 37° C, pulse is 90/min, res- employer because of failure to report to work for the past
pirations are 20/min, and blood pressure is 85/45 mm Hg. 3 days. An external examination by the medical examiner
A friction rub is audible on auscultation of the chest. A chest showed splinter hemorrhages under the fingernails and no
radiograph shows pulmonary edema. An echocardiogram signs of trauma. The gross appearance of the heart at autop-
shows small vegetations at the closure line of the mitral and sy is shown in the figure. Which of the following laboratory
aortic valves. An endomyocardial biopsy shows focal intersti- findings is most likely to provide evidence for the cause of his
tial aggregates of mononuclear cells enclosing areas of fibri- disease?
noid necrosis. Her condition improves over the next month. A Elevated anti–streptolysin O titer
The representative gross appearance of the affected heart is B Positive ANCA serology
shown in the figure. Which of the following cardiac abnormal- C Increased creatine kinase–MB (CK-MB) fraction
ities is most likely to occur in this patient? D High double-stranded DNA autoantibody titer
A Constrictive pericarditis E Positive blood culture for Staphylococcus aureus
B Dilated cardiomyopathy
C Left ventricular aneurysm 42 A 22-year-old previously healthy man undergoes a tooth
D Myxoma extraction, and 4 days later he develops a fever. On physical
E Valvular stenosis examination his temperature is 37.6° C. A high-pitched systolic
murmur is auscultated. A tentative diagnosis of congenital
40 A 10-year-old girl develops subcutaneous nodules over heart disease is made. In which of the following locations is the
the skin of her arms and torso 3 weeks after a bout of acute congenital anomaly in this man most likely found?
pharyngitis. She manifests choreiform movements and begins A Ascending aorta
to complain of pain in her knees and hips, particularly with B Atrial appendage
movement. A friction rub is heard on auscultation of her chest. C Chordae tendineae
An abnormality detected by which of the following serum lab- D Cusps of valves
oratory findings is most characteristic of the disease affecting E Muscular septum
this girl?
A Antistreptolysin O antibody titer 43 A 26-year-old woman has had a fever for 5 days. On
B Antinuclear antibody titer physical examination, her temperature is 38.2° C, pulse is
C Creatinine level 100/min, respirations are 19/min, and blood pressure is
D Rapid plasma reagin test 90/60 mm Hg. A cardiac murmur is heard on auscultation.
E Troponin I level Her sensorium is clouded, but there are no focal neurologic
   deficits. Laboratory findings include hemoglobin, 13.1 g/dL;
platelet count, 233,300/mm3; and WBC count, 19,200/mm3.
Blood cultures are positive for gram-positive bacteria. Urinaly-
sis shows hematuria. An echocardiogram shows a 1.5-cm veg-
etation on the mitral valve. Which of the following conditions
is this patient most likely to develop?
A Cerebral arterial mycotic aneurysm
B Dilated cardiomyopathy
C Myxomatous mitral valve degeneration
D Pericardial effusion with tamponade
E Pulmonary abscess

C H A P T E R 1 2   The Heart 171

44 A 19-year-old man has had a low-grade fever for 48 A 50-year-old man with a history of infective endocar-
3 weeks. On physical examination, his temperature is 38.3° C, ditis has increasing fatigue. He receives a bileaflet tilting disk
pulse is 104/min, respirations are 28/min, and blood pressure mechanical mitral valve prosthesis. After surgery, he is stable,
is 95/60 mm Hg. A tender spleen tip is palpable. There are and an echocardiogram shows no abnormal valvular or ven-
splinter hemorrhages under the fingernails and tender hem- tricular function. Which of the following pharmacologic agents
orrhagic nodules on the palms and soles. A heart murmur should he receive regularly after this surgical procedure?
is heard on auscultation. Which of the following infectious A Aspirin
agents is most likely to be cultured from this patient’s blood? B Ciprofloxacin
A Coxsackievirus B C Cyclosporine
B Mycobacterium tuberculosis D Digoxin
C Pseudomonas aeruginosa E Propranolol
D Viridans streptococci F Warfarin
E Trypanosoma cruzi
49 A 44-year-old, previously healthy man has experienced
45 A 71-year-old woman has had a 10-kg weight loss worsening exercise tolerance accompanied by marked short-
accompanied by severe nausea and vomiting of blood for the ness of breath for the past 6 months. On physical examina-
past 8 months. On physical examination, she is afebrile. Labo- tion, his vital signs are normal. He has diffuse rales in all
ratory studies show hemoglobin, 8.4 g/dL; platelet count, lung fields and pitting edema to the knees. Laboratory stud-
227,100/mm3; and WBC count, 6180/mm3. Biopsy specimens ies show serum sodium, 130 mmol/L; potassium, 4 mmol/L;
obtained by upper gastrointestinal endoscopy show adeno- chloride, 102 mmol/L; CO2, 25 mmol/L; creatinine, 2 mg/dL;
carcinoma of the stomach. CT scan of the abdomen shows and glucose, 120 mg/dL. A 100-mL urine sample is collected.
multiple hepatic masses. CT scan of the head shows a cystic There is 1.3 mmol sodium and 40 mg creatinine in the urine
area in the right frontal lobe. Her condition is stable until sample. A chest radiograph shows cardiomegaly and pul-
2 weeks later, when she develops severe dyspnea. A chest CT monary edema with pleural effusions. An echocardiogram
scan shows areas of decreased pulmonary arterial attenua- shows four-chamber cardiac enlargement and mitral and
tion. Which of the following cardiac lesions is most likely to be tricuspid valvular regurgitation, with an ejection fraction of
present in this woman? 30%. A coronary angiogram shows less than 10% narrowing
A Calcific aortic valvular stenosis of the major coronary arteries. Which of the following is the
B Constrictive pericarditis most likely diagnosis?
C Epicardial metastatic carcinoma A Amyloidosis
D Left ventricular mural thrombosis B Hypercholesterolemia
E Nonbacterial thrombotic endocarditis C Familial cardiomyopathy
D Rheumatic heart disease
46 A 41-year-old woman has had increasing dyspnea for the E Trypanosoma cruzi infection
past week. On physical examination, temperature is 37.3° C,
pulse is 85/min, respirations are 20/min, and blood pressure 50 A 56-year-old man has experienced increased fatigue
is 150/95 mm Hg. There is dullness to percussion over the and decreased exercise tolerance for the past 2 years. On phys-
lung bases. A chest radiograph shows large bilateral pleural ical examination, his temperature is 37° C, pulse is 75/min,
effusions and a normal heart size. Laboratory findings in- respirations are 17/min, and blood pressure is 115/75 mm Hg.
clude serum creatinine, 3.1 mg/dL; urea nitrogen, 29 mg/dL; On auscultation, diffuse crackles are audible. The abdomen is
troponin I, 0.1 ng/mL; WBC count, 3760/mm3; hemoglobin, distended with a fluid wave, and there is bilateral pitting ede-
11.7 g/dL; and positive ANA and anti–double-stranded DNA ma to the knees. A chest radiograph shows pulmonary edema,
antibody test results. Which of the following cardiac lesions is pleural effusions, and marked cardiomegaly. An echocar-
most likely to be present in this patient? diogram shows mild tricuspid and mitral regurgitation and
A Calcific aortic stenosis reduced right and left ventricular wall motion, with an ejec-
B Hemorrhagic pericarditis tion fraction of 30%. He experiences cerebral, renal, and splen-
C Nonbacterial thrombotic endocarditis ic infarctions over the next year. Chronic use of which of the
D Libman-Sacks endocarditis following substances has most likely produced these findings?
E Mural thrombosis A Acetaminophen
F Rheumatic verrucous endocarditis B Cocaine
C Ethanol
47 A 44-year-old woman with rheumatic heart disease D Lisinopril
with aortic stenosis undergoes valve replacement with a bio- E Nicotine
prosthesis. She remains stable for the next 8 years and then F Propranolol
develops diminished exercise tolerance. Which of the follow-
ing complications involving the bioprosthesis has most likely
occurred?
A Embolization
B Hemolysis
C Myocardial infarction
D Paravalvular leak
E Stenosis

1 7 2 U N I T I I   Diseases of Organ Systems most likely show which of the following functional cardiac
disturbances?
51 A 25-year-old man suffers a sudden cardiac arrest. He is A Dynamic obstruction to ventricular outflow
resuscitated. On examination his vital signs are normal. Echo- B Impaired ventricular diastolic filling
cardiography shows that the left ventricle is normal but there C Increased end-systolic volume
is marked thinning with dilation of the right ventricle. MR im- D Mitral and tricuspid valvular insufficiency
aging of his chest shows extensive fibrofatty replacement of E Reduced ejection fraction
the myocardium, but no inflammation. Which of the following 55 A 33-year-old woman from Victoria, British Columbia,
is the most likely cause for his findings? goes to the physician because of increasingly severe dyspnea,
A Cardiomyopathy orthopnea, and swelling of the legs for the past 2 weeks. She
B Chagas disease has no previous history of serious illness or surgery. On physi-
C Hypertension cal examination, her temperature is 37.8° C, pulse is 83/min,
D Long QT syndrome respirations are 20/min, and blood pressure is 100/60 mm Hg.
E Radiation therapy An ECG shows episodes of ventricular tachycardia. An echo-
52 A 10-year-old girl who is normally developed has cardiogram shows right and left ventricular dilation, but no
chronic progressive exercise intolerance. On physical exami- valvular deformities. An endomyocardial biopsy shows focal
nation, temperature is 37.1° C, pulse is 70/min, respirations myocyte necrosis and lymphocytic infiltrate. Which of the fol-
are 14/min, and blood pressure is 100/60 mm Hg. A chest lowing organisms most likely caused the infection?
radiograph shows cardiomegaly and mild pulmonary edema. A Coxsackievirus A
An echocardiogram shows severe left ventricular hypertrophy B Mycobacterium kansasii
and a prominent interventricular septum. The right ventricle C Viridans streptococci
is slightly thickened. During systole, the anterior leaflet of the D Staphylococcus aureus
mitral valve moves into the outflow tract of the left ventricle. E Toxoplasma gondii
The ejection fraction is abnormally high, and the ventricular F Trypanosoma cruzi
volume and cardiac output are both low. Which of the follow-   
ing is the most likely cause of the cardiac abnormalities in this
patient? 56 A 68-year-old man has become increasingly lethargic
A Autoimmunity against myocardial fibers and weak for the past 7 months. On physical examination,
B β-Myosin heavy chain gene mutation his temperature is 36.9° C, pulse is 70/min, respirations are
C Deposition of amyloid fibrils 15/min, and blood pressure is 160/105 mm Hg. On ausculta-
D Excessive iron accumulation tion of his chest, a friction rub is audible. There are no other
E Latent enterovirus infection remarkable findings. The representative gross appearance of
53 A 17-year-old girl jumps up for a block in the third the heart is shown in the figure. Which of the following labo-
match of a volleyball tournament and suddenly collapses. ratory findings is most likely to be reported for this patient?
She requires cardiopulmonary resuscitation. A similar epi- A Elevated serum anti–streptolysin O titer
sode occurs a month later. She had been healthy all her life B Elevated plasma renin level
and complained only of limited episodes of chest pain in C Increased blood urea nitrogen level
games during the current school year. Which of the following D Increased serum CK-MB level
pathologic findings of the heart is most likely to be present in E Positive ANA with “rim” pattern
this girl? F Positive viral serology
A Extensive myocardial hemosiderin deposition
B Haphazardly arranged hypertrophied septal

myocytes
C Large, friable vegetations with destruction of aortic

valve cusps
D Mitral valvular stenosis with left atrial enlargement
E Tachyzoites within foci of myocardial necrosis and

inflammation
54 An 86-year-old man has had increasing dyspnea and
reduced exercise tolerance for the past 7 years. On physical
examination, he is afebrile and has a blood pressure of 135/85
mm Hg. An irregularly irregular heart rate averaging 76/min
is audible on auscultation of the chest. Crackles are heard at
the bases of the lungs. A chest radiograph shows mild car-
diomegaly and mild pulmonary edema. Echocardiography
shows slight right and left ventricular wall thickening with
reduced left and right ventricular wall motion, reduced left
ventricular filling, and an ejection fraction estimated to be
25%. An endomyocardial biopsy specimen shows amor-
phous pink-staining deposits between myocardial fibers, but
no inflammation and no necrosis. Echocardiography would

C H A P T E R 1 2   The Heart 173

57 A 52-year-old woman has had a chronic cough for the 59 A 73-year-old woman has had episodes of chest pain
past 2 years, accompanied by a small amount of occasionally during the past week. She is afebrile. Her pulse is 80/min, res-
blood-streaked, whitish sputum. On physical examination, her pirations are 16/min, and blood pressure is 110/70 mm Hg.
temperature is 37.9° C, pulse is 72/min, respirations are 22/min, On auscultation of the chest, heart sounds seem distant, but
and blood pressure is 125/80 mm Hg. Crackles are heard on the lung fields are clear. Neck veins are distended to the angle
auscultation over the upper lung fields. Heart sounds are faint, of the jaw, even while sitting. There is a darkly pigmented,
and there is a 15 mm Hg inspiratory decline in systolic arterial irregular, 1.2-cm skin lesion on the right shoulder. A chest ra-
pressure. The chest radiograph shows prominent heart borders diograph shows prominent borders on the left and right sides
with a “water bottle” configuration. Pericardiocentesis yields of the heart. Pericardiocentesis yields bloody fluid. Labora-
200 mL of bloody fluid. Infection with which of the following tory findings include a serum troponin I level of 0.3 ng/mL.
organisms is most likely to produce these findings? Which of the following lesions is the most likely cause of these
A Candida albicans findings?
B Coxsackievirus B A Calcific aortic stenosis
C Group A streptococcus B Coronary atherosclerosis
D Mycobacterium tuberculosis C Epicardial metastases
E Staphylococcus aureus D Mitral valvulitis
   E Tuberculous pericarditis

58 A 31-year-old man experienced chest pain, became in- 60 A 48-year-old, previously healthy woman reports having
creasingly dyspneic and nauseated, and lost consciousness suddenly lost consciousness four times in the past 6 months.
multiple times. Seven days after the appearance of these In three instances, she was unconsciousness for only a few
symptoms, he was found dead in his sleep. External examina- minutes. After the fourth episode 1 month ago, she was uncon-
tion of the body by the medical examiner shows no evidence scious for 6 hours and had weakness in her right arm and dif-
of trauma. The body is 166 cm (5 ft 5 in) in height and weighs ficulty speaking. On physical examination, she is afebrile, and
75 kg (BMI 27). The gross appearance of the chest cavity at her blood pressure is normal. No murmurs are auscultated. She
autopsy with the pericardial sac opened is shown in the figure. has good carotid pulses with no bruits. Which of the following
What is the most likely underlying cause of his death? cardiac lesions is most likely to be present in this woman?
A Coronary atherosclerosis A Bicuspid aortic valve
B Dilated cardiomyopathy B Coronary artery thrombosis
C Disseminated tuberculosis C Left atrial myxoma
D Systemic sclerosis D Mitral valve stenosis
E Malignant melanoma E Pericardial effusion
F Marfan syndrome
G Takayasu arteritis 61 A 55-year-old man undergoes orthotopic cardiac trans-
plantation. Two months later, an endomyocardial biopsy
specimen shows focal myocardial cell death with scattered
perivascular lymphocytes and plasma cells. He is treated with
sirolimus. Which of the following pathologic processes best
accounts for these biopsy findings?
A Autoimmunity
B Autophagy
C Ischemia
D Infection
E Rejection

62 A 45-year-old man receives a cardiac allograft for dilated
cardiomyopathy. He has no problems with rejection, but 5 years
later he has worsening exercise tolerance with increasing dys-
pnea and peripheral edema. Echocardiography shows a reduced
ejection fraction of 35%. Which of the following pathologic
abnormalities has he most likely developed in the allograft?
A Amyloidosis
B Constrictive pericarditis
C Coronary arteriopathy
D Non-Hodgkin lymphoma
E Toxoplasmosis

1 7 4 U N I T I I   Diseases of Organ Systems

ANSWERS 5   E  Paroxysmal nocturnal dyspnea is a feature of left-
sided congestive heart failure, and rheumatic heart dis-
1  F  The pacemaker for the heart is the sinoatrial (SA) ease most often involves the mitral, aortic, or both valves,
node, with a natural rhythm near 70/min and a normal and left-sided valvular disease leads to pulmonary edema.
range of 60/min to 100/min. Other parts of the cardiac While upright, pulmonary edema fluid is more concentrat-
conduction system pass along this rate. Rates less than ed at lung bases, which helps improve breathing. Rheumat-
60/min are defined as bradycardia, and rates greater than ic heart disease was more common before antibiotic ther-
100/min are defined as tachycardia. Bradyarrhythmias apy for group A β-hemolytic streptococcal infections was
less than 50/min suggest an SA node disorder. SA node available, and multiple bouts beginning in childhood led to
dysfunction may worsen with cardioactive drugs, such as valvular damage over decades. An atrial myxoma usually
cardiac glycosides, β-adrenergic blockers, calcium chan- occurs on the left side of the heart, but the obstruction is
nel blockers, and amiodarone. An increase in sinus rate often intermittent. Fibrinous pericarditis can produce chest
results from an increase in sympathetic tone acting via pain, but the amount of accompanying fluid is often small
β-adrenergic receptors or a decrease in parasympathetic so that cardiac function is not impaired. Giant cell myocar-
tone acting via muscarinic receptors, or both. Abnormali- ditis is a rare cause of cardiac failure. Libman-Sacks endo-
ties involving the other listed options are unlikely to pro- carditis, seen in systemic lupus erythematosus, typically
duce such a pronounced and consistent bradycardia. does not impair valvular or ventricular function.

PBD9 524–525  BP9 365–367  PBD8 531 PBD9 529  BP9 367, 387  PBD8 535–536  BP8 381

2  F  Native cardiac stem cells can proliferate and replace 6  B  The findings point to pure right-sided congestive
cardiac myocytes throughout life, but these stem cells are heart failure. Rarely, this can be caused by right-sided car-
most active in neonates. They have the potential to respond diac valvular lesions, such as tricuspid or pulmonic steno-
to injury. Some ventricular septal defects do close during life. sis. Pulmonary hypertension resulting from obstructive
Research is ongoing regarding methods for inducing stem cell lung diseases, such as emphysema or chronic bronchitis,
proliferation. Of the remaining cells listed, adipocytes enlarge most often caused from smoking cigarettes, is much more
with aging. Endothelial cells may proliferate to produce more common. Primary pulmonary hypertension also can cause
coronary collateral channels in response to exercise training, right-sided heart failure, but it is a much less common cause
and they can resurface vascular grafts. Fibroblasts respond to than obstructive lung diseases. Because acute myocardial
injury by producing collagenous scar tissue that reduces infarction usually affects the left ventricle, left-sided heart
contractility. failure would be more common in these patients. Chronic
left-sided heart failure eventually can lead to right-sided
PBD9 525  PBD8 537 heart failure.

3   E  These findings are consistent with right-sided conges- PBD9 530  BP9 368, 388  PBD8 536–537  BP8 381–382
tive heart failure leading to peripheral edema, body cavity
effusions (pleural effusions in this case), passive congestion 7   D  There are a number of mutations in genes linked to
of the liver, and jugular venous distension. Pure right-sid- congenital heart disease that encode proteins in transcrip-
ed failure is less common than left-sided failure, and the tion or signaling pathways. The NOTCH pathway plays a
former most often follows pulmonary disease (cor pulmo- role in modulation of vascular development, including car-
nale). Chronic obstructive pulmonary disease (COPD) is diac outflow tracts. NOTCH2 mutations are associated with
more common than restrictive lung disease, and smoking tetralogy of Fallot, as in this infant. β-MHC gene mutations are
leads to COPD. Atrial myxomas are uncommon, more often associated with some cases of hypertrophic cardiomyopathy.
on the left side of the heart, and may produce intermittent Fibrillin-1 (FBN1) gene mutations underlie Marfan syndrome.
valvular obstruction. Essential hypertension is systemic KCNQ1 mutations may be seen with long QT syndrome. One
and places a pressure load on the left side of the heart. form of cardiac amyloidosis is linked to transthyretin (TTR)
Hyperlipidemia is a risk factor for ischemic heart disease gene mutations.
that is more likely to involve the left side of the heart. Rheu-
matic heart disease may produce heart failure, but it is PBD9 532–533  BP9 369  PBD8 538–539
more often left-sided.
8  E  This shunt results from abnormal confluence of pul-
PBD9 526–527, 530  BP9 365  PBD8 545, 558  BP8 388, 390 monary veins leading to the right atrium (or systemic veins),
and not the left. Obstruction is often present, as in this case,
4  C  Left-sided congestive heart failure leads to pulmonary with pulmonary congestion. Deoxygenated systemic and
congestion and edema. Systemic hypertension is common oxygenated pulmonary venous blood mix in the right atrium.
and leads to pressure load with predominantly concentric left There must be an atrial septal defect for blood to reach the
ventricular hypertrophy with systolic dysfunction. The other left atrium, but an ASD by itself does not explain this case.
listed options are more likely to produce diastolic dysfunction A coarctation is not associated with cyanosis; a preductal
and decrease of both right and left ventricular function. coarctation is life-threatening. Patent ductus arteriosus is a

PBD9 527–529  BP9 366–367  PBD8 545, 558  BP8 388, 390

C H A P T E R 1 2   The Heart 175

left-to-right shunt without cyanosis. Tetralogy of Fallot can produce a loud murmur because of the minimal pressure
lead to cyanosis, but mixing of blood occurs at an overriding differential between the atria. Because pulmonic stenosis is a
aorta. component of tetralogy of Fallot, no pulmonary hypertension
results, and the right-to-left shunting can lead to cyanosis with
PBD9 531–533  BP9 369  PBD8 543  BP8 384 decreased arterial oxygen saturation. Total anomalous pul-
monary venous return is not accompanied by a murmur be-
9   D  This is the infamous “paradoxical embolus” that has cause of the low venous pressure.
appeared far more often in question sets than in real life.
She started with thrombophlebitis that led to pulmonary PBD9 535  BP9 371–372  PBD8 541–542  BP8 385
embolism, but there must be an explanation for the “stroke”
that then occurred. Pulmonary emboli can obstruct the pul- 1 3  E  Cyanosis at this early age suggests a right-to-left
monary arterial circulation, raising right atrial pressure, shunt. Truncus arteriosus, transposition of the great arter-
and opening a patent foramen ovale that normally remains ies, and tetralogy of Fallot are the most common causes of
closed because of higher left atrial pressure. The remaining cyanotic congenital heart disease. The cerebral lesion sug-
choices do not explain pulmonary thromboembolism. A left gests an abscess as a consequence of septic embolization
atrial myxoma can embolize to the brain; lesions of endocar- from infective endocarditis, which can complicate congeni-
ditis are most often on the left side of the heart and could tal heart disease. Atrial septal defect, patent ductus arterio-
produce cerebral emboli; a ventricular aneurysm is virtually sus, and ventricular septal defect initially lead to left-to-right
always on the left side of the heart because it results from a shunts, though the shunt may reverse with development of
healed infarction, and can be filled with mural thrombus that pulmonary hypertension. Coarctation is not accompanied
can embolize. by a shunt and cyanosis. In most cases, a bicuspid valve is
asymptomatic until adulthood, and there is no shunt.
PBD9 533–534  BP9 370–371  PBD8 541  BP8 385
PBD9 535–537  BP9 372–373  PBD8 542–544  BP8 383
10  D  The figure shows a large ventricular septal defect.
By the age of 5 years, such an uncorrected defect causes 14  A  In tetralogy of Fallot, the severity of the obstruction
marked shunting of blood from left to right, causing pul- to the right ventricular outflow determines the direction of
monary hypertension (Eisenmenger complex). The left and flow. If the pulmonic stenosis is mild, the abnormality re-
right ventricular chambers undergo hypertrophy and some sembles a ventricular septal defect, and the shunt may be
dilation, but the functioning of the cardiac valves is not from left to right with no cyanosis. With significant pulmo-
greatly affected. In most cases, congenital heart disease is nary outflow obstruction, the right ventricular pressure may
not an antecedent to ischemic heart disease. Nonbacterial reach or exceed systemic vascular resistance, and the blood
thrombotic endocarditis most often occurs secondary to a would be shunted from right to left, producing cyanotic
hypercoagulable state in adults. Restrictive cardiomyopathy heart disease. Even if pulmonic stenosis is mild at birth, the
may occur from conditions such as amyloidosis or hemo- pulmonary orifice does not expand proportionately as the
chromatosis. heart grows, and cyanotic heart disease supervenes.

PBD9 535  BP9 370–371  PBD8 541  BP8 384–385 PBD9 535–536  BP9 372–373  PBD8 543  BP8 385–386

1 1  B  A persistent ostium secundum is the most common 15  D  The figure shows that the aorta emerges from the
form of atrial septal defect. Because atrial pressures are low, right ventricle, and the pulmonic trunk exits the left ventri-
the amount of shunting from the left atrium to the right atrium cle, consistent with complete transposition of the great ves-
is small, and this lesion may remain asymptomatic for many sels. Unless there is another anomalous connection between
years. Eventually, pulmonary hypertension can occur, with the pulmonary and systemic circulations, this condition is
reversal of the shunt. Cyanosis is a feature of a right-to-left incompatible with extrauterine life. The most common ad-
shunt. A dilated heart with enlarged atria predisposes to mu- ditional anomalous connections would be ventricular septal
ral thrombosis and embolism. Pericardial effusions may occur defect, patent ductus arteriosus, and patent foramen ovale
much later, if congestive heart failure develops. (or atrial septal defect). In pulmonic and aortic stenosis, the
great arteries are normally positioned, but small. In tetralogy
PBD9 534  BP9 370–371  PBD8 541   BP8 383–384 of Fallot, the aorta overrides a ventricular septal defect, but is
not transposed. In truncus arteriosus, the spiral septum that
12  D  Although often not causing a large shunt defect, a embryologically separates the great arteries does not develop
patent ductus arteriosus can produce a significant murmur properly.
and predispose to infection. This left-to-right shunt may
eventually result in pulmonary hypertension. An atretic PBD9 536–537  BP9 372–373  PBD8 543  BP8 386–387
valve has no flow across it and does not produce a murmur,
but there would be a murmur across a shunt around the 1 6  B  In children and adults, the coarctation is typically
atretic valve. Aortic atresia is not compatible with continued postductal, and collateral branches from the proximal aorta
survival, as seen in hypoplastic left heart syndrome. Aortic supply the lower extremities, leading to the large pulse dif-
coarctations by themselves produce no shunting and no pul- ferential between upper and lower extremities. Collaterals of-
monary hypertension. An atrial septal defect is unlikely to ten involve intercostal arteries whose enlargement produces

1 7 6 U N I T I I   Diseases of Organ Systems

“rib notching” on chest radiographs. Diminished renal blood of any atheromas, but can develop hypercoagulable states.
flow below the coarctation increases renin production and When this occurs, there is widespread thrombosis in normal
promotes hypertension. Aortic valve stenosis causes left-sided blood vessels. Individuals with chronic alcoholism often have
heart failure and no pressure differential in the extremities. A less atherosclerosis than individuals of the same age who do
patent ductus arteriosus produces a small left-to-right shunt. not consume large amounts of alcohol. The cystic medial ne-
Transposition results in a right-to-left shunt with cyanosis. crosis that occurs in Marfan syndrome most often involves
Tricuspid valve atresia affects the right side of the heart. the ascending aorta and predisposes to dissection that could
involve coronary arteries, although with external compres-
PBD9 537  BP9 373–374  PBD8 544  BP8 387–388 sion. Polyarteritis nodosa can involve coronary arteries and
give rise to coronary thrombosis when the arterial wall is ne-
17  C  These findings are compatible with hypoplastic left crotic and inflamed.
heart syndrome, which may have varying degrees of sever-
ity, ranging from severe (as in this case, with virtually no PBD9 540–543  BP9 374–376  PBD8 547–549  BP8 389–390
function on the left side of the heart) to milder degrees of
hypoplasia. Most of the oxygenated blood returning to the 20  B  Angina pectoris typically occurs when coronary artery
left atrium is shunted across the foramen ovale back to the narrowing exceeds 75%. His risk factors include hyperglyce-
lungs, increasing pulmonary flow and decreasing oxygen- mia (diabetes mellitus) and hypercholesterolemia. Calcific aor-
ation. Less oxygenated blood exiting the right ventricle into tic stenosis leads to left-sided congestive heart failure (CHF),
the pulmonic trunk can shunt through a patent ductus arte- and the extra workload of the left ventricle may cause angina
riosus to the aorta to supply the systemic circulation. Anom- pectoris. Calcific aortic stenosis (in the absence of a congenital
alous venous return does not generally connect to the aorta, bicuspid aortic valve) is rarely symptomatic at 50 years of age,
and there still must be a connection from the lungs to the however. Cardiomyopathies result in heart failure, but with-
aorta. The right fourth aortic arch rarely persists. Truncus out chest pain. Patients with rheumatic heart disease are affect-
arteriosus is an anomalous, incomplete separation of the pul- ed by slowly worsening CHF. Pericarditis can produce chest
monic and aortic trunks. If there is virtually no left ventricu- pain, although not in relation to exercise, and it is not relieved
lar chamber, a ventricular septal defect would not provide by nitroglycerin. Viral myocarditis may last for weeks, but not
any significant flow. for 1 year, and pain may be present at rest.

PBD9 531, 538  BP9 369  PBD8 544 PBD9 539–540  BP9 376  PBD8 545, 558  BP8 388, 390

1 8  A  Marked coronary artery occlusion with this degree of 21  E  Myocardial infarction results from occlusion of large
stenosis prevents adequate perfusion of the heart when myo- coronary arterial branches, and in most cases an occluding
cardial demand is increased during exertion. He has angina thrombus is present. The posterior left ventricle and septum
on exertion and recently developed unstable angina, which are supplied by the posterior descending artery. The left
is manifested by increased frequency and severity of the at- circumflex artery supplies the lateral left ventricular wall,
tacks and angina at rest. The ST segment elevation suggests whereas the left anterior descending artery supplies the ante-
a developing acute coronary syndrome with myocardial rior left ventricle. An aortic dissection that extends proximally
ischemia, but the lack of cardiac enzyme elevation suggests may cause tamponade, compressing the heart, great vessels,
infarction has not yet occurred. In most patients, unstable an- and even coronary arteries, but this is much less likely a cause
gina is induced by disruption of an atherosclerotic plaque fol- for myocardial infarction than atherosclerotic coronary arte-
lowed by a mural thrombus and possibly distal embolization, rial disease. The coronary sinus is where venous blood from
vasospasm, or both. An acute myocardial infarction (MI) can the myocardium drains into the right atrium.
lead to focal fibrinous pericarditis, but it is unlikely to lead to
extensive scarring that surrounds the heart. Fibrosis is a late PBD9 540–543  BP9 379  PBD8 547–549  BP8 388–390
finding from healing of infarction. Hypertrophy of the heart
is unlikely to progress significantly in this case because there 2 2  C  The figure shows intensely eosinophilic myocardial
is neither hypertension nor a valvular lesion. Mural throm- fibers with loss of nuclei, all are indicative of coagulative
bosis may develop on the endocardial surface overlying an necrosis. The deeply red-stained transverse bands are called
infarction, and may fill a ventricular aneurysm following an contraction bands. Neutrophils infiltrate between myocardial
MI. An acute MI may be complicated by papillary muscle fibers. This pattern is most likely caused by a myocardial in-
rupture with mitral valve insufficiency. farction (MI) that is approximately 24 to 48 hours old. Chest
pain is present in most but not all cases of MI. Rheumatic
PBD9 538–540  BP9 374–376  PBD8 546, 558  BP8 388–390 myocarditis is characterized by minimal myocardial necrosis
with foci of granulomatous inflammation (Aschoff bodies).
19  C  The figure shows a coronary artery with marked lumi- There is no significant inflammation with restrictive cardio-
nal narrowing caused by atheromatous plaque, complicated myopathies such as amyloidosis or hemochromatosis. Septic
by a recent thrombus filling the narrowed lumen. Atheroscle- emboli result in focal abscess formation. In viral myocarditis,
rosis is accelerated with diabetes mellitus. When a premeno- there is minimal focal myocardial necrosis with round cell
pausal woman develops severe atherosclerosis, as in this infiltrates.
case, underlying diabetes mellitus or a lipid disorder must be
strongly suspected. Patients with leukemias may have ­reversal PBD9 544–546  BP9 379–381  PBD8 553–554  BP8 391–395

C H A P T E R 1 2   The Heart 177

2 3  E  Reperfusion of an ischemic myocardium by sponta- 2 6  C  The laboratory findings suggest an acute myocardial
neous or therapeutic thrombolysis changes the morphologic infarction. Individuals with familial hypercholesterolemia
features of the affected area. Reflow of blood into vasculature have accelerated and advanced atherosclerosis, even by the
injured during the period of ischemia leads to mitochondrial second or third decade. DiGeorge syndrome can be associ-
dysfunction, followed by leakage of blood into the tissues ated with various congenital heart defects, but survival with
(hemorrhage). Contraction bands are composed of closely this syndrome is usually limited by infections resulting from
packed hypercontracted sarcomeres. They are most likely pro- cell-mediated immunodeficiency. Down syndrome (trisomy 21)
duced by exaggerated contraction of previously injured myo- is often accompanied by endocardial cushion defects, not
fibrils that are exposed to a high concentration of calcium ions ischemic heart disease. Hereditary hemochromatosis may
from the plasma. The damaged cell membrane of the injured result in an infiltrative cardiomyopathy with iron overload,
myocardial fibers allows calcium to penetrate the cells rap- more typically by the fifth decade. Marfan syndrome may
idly. Free radical formation and release of leukocyte enzymes result in aortic dissection or floppy mitral valve.
further potentiate myocardial cell death. Hemorrhage would
not be a prominent feature in the other listed options. Vascu- PBD9 547–548  BP9 382–383  PBD8 545–547  BP8 388–393
litides involving the heart are uncommon; Takayasu arteritis 2 7  F  The figure shows an enlarged and dilated heart with a
can involve coronary arteries, but is most often a rare pediat- large ventricular aneurysm with a thin wall and white fibrous
ric condition. Drugs used to control arrhythmias during acute endocardial surface. Such an aneurysm most likely results
coronary syndromes are unlikely to have hemorrhage as an from weakening of the ventricular wall at the site of a prior
adverse event. Angioplasty per se does not increase the risk healed myocardial infarction. Because of the damage to the
for hemorrhage, and stents help to keep the artery open lon- endocardial lining, with stasis and turbulence of blood flow
ger. Septic embolization from infected valvular vegetations to in the region of the aneurysm, mural thrombi are likely to
a coronary artery is uncommon, although such emboli may develop. When detached, thrombi in the left side of the heart
produce focal necrosis and hemorrhage. embolize to the systemic circulation and can cause infarcts
elsewhere. An atrial myxoma is the most common primary
PBD9 545–547  BP9 381–382  PBD8 553–555  BP8 394–395 cardiac neoplasm, but it is rare and is not related to ischemic
heart disease. Cardiac rupture with tamponade is most like-
24  B  CK activity begins to increase 2 to 4 hours after an MI, ly to occur 5 to 7 days after an acute myocardial infarction.
peaks at about 24 to 48 hours, and returns to normal within 72 Constrictive pericarditis follows a previous suppurative or
hours. Troponin I levels begin to increase at about the same tuberculous pericarditis. Hypertrophic cardiomyopathy is not
time as CK and CK-MB, but remain elevated for 7 to 10 days. related to ischemic heart disease, but 50% of cases are familial
Total CK activity is a sensitive marker for myocardial injury and may be related to genetic mutations in genes encoding
in the first 24 to 48 hours. CK-MB offers more specificity, but for cardiac contractile elements. Infective endocarditis is more
not more sensitivity. The risk for myocardial rupture is great- likely to complicate valvular heart disease or septal defects.
est from 4 to 7 days after transmural myocardial necrosis. PBD9 549  BP9 383–384  PBD8 556–557  BP8 396–397
This patient had an MI on the day of the shoulder pain. When
he saw the physician on day 3, the CK levels had returned 2 8  A  The history of diabetes mellitus and the chest pain
to normal, but troponin I levels remained elevated. Three put ischemic heart disease at the top of the differential diag-
days later, the infarct ruptured, and blood filled the pericar- nosis list for this man, who has findings with both right and
dial cavity. Cardiac valves are essentially avascular and not left ventricular failure and enlargement, suggesting isch-
subject to ischemic injury. Ventricular aneurysm formation is emic cardiomyopathy. An elevated serum B-type natriuretic
a late complication of a healed MI. Papillary muscles are at peptide (which is measured instead of atrial natriuretic
risk for rupture, just like the free wall, but the consequence peptide) is consistent with heart failure. Occlusive coro-
would be acute valvular insufficiency, not hemopericardium. nary atherosclerosis may lead to multiple infarctions, or may
A transmural MI may lead to pericarditis, often with some silently cause progressive myofiber loss, but the end stage
accompanying pericardial effusion, but the acute event here is ischemic cardiomyopathy. Atrial mural thrombus formation
in the time frame described suggests rupture. can occur with aortic valve dysfunction and with dysrrhyth-
mias. Myofiber disarray is characteristic for hypertrophic
PBD9 547–548  BP9 382–383  PBD8 555  BP8 395 cardiomyopathy, which affects the interventricular septum
preferentially and is usually symptomatic by young adult-
25  C  Of the enzymes listed, CK-MB is the most specific hood. Although rheumatic valvulitis with thickening may
for myocardial injury from the acute myocardial infarction involve both the left and right sides of the heart, this is un-
(MI) described in this patient. The levels of this enzyme usual, and it is not associated with coronary artery disease.
begin to increase within 2 to 4 hours of ischemic myocardial Pericardial fluid collection may constrict heart motion, with-
injury. ALT elevation is more specific for liver injury. AST is out an enlarged heart, and hemopericardium may acutely
found in various tissues; elevated levels are not specific for occur with ventricular rupture.
myocardial injury. The elevation of lactate dehydrogenase
(LDH)-1 compared with LDH-2 suggests myocardial injury, PBD9 550  BP9 384–385  PBD8 558  BP8 397
but LDH activity peaks 3 days after an MI. C-reactive protein
is elevated with inflammatory processes, but is nonspecific; 2 9  F  An ischemic cardiomyopathy can result from coro-
it has been used as a predictor of acute coronary syndromes. nary atherosclerosis, but she does not have an acute coronary
Lipase is a marker for pancreatitis. syndrome. The major identifiable risk factor in this case is

PBD9 547–548  BP9 382–383  PBD8 555  BP8 390–396

1 7 8 U N I T I I   Diseases of Organ Systems

hypercholesterolemia, and the HMG-CoA reductase inhibi- ventricular hypertrophy, and left-sided heart failure with
tors (the statin drugs) are helpful to lower cholesterol, specifi- pulmonary edema. In individuals with congenitally bicus-
cally LDL cholesterol. Amiodarone is used to treat intractable pid valves, symptoms often appear by 50 to 60 years of age.
arrhythmias. Glyburide is used in the treatment of type 2 By contrast, calcific aortic stenosis of tricuspid valves mani-
diabetes mellitus, but this patient is not hyperglycemic. Nitro- fests in the seventh or eighth decade. Ischemic heart disease,
glycerin is a vasodilator used to treat angina. Propranolol is a expected with diabetes mellitus, does not lead to valvular
β-blocker that has been used to treat hypertension, and it may stenosis. In infective endocarditis, the patient would have
exacerbate bradycardia and congestive heart failure. Alteplase an infection, and the valve would tend to be destroyed,
(tissue plasminogen activator) is used early in treatment of leading to insufficiency. In Marfan syndrome, loss of elastic
coronary thrombosis to help reestablish coronary blood flow. tissue in the media leads to aortic root dilation, producing
aortic valvular insufficiency. Systemic hypertension accounts
PBD9 550  BP9 384–385  PBD8 558  BP8 397 for left ventricular hypertrophy, but the aortic valve is not
affected.
3 0  D  In the period immediately after coronary thrombosis,
arrhythmias are the most important complication and can lead PBD9 554–556  BP9 389  PBD8 562–563  BP8 401–402
to sudden cardiac death. It is believed that, even before isch-
emic injury manifests in the heart, there is greatly increased 3 4  D  Mitral annular calcification is often an incidental find-
electrical irritability predisposing to dysrhythmias. Myocardial ing on chest radiograph, echocardiography, or at autopsy.
rupture, valvular insufficiency from papillary muscle involve- Larger accumulations of calcium in the mitral ring can impinge
ment, and pericarditis occur several days later. Another com- on the conduction system, however, causing arrhythmias or
plication is a left ventricular aneurysm, a late complication of disrupting the endocardium to provide a focus for infective
the healing of a large transmural infarction; a mural thrombus endocarditis and thrombus formation (which can embolize
may fill an aneurysm and become a source of emboli. If por- and cause a stroke, as in this patient). Some cases are associated
tions of the coronary thrombus break off and embolize, they with mitral valve prolapse. Carcinoid heart disease leads to
enter smaller arterial branches in the distribution already af- endocardial and valvular collagenous thickening. Hyperpara-
fected by ischemia. Valvular insufficiency from a ruptured thyroidism can cause metastatic calcification, which usually
papillary muscle would occur later in the course. does not involve the heart, and deposits would not be so focal;
this patient does not have hypercalcemia. Infective endocarditis
PBD9 550–551  BP9 385–386  PBD8 557  BP8 391, 395–396 is a destructive process, and healing may lead to fibrosis, but
not to nodular calcium deposition. The most common infiltra-
3 1  A  The most common cause for sudden cardiac arrest is tive cardiomyopathies are hemochromatosis and amyloidosis.
ischemic heart disease. The risk for sudden death is increased Rheumatic heart disease can lead to scarring with some cal-
with worsening atherosclerotic coronary arterial narrowing. cium deposition, but the valve leaflets undergo extensive scar-
However, the first event with an acute coronary syndrome is ring, with shortening and thickening of the chordae tendineae
typically an arrhythmia, and this is why resuscitation, includ- that preclude upward prolapse. Senile calcific stenosis involves
ing defibrillation, can be successful, and survivors may have no the aortic valve; in this case, there is no evidence of stenosis.
ECG or enzyme changes to suggest myocardial infarction has
occurred. Inflammation with infarction or infection takes days PBD9 556  BP9 389  PBD8 563  BP8 402
to develop. A sudden valvular incompetence from papillary
muscle rupture, or wall rupture, may complicate an infarction 35  A  Note that this valve has three cusps, but the nodular
3 to 7 days following the initial event. deposits of calcium interfere with cusp movement to cause
calcific aortic stenosis. This is a degenerative change that may
PBD9 551–552  BP9 385–386  PBD8 558–559  BP8 397–398 occur in a normal aortic valve with aging. Syncope may occur
upon exertion because the stenotic valve prevents stroke vol-
32  E  The markedly thickened left ventricular wall is ume from increasing in the presence of systemic vasodilation,
characteristic of myocardial fiber hypertrophy caused by resulting in hypotension. Atherosclerosis does not produce val-
increased pressure load from hypertension, which often is vular disease from involvement of the valve itself. Congenital
associated with chronic renal disease. Left ventricular fail- anomalies with chromosomal aneuploidies (e.g., trisomy 21)
ure leads to pulmonary edema. Chronic alcoholism is most are unlikely to be associated with aortic stenosis or a bicus-
often associated with dilated cardiomyopathy. Diabetes pid valve. Hypercalcemia may cause metastatic calcification,
mellitus accelerates atherosclerosis, leading to ischemic but it is unlikely in cardiac valves; it is more likely to cause
heart disease and myocardial infarction; the normal glucose arrhythmias. Systemic lupus erythematosus may give rise
level does not fit with diabetes mellitus. Hemochromatosis to small sterile vegetations on mitral or tricuspid valves, but
leads to dilated cardiomyopathy. Pneumoconioses produce these rarely cause valve disease. In syphilis, the aortic root di-
restrictive lung disease with cor pulmonale and predomi- lates, and aortic insufficiency results.
nantly right ventricular hypertrophy.
PBD9 554–555  BP9 389–390  PBD8 561–563  BP8 401–402
PBD9 552–553  BP9 387  PBD8 559–560  BP8 380
36  D  Myxomatous mitral valve degeneration can be
33  A  The bicuspid valve shown has a tendency to calci- primary from a connective tissue disorder such as Marfan
fy with aging, which eventually can result in stenosis, left syndrome or secondary to chronic hemodynamic forces

C H A P T E R 1 2   The Heart 179

(later in life); the chordae tendineae become elongated and involvement is less likely. In almost all cases, the fibrinous
can rupture to produce acute valvular incompetence. De- pericarditis seen during the acute phase with friction rub re-
structive vegetations occur with infective endocarditis, and solves without significant scarring, and constrictive pericar-
develop over days to weeks. Dystrophic calcification in older ditis does not typically develop. Although there is myocar-
persons can occur in the mitral annulus or aortic valve; the ditis with acute rheumatic fever, it does not lead to dilated
former is typically incidental and the latter may produce cardiomyopathy. A left ventricular aneurysm is a complica-
symptomatic stenosis. Fibrinoid necrosis is most typical of tion of ischemic heart disease. Primary cardiac neoplasms,
hyperplastic arteriolosclerosis, not cardiac valves. Rheumat- including myxoma, are rare and not related to infection.
ic heart disease leads to valvular scarring with shortening
and thickening of the chordae tendineae, not thinning and PBD9 557–559  BP9 391–392  PBD8 565–566  BP8 403–406
elongation.
40  A  Acute rheumatic fever can involve any or all lay-
PBD9 556–557  BP9 390  PBD8 563–564  BP8 402–403 ers of the heart. Because rheumatic fever follows group A
streptococcal infections, the antihyaluronidase, anti-DNase,
3 7  B  A floppy (prolapsed) mitral valve is usually asymp- and anti–streptolysin O (ASO) titers are often elevated. The
tomatic. When symptomatic, it can cause fatigue, chest pain, strains of group A streptococci that lead to acute rheumatic
and arrhythmias. Some cases are linked to clinical depres- fever are less likely to cause glomerulonephritis, so an ele-
sion and anxiety, and others are associated with Marfan vated creatinine level is unlikely. The ANA level could be el-
syndrome. Valvular vegetations suggest endocarditis, and evated in systemic lupus erythematosus, which is most likely
a murmur is likely to be heard with infective endocarditis to produce a serous pericarditis. A positive rapid plasma re-
causing valvular insufficiency. A patent ductus arteriosus agin test suggests syphilis, but the clinical features here are
causes a shrill systolic murmur. Pulmonic stenosis is most not those of syphilis, and cardiovascular syphilis is one form
often a congenital heart disease. Tricuspid regurgitation is of tertiary syphilis that develops decades after initial infec-
accompanied by a rumbling systolic murmur. tion. Cardiac troponins are markers for ischemic myocardial
injury. Although their levels may be elevated because of the
PBD9 556–557  BP9 390–391  PBD8 563–564  BP8 402–403 acute myocarditis that occurs in rheumatic fever, this change
is not a characteristic of rheumatic heart disease.
3 8  D  This boy developed acute left ventricular failure, an
uncommon but serious complication of acute rheumatic fever. PBD9 557–559  BP9 391–392  PBD8 565–566  BP8 403–405
Pancarditis with pericarditis, endocarditis, and myocarditis
develop during the acute phase. Myocarditis led to dilation 41  E  The aortic valve shown has large, destructive vegeta-
of the ventricle so severe that the mitral valve became incom- tions. The probe passes through a perforated leaflet, typical
petent. Rheumatic heart disease is now uncommon, and the of infective endocarditis caused by highly virulent organisms
number of children that require prophylactic antibiotic thera- such as Staphylococcus aureus. The verrucous vegetations of
py to prevent just one case is >10,000. Chronic inflammatory acute rheumatic fever are small and nondestructive, and
conditions may produce reactive systemic amyloidosis, but the diagnosis is suggested by an elevated anti–streptolysin
this is unlikely to occur given the limited and episodic nature O titer. A positive ANCA determination suggests a vasculitis,
of the streptococcal infection that causes rheumatic heart dis- which is unlikely to involve cardiac valves. An elevated cre-
ease. Fibrinous pericarditis can produce an audible friction atine kinase–MB level suggests myocardial, not endocardial,
rub, but it is not constrictive, and the amount of fluid and injury. A positive double-stranded DNA finding suggests
fibrin are not great, so no tamponade occurs. Myocardial necro- systemic lupus erythematosus, which can produce nonde-
sis associated with myocarditis is patchy, and the ventricle structive Libman-Sacks endocarditis.
does not rupture to produce tamponade. Fibrosis and fusion
of the mitral valve leaflets develop over weeks to months and PBD9 559–561  BP9 393–394  PBD8 567–568  BP8 406–407
indicate chronic rheumatic valvulitis. Verrucous vegetations
are small and may produce a murmur, but they do not inter- 42  E  Infective endocarditis is present in this man. If there is
fere greatly with valve function and do not tend to embolize. a known cardiovascular congenital anomaly, then dental pro-
cedures may be preceded by prophylactic antibiotic therapy.
PBD9 557–559  BP9 391–392  PBD8 566  BP8 403–406 The systolic murmur suggests a left-sided lesion, with left-to-
right shunt. A small ventricular septal defect (VSD) may not
39  E  The mitral valve in the figure shows shortening and lead to significant shunting of blood and remain subclinical,
thickening of the chordae tendineae typical of chronic rheu- but it still represents a risk for endocarditis. Only a murmur
matic valvulitis, and the small verrucous vegetations (arrow- may provide a clue, and the higher pitch goes with a small-
heads) are characteristic of superimposed acute rheumatic er defect. Most VSDs occur in the membranous septum, but
fever. Valvular scarring can follow years after initial group about 10% are in the muscular septum, and this difference may
A streptococcal infection. Rheumatic heart disease develops be due to closure of many muscular defects during life. The re-
after the immune response directed against the bacterial anti- maining listed options represent less common sites for anoma-
gens (similar to cardiac antigens, and thus a form of molecular lies or areas where infectious endocarditis could develop.
mimicry) damages the heart because streptococcal antigens
cross-react with the heart. The mitral and aortic valves are most PBD9 559–561  BP9 393–394  PBD8 545, 558  BP8 388, 390
commonly affected, so right ventricular dilation from tricuspid

1 8 0 U N I T I I   Diseases of Organ Systems

4 3  A  She developed bacterial septicemia followed by in- persons with malignancies likely have no or minimal isch-
fective endocarditis of the mitral valve. Thus she has a high emic heart disease.
risk for developing complications of infective endocardi-
tis. Such valvular vegetations are destructive of the valve. PBD9 561–562  BP9 394–395  PBD8 568–569  BP8 407–408
The impaired functioning of the mitral valve (most likely
regurgitation) would give rise to left atrial dilation and left 4 6  D  Libman-Sacks endocarditis is an uncommon com-
ventricular failure with pulmonary edema. Septic emboli plication of systemic lupus erythematosus (SLE) that has
from the mitral valve vegetation could reach the systemic minimal clinical significance because the small vegetations,
circulation and give rise to abscesses. Infection of an arterial although they spread over valves and endocardium, are
wall can weaken the wall, resulting in aneurysm formation unlikely to embolize or cause functional flow problems. Calcific
and the potential for rupture. Dilated cardiomyopathy aortic stenosis may be seen in older individuals with tricus-
may be due to chronic alcoholism, or it may be idiopathic. pid valves, or it may be a complication of bicuspid valves.
It may be familial, or it may follow myocarditis, but it is Although pericardial effusions are common in active SLE,
not a direct complication of infective endocarditis. Myx- along with pleural effusions and ascites from serositis, they
omatous degeneration of the mitral valve results from a are usually serous effusions, and no significant hemorrhage
defect in connective tissue, whether well defined or unknown; or scarring occurs. The vegetations of nonbacterial throm-
the mitral valve leaflets are enlarged, hooded, and redun- botic endocarditis are prone to embolize. Mural thrombi are
dant. Lesions on the right side of the valve can produce most likely to form when cardiac chambers are dilated, or
septic emboli that involve the lungs, but vegetations on there is marked endocardial damage. Rheumatic heart dis-
the left side embolize to the systemic circulation, producing ease is an immunologic disease based on molecular mimic-
lesions in the spleen, kidneys, or brain. Pulmonary ab- ry; serologic tests would be positive for anti–streptolysin O
scesses can occur from right-sided infective endocarditis, (ASO), not ANA.
because septic emboli pour into the pulmonary arterial
circulation. PBD9 562  BP9 395  PBD8 569  BP8 408–409

PBD9 559–561  BP9 393–394  PBD8 567–568  BP8 406–407 47  E  Bioprostheses made from pig valves are subject to
wear and tear. The leaflets may calcify, resulting in stenosis, or
4 4  D  Prolonged fever, heart murmur, mild splenomegaly, they may perforate or tear, leading to insufficiency. Thrombo-
and splinter hemorrhages suggest a diagnosis of infective sis with embolization is unlikely to occur with bioprostheses
endocarditis. The valvular vegetations with infective endo- that are indicated for persons who cannot receive anticoagu-
carditis are friable and can break off and embolize. The time lant therapy; it is an uncommon complication of mechanical
course of weeks suggests a subacute form of bacterial endo- prostheses, lessened by anticoagulant therapy. Hemolysis is
carditis resulting from infection with a less virulent organ- not seen in bioprostheses and is rare in modern mechanical
ism, such as viridans streptococci. Group A streptococci are prostheses. Myocardial infarction from embolization or from
better known as a cause for rheumatic heart disease, with a poorly positioned valve is rare. Paravalvular leaks are rare
noninfectious vegetations. Pseudomonas aeruginosa is more complications of the early postoperative period.
likely to cause an acute form of bacterial endocarditis that
worsens over days, not weeks; this organism is more com- PBD9 563  BP9 395–396  PBD8 570–571  BP8 409
mon as a nosocomial infection or it may occur in injection
drug users. Coxsackievirus B and Trypanosoma cruzi are 48  F  Anticoagulant therapy is necessary for patients with
causes of myocarditis. Tuberculosis involving the heart most mechanical prostheses to prevent potential thrombotic com-
often manifests as pericarditis. plications. If the patient is unable to take anticoagulants, use
of a bioprosthesis (porcine valve) may be considered. Aspirin
PBD9 559–561  BP9 393–394  PBD8 567–568  BP8 406–407 in low doses is used to reduce the risk for acute coronary syn-
dromes. Antibiotic therapy with agents such as ciprofloxacin
45  E  So-called marantic vegetations may occur on any is not indicated, unless the patient has an infection or requires
cardiac valve, but tend to be small and do not damage the prophylactic antibiotic coverage for surgical or dental proce-
valves. They have a tendency to embolize, however. They dures. Cyclosporine or other immunosuppressive agents are
can occur with hypercoagulable states that accompany cer- not indicated because allogeneic tissue was not transplanted
tain malignancies, especially mucin-secreting adenocarcino- (a bioprosthesis also is essentially immunologically inert). Di-
mas. Thrombosis can occur anywhere, but is most common goxin is not indicated because the patient’s cardiac function
in leg veins, predisposing to pulmonary thromboembolism. has improved. A β-blocker such as propranolol is not needed
This paraneoplastic state is known as Trousseau syndrome. in the absence of chronic cardiac failure.
Calcific aortic stenosis occurs at a much older age, usually
in the eighth or ninth decade, and produces obstruction but PBD9 563  BP9 395–396  PBD8 570–571  BP8 409
not embolism. Cardiac metastases are uncommon, and they
tend to involve the epicardium; they do not explain embo- 4 9  C  Congestive heart failure with four-chamber dilation
lism with cerebral infarction in this case. A metastatic tumor is suggestive of dilated cardiomyopathy; implicated in cau-
can encase the heart to produce constriction, but this is rare. sation are genetic factors (in 20% to 50% of cases), myocar-
Mural thromboses occur when cardiac blood flow is altered, ditis, and alcohol abuse. The patient’s fractional excretion of
as occurs in a ventricular aneurysm or dilated atrium, but sodium is less than 1%, consistent with prerenal azotemia.

C H A P T E R 1 2   The Heart 181

Many cases of dilated cardiomyopathy have no known cause. fibers are seen. Arrhythmias can occur. If persons with this
Dilation is more prominent than hypertrophy, although both condition survive to adulthood, chronic heart failure may
are present, and all chambers are involved. Amyloidosis develop. Hemochromatosis gives rise to a cardiomyopathy
produces restrictive cardiomyopathy. Hypercholesterolemia in middle age. Valve destruction with vegetations is seen in
would predispose to atherogenesis with coronary artery nar- infective endocarditis and would be accompanied by signs of
rowing and ischemic heart disease. Rheumatic heart disease sepsis. Rheumatic heart disease with chronic valvular chang-
would most often produce some degree of valvular stenosis, es would be unusual in a patient this age, and the course is
often with some regurgitation, and the course usually is more most often slowly progressive. Tachyzoites of Toxoplasma
prolonged. Chagas disease from T. cruzi infection affects the gondii signify myocarditis, a process that may occur in im-
right ventricle more often than the left. munocompromised individuals.

PBD9 564–565  BP9 396–400  PBD8 572–574  BP8 410–411 PBD9 568–570  BP9 396–400  PBD8 575–576  BP8 412–413

50  C  The findings point to dilated cardiomyopathy (DCM) 5 4  B  Reduced cardiac chamber compliance is a feature of
with both right-sided and left-sided heart failure. The most the restrictive form of cardiomyopathy. Cardiac amyloidosis
common toxin producing DCM is alcohol, and individuals may be limited to the heart (so-called senile cardiac amyloi-
with chronic alcoholism are more likely to have DCM than to dosis derived from transthyretin protein) or may be part of
have ischemic heart disease. Acetaminophen ingestion can be organ involvement in systemic amyloidosis derived from
associated with hepatic necrosis and analgesic nephropathy. serum amyloid-associated (SAA) protein or, in multiple my-
Cocaine can produce ischemic effects on the myocardium. eloma, derived from light chains (AL amyloid). Incidental iso-
Lisinopril is an angiotensin-converting enzyme inhibitor that lated atrial deposits of amyloid are derived from atrial natri-
is used to treat hypertension. Nicotine in cigarette smoke is a uretic peptide. Myocardial fiber dysfunction markedly reduces
risk factor for atherosclerosis. Propranolol is a β-blocker that ventricular compliance. Dynamic left ventricular outflow ob-
has been used to treat hypertension, and it may exacerbate struction is characteristic of hypertrophic cardiomyopathy.
bradycardia and congestive heart failure. Valvular insufficiency of mitral and tricuspid valves can occur
with dilated cardiomyopathy, which also reduces contractility
PBD9 565–567  BP9 396–399  PBD8 572–575  BP8 410–411 and ejection fraction with increased end-systolic volume.

5 1  A  Arrhythmogenic right ventricular cardiomyopathy PBD9 570  BP9 401  PBD8 577  BP8 413–414
(arrhythmogenic right ventricular dysplasia) is most likely
an autosomal dominant inherited condition with abnormal 5 5  A  Focal myocardial necrosis with a lymphocytic infiltrate
desmosomal adhesion proteins in myocytes. Infections of the is consistent with viral myocarditis. This is uncommon, and
heart are accompanied by inflammation, though a late find- many cases may be asymptomatic. In North America, most
ing in Chagas disease is ventricular fibrosis with ventricular cases are caused by coxsackieviruses A and B. This illness may
wall thinning. Hypertension leads to ventricular hypertro- often be self-limited. Less often, it ends in sudden death or pro-
phy. There is no characteristic gross or microscopic finding gresses to chronic heart failure. Mycobacterial infections of the
with long QT syndrome caused by myocyte channelopathies. heart are uncommon, but pericardial involvement is the most
Prior radiation therapy results in fibrosis, but it is not likely likely pattern. Septicemia with bacterial infections may involve
to be localized to the right ventricle; improving techniques the heart, but the patient probably would be very ill with multi-
that focus the beam and synchronize it with breathing motion ple organ failure. Viridans streptococci and Staphylococcus aure-
reduce cardiac damage when treating chest cancers. us are better known as causes of endocarditis with neutrophilic
inflammatory infiltrates. Toxoplasma gondii may cause myocar-
PBD9 568  PBD8 575–576  BP8 412 ditis with mixed inflammatory cell infiltrates in immunocom-
promised patients. Trypanosoma cruzi is the causative agent of
5 2  B  Hypertrophic cardiomyopathy is familial in >70% of Chagas disease, seen most often in children. This is probably the
cases and is usually transmitted as an autosomal dominant trait. most common infectious cause of myocarditis worldwide.
The mutations affect genes that encode proteins of cardiac con-
tractile elements. The most common mutation in the inherited PBD9 570–572  BP9 401–403  PBD8 578–579  BP8 414–416
forms affects the β-myosin heavy chain. Autoimmune condi-
tions are unlikely to involve the myocardium. Amyloidosis 5 6  C  Fibrinous pericarditis leads to the rough, corrugated
causes restrictive cardiomyopathy. Hemochromatosis can give brownish surfaces of epicardium and reflected pericardial
rise to cardiomyopathy, but it occurs much later in life. Viral in- sac as shown, which is sometimes described as a “bread and
fections produce generalized inflammation and cardiac dilation. butter” appearance (after dropping the buttered bread on the
carpet). Friction between epicardial and pericardial surfaces
PBD9 568–570  BP9 396–400  PBD8 575–577  BP8 412–413 yields the rub, which may disappear with fluid collection (se-
rofibrinous pericarditis). The most common cause is uremia re-
5 3  B  Hypertrophic cardiomyopathy is the most common sulting from renal failure. Elevation of the anti–streptolysin O
cause of sudden unexplained death in young athletes. There titer accompanies rheumatic fever. Acute rheumatic fever may
is asymmetric septal hypertrophy that reduces the ejection produce fibrinous pericarditis, but rheumatic fever is uncom-
fraction of the left ventricle, particularly during exercise. His- mon at this age. An elevated renin level is seen in some forms
tologically, haphazardly arranged hypertrophic myocardial of hypertension, but by itself does not indicate renal failure.

1 8 2 U N I T I I   Diseases of Organ Systems

Elevation of serum creatine kinase occurs in myocardial in- A large effusion can cause tamponade, which interferes with
farction. An acute myocardial infarction may be accompa- cardiac motion. Calcific aortic stenosis leads to left-sided con-
nied by a fibrinous exudate over the area of infarction, not the gestive heart failure, with pulmonary edema as a key finding.
diffuse pericarditis seen in this patient. A positive ANA test Coronary atherosclerosis may lead to myocardial infarction,
result suggests a collagen vascular disease, such as systemic which can be complicated by ventricular rupture and hemo-
lupus erythematosus, more likely associated with a serous pericardium, but the level of troponin I in this case suggests
pericarditis (without extensive fibrinous exudate). Fibrinous that infarction did not occur. Rheumatic heart disease mainly
pericarditis is unlikely the result of an infection, but a fibrino- affects the cardiac valves, but acute rheumatic fever can pro-
purulent appearance could suggest bacterial infection. duce fibrinous pericarditis. Tuberculosis is unlikely in this case
because no pulmonary lesions were seen on the radiograph.
PBD9 573–574  BP9 403–404  PBD8 581–582  BP8 396, 416
PBD9 574–576  BP9 404  PBD8 582  BP8 416–417
57  D  The clinical features are those of pericarditis with
effusion, and the most common causes of hemorrhagic pericardi- 6 0  C  Atrial myxoma is the most common primary cardi-
tis are metastatic carcinoma and tuberculosis. An effusion of this ac neoplasm. On the left side of the heart, it can produce a
size is sufficient to produce some cardiac tamponade that di- ball-valve effect that intermittently occludes the mitral valve,
minishes cardiac output; the paradoxical drop in pressure (more leading to syncopal episodes and possible strokes from embo-
than 10 mm Hg) is called pulsus paradoxus and can be caused by lization to cerebral arteries. Calcification of a bicuspid valve
pericarditis and by tamponade. Candida is a rare cardiac infec- can lead to stenosis and heart failure, but this condition is
tion in immunocompromised individuals. Coxsackieviruses are progressive. Coronary artery thrombosis results in an acute
known to cause myocarditis. Group A streptococci are respon- ischemic event, typically with chest pain. By the time left atri-
sible for rheumatic fever; in the acute form, rheumatic fever can al enlargement with mural thrombosis and risk of emboliza-
lead to fibrinous pericarditis, and in the chronic form, it can lead tion occurs from mitral stenosis, this patient would have been
to serous effusions from congestive heart failure. Staphylococcus symptomatic for years. Most pericardial effusions are not
aureus is most often a cause of infective endocarditis. large and do not cause major problems. Large effusions could
lead to tamponade, but this is not an intermittent problem.
PBD9 574  BP9 403–404  PBD8 581–582  BP8 416–417
PBD9 575–576  BP9 404–405  PBD8 583–584  BP8 417–418
58  A  The figure shows dark red blood filling the opened
pericardial cavity, a massive hemopericardium with peri- 61  E  Endomyocardial biopsies are routinely performed
cardial tamponade. After excluding trauma, a complication after cardiac transplantation to monitor possible immune
of ischemic heart disease should be suspected. Rupture of a rejection, and acute cellular rejection amenable to therapy
transmural myocardial infarction typically occurs 3 to 7 days with immunosuppression is described here. Turnover of cel-
after onset, when there is maximal necrosis before significant lular organelles occurs constantly by autophagy, generating
healing of the infarct. Ischemic heart disease occurs in patients lipofuscin pigment in the cells, but this slow process is not
of his age, and risk factors such as obesity, smoking, diabetes a feature of rejection. The transplant is foreign tissue to the
mellitus, and hyperlipidemia can play a role in its develop- host, so rejection is not an autoimmune process. Months to
ment. Cardiomyopathies lead to ventricular hypertrophy or years later, coronary arteriopathy characteristic of cardiac
dilation, or both, but do not cause rupture. Tuberculosis can transplantations may produce ischemic changes. Infection
cause hemorrhagic pericarditis, typically without tamponade. is a definite possibility because of the immunosuppressive
Scleroderma is most likely to produce serous effusion. Metas- drugs administered to control the rejection process, although
tases from melanoma and other carcinomas can produce hem- plasma cells are not a key feature of acute infection.
orrhagic pericarditis without tamponade. This patient does
not have a marfanoid habitus, although Marfan syndrome PBD9 577  BP9 405  PBD8 585  BP8 418–419
can cause cystic medial necrosis involving the aorta, leading
to aortic dissection that can cause an acute hemopericardium. 6 2  C  Nearly every allograft develops some degree of arte-
Takayasu arteritis can involve coronary arteries with aneu- riopathy within 10 years, and half of patients have significant
rysms and rupture, but is most often a rare pediatric condition. arteriopathy by 5 years following transplantation. Unlike ath-
erosclerosis, the smaller coronary artery branches are prefer-
PBD9 573  BP9 404  PBD8 581  BP8 396, 417 entially affected, but the result is the same: ischemic damage.
The inflammation that may come from rejection is not a risk for
5 9  C  Hemorrhagic pericardial effusion most commonly is amyloid deposition. A transplanted heart does not have a func-
caused by either tumor or tuberculosis. The most common neo- tional pericardial sac, and though there may be some fibrous
plasm involving the heart is metastatic cancer, because primary adhesions following surgery, they are not constrictive. Trans-
cardiac neoplasms are rare. The most common primary sites plant recipients receiving immunosuppressive therapy have
are nearby—lung, breast, and esophagus. The skin lesion in immune dysregulation that increases the risk for both carci-
this patient is likely to be a malignant melanoma, which tends nomas and lymphoid malignancies, but these are unlikely to
to metastasize widely, including to the heart. Most cardiac involve the heart. The immunosuppression with antirejection
metastases involve the epicardium/pericardium. (By conven- drugs increases the risk for infection with opportunistic agents,
tion, even though epicardial surfaces are often involved most but these are not common and they can often be treated.
severely, the term pericardial effusion is typically used when fluid
is present, or pericarditis is used when inflammation is present.) PBD9 577  BP9 405  PBD8 585  BP8 418

13C H A P T E R

Hematopathology of
White Blood Cells

PBD9 Chapter 13 and PBD8 Chapter 13: Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus

BP9 Chapter 11 and BP8 Chapter 12: Hematopoietic and Lymphoid Systems
  

1 A 14-year-old boy has a high fever of 10 days’ duration. D Escherichia coli
Physical examination shows a temperature of 38.3° C; pulse, E Herpes simplex virus
100/min; respiratory rate, 28/min; and blood pressure, 80/40 F Pneumocystis jiroveci
mm Hg. He has scattered petechial hemorrhages on the trunk G Toxoplasma gondii
and extremities. There is no enlargement of liver, spleen, or   
lymph nodes. The CBC shows hemoglobin, 13.2 g/dL; hema-
tocrit, 38.9%; MCV, 93 μm3; platelet count, 175,000/mm3; and 3 A 41-year-old man has had fevers with chills and rigors
WBC count, 1850/mm3 with 1% segmented neutrophils, 98% for the past 2 weeks. On physical examination, his temperature
lymphocytes, and 1% monocytes. Which of the following is is 39.2° C. CBC shows hemoglobin, 13.9 g/dL; hematocrit,
the most likely diagnosis? 40.5%; MCV, 93 μm3; platelet count, 210,000/mm3; and WBC
A Acute lymphoblastic leukemia count, 13,750/mm3 with the peripheral blood smear shown
B Acute myelogenous leukemia in the figure. A bone marrow biopsy specimen shows hyper-
C Aplastic anemia cellularity. Which of the following is most likely to cause these
D Idiopathic thrombocytopenic purpura findings?
E Systemic inflammatory response syndrome A Acute viral hepatitis
B Chronic myelogenous leukemia
2 A 29-year-old, HIV-positive woman has developed fever, C Glucocorticoid therapy
cough, and dyspnea over the past week. On physical exami­ D Lung abscess
nation, her temperature is 37.9° C. There is dullness to percus- E Splenomegaly
sion over lung fields posteriorly. A bronchoalveolar lavage is
performed, and cysts of Pneumocystis jiroveci are present. She
is given trimethoprim/sulfamethoxazole. One week later,
her respiratory status has improved. Laboratory studies now
show hemoglobin, 7.4 g/dL; hematocrit, 22.2%; MCV, 98 μm3;
platelet count, 47,000/mm3; and WBC count, 1870/mm3 with
2% segmented neutrophils, 2% bands, 85% lymphocytes, 10%
monocytes, and 1% eosinophils. One week later, she experiences
increasing dyspnea, and a chest CT scan shows multiple 1- to
3-cm nodules with hemorrhagic borders in all lung fields. These
nodules are most likely to be caused by infection with which of
the following organisms?
A Aspergillus fumigatus
B Bartonella henselae
C Mycobacterium avium complex

183

1 8 4 U N I T I I   Diseases of Organ Systems D Myelodysplastic syndrome
E Staphylococcus aureus abscess
4 A 23-year-old woman has noticed that she develops a
skin rash if she spends prolonged periods outdoors. She has a 8 A 36-year-old woman has a cough and fever for 1 week.
malar skin rash on physical examination. Laboratory studies On physical examination, her temperature is 38.3° C. She has
include a positive ANA test result with a titer of 1:1024 and a diffuse crackles in all lung fields. A chest radiograph shows
“rim” pattern. An anti–double-stranded DNA test result also bilateral extensive infiltrates. CBC shows hemoglobin, 13.9 g/
is positive. The hemoglobin concentration is 12.1 g/dL, hema- dL; hematocrit, 42%; MCV, 89 μm3; platelet count, 210,000/
tocrit is 35.5%, MCV is 89 μm3, platelet count is 109,000/mm3, mm3; and WBC count, 56,000/mm3 with 63% segmented neu-
and WBC count is 4500/mm3. Which of the following findings trophils, 16% bands, 7% metamyelocytes, 3% myelocytes, 1%
is most likely to be shown by a WBC differential count? blasts, 8% lymphocytes, and 2% monocytes. A bone marrow
A Basophilia biopsy is obtained and shows normal maturation of myeloid
B Eosinophilia cells. Which of the following is the most likely diagnosis?
C Monocytosis A Chronic myelogenous leukemia
D Neutrophilia B Hairy cell leukemia
E Thrombocytosis C Hodgkin lymphoma, lymphocyte depletion type
5 A 23-year-old man undergoing chemotherapy for acute D Leukemoid reaction
lymphoblastic leukemia has developed a fever and abdominal E Myelodysplastic syndrome
pain within the past week. He now has a severe cough. On   
physical examination, his temperature is 38.4° C. On ausculta-
tion, crackles are heard over all lung fields. Laboratory studies
show hemoglobin, 12.8 g/dL; hematocrit, 39%; MCV, 90 μm3;
platelet count, 221,000/mm3; and WBC count, 16,475/mm3
with 51% segmented neutrophils, 5% bands, 18% lympho-
cytes, 8% monocytes, and 18% eosinophils. Infection with
which of the following organisms is most likely to be compli-
cating the course of this patient’s disease?
A Cryptococcus neoformans
B Cytomegalovirus
C Pseudomonas aeruginosa
D Strongyloides stercoralis
E Toxoplasma gondii
F Varicella-zoster virus

6 A 28-year-old man is brought to the emergency depart- 9 A 23-year-old, previously healthy man has experienced
ment with shock that developed over the past 12 hours. On malaise and a low-grade fever and sore throat for 2 weeks.
physical examination, his temperature is 38.6° C, pulse is 101/ On physical examination, his temperature is 37.6° C, and he
min, respirations are 26/min, and blood pressure is 80/40 has pharyngeal erythema without exudation. There is tender
mm Hg. Needle tracks are noted in the left antecubital fossa. cervical, axillary, and inguinal lymphadenopathy. Laboratory
Crackles are heard over the lower lung fields. CBC shows hemo- studies show hemoglobin, 12.2 g/dL; hematocrit, 36.6%; platelet
globin, 14.1 g/dL; hematocrit, 42.6%; MCV, 93 μm3; platelet count, 190,200/mm3; and WBC count, 8940/mm3. His peripheral
count, 127,500/mm3; and WBC count, 12,150/mm3 with 71% blood smear is shown in the figure. Which of the following is
segmented neutrophils, 8% bands, 14% lymphocytes, and 7% the most likely risk factor for his illness?
monocytes. The neutrophils show cytoplasmic toxic granula- A Close personal contact (kissing)
tions and Döhle bodies. Which of the following is the most B Ingestion of raw oysters
likely diagnosis? C Inherited disorder of globin chain synthesis
A Acute myelogenous leukemia D Sharing infected needles for injection drug use
B Chronic myelogenous leukemia E Transfusion of packed RBCs
C Infectious mononucleosis
D Pneumocystis jiroveci pneumonia 10 A 6-year-old boy has complained of worsening pain in
E Pseudomonas aeruginosa septicemia the right side of his groin for the past week. Physical examina-
F Pulmonary Mycobacterium tuberculosis tion shows painful, swollen lymph nodes in the right inguinal
region. An inguinal lymph node biopsy is performed, and on
7 A 26-year-old man has had a fever with nonproductive microscopy the node has large, variably sized, germinal centers
cough for the past 10 weeks. On examination, his temperature containing numerous mitotic figures. There are numerous
is 37.4° C. A chest radiograph shows a 4-cm left upper lobe parafollicular and sinusoidal neutrophils. What is the most
nodule. CBC shows hemoglobin, 13.3 g/dL; hematocrit, 40.5%; likely cause of these histologic changes?
platelet count, 281,000/mm3; and WBC count, 13,760/mm3 A Acute lymphadenitis
with 38% segmented neutrophils, 2% bands, 45% lympho- B Acute lymphoblastic leukemia
cytes, and 15% monocytes. What is the most likely diagnosis? C Cat-scratch disease
A Acute lymphoblastic leukemia/lymphoma D Follicular lymphoma
B Hodgkin lymphoma, lymphocyte rich type E Sarcoidosis
C Mycobacterium tuberculosis granuloma F Toxoplasmosis

C H A P T E R 1 3   Hematopathology of White Blood Cells 1 8 5

11 A 39-year-old woman felt a lump in her breast 1 week C Hodgkin lymphoma, nodular sclerosing type
ago. On physical examination, she has a firm, fixed, irregular D Lymphoblastic lymphoma
3-cm mass in the upper outer quadrant of the right breast and E Mantle cell lymphoma
a firm, nontender lymph node in the right axilla. A lumpec- F Small lymphocytic lymphoma
tomy and axillary node dissection are performed, and micro- 15 A 70-year-old man has experienced increasing fatigue
scopic examination shows an infiltrating ductal carcinoma for the past 6 months. On physical examination, he has non-
in the breast. Flow cytometric analysis of the node shows a tender axillary and cervical lymphadenopathy, but there is no
polyclonal population of CD3+, CD19+, CD20+, and CD68+ hepatosplenomegaly. The CBC shows hemoglobin, 9.5 g/dL;
cells with no aneuploidy. Microscopic examination of the axil- hematocrit, 28%; MCV, 90 μm3; platelet count, 120,000/mm3;
lary lymph node is most likely to reveal changes characteristic and WBC count, 42,000/mm3. His peripheral blood smear
of which of the following conditions? shows a monotonous population of small, round, mature-
A Acute lymphadenitis looking lymphocytes. Flow cytometry shows these cells to
B Diffuse large B-cell lymphoma be CD19+, CD5+, and deoxynucleotid­ yl transferase negative
C Metastatic infiltrating ductal carcinoma (TdT−). Cytogenetic and molecular analysis of the abnormal
D Necrotizing granulomas cells in his blood are most likely to reveal which of the following
E Plasmacytosis alterations?
F Sinus histiocytosis A Clonal rearrangement of immunoglobulin genes
G Sézary syndrome B Clonal rearrangement of T-cell receptor genes
C t(8;14) leading to c-MYC overexpression
12 A 9-year-old, otherwise healthy girl has complained of D t(9;22) leading to BCR-ABL rearrangement
pain in the right armpit for the past week. Examination shows E t(14;18) leading to BCL2 overexpression
tender, enlarged lymph nodes in the right axillary region.   
There are four linear and nearly healed abrasions over a 3 ×
2 cm area of the distal ventral aspect of the right forearm and 16 A 69-year-old man notices the presence of lumps in
a single, 0.5-cm, slightly raised erythematous nodule over one the right side of his neck that have been enlarging for the
of the abrasions. No other abnormalities are noted. Histologic past year. Physical examination shows firm, nontender pos-
examination of one of the lymph nodes shows stellate, necro- terior cervical lymph nodes 1 to 2 cm in diameter. The over-
tizing granulomas. The lymphadenopathy regresses over the lying skin is intact and not erythematous. A lymph node is
next 2 months. Infection with which of the following is most biopsied and the microscopic appearance is shown in the
likely to have produced these findings? figure. Molecular analysis of the DNA extracted from the
A Bartonella henselae cells reveals B cell receptor gene rearrangements. Which of
B Cytomegalovirus the following features provides the best evidence for malig-
C Epstein-Barr virus nant lymphoma in this node?
D Staphylococcus aureus A Absence of a pattern of lymphoid follicles with
E Yersinia pestis
germinal centers
13 A study of persons with lymphoid malignancies reveals B Diminished sinusoidal plasma cells and
that there are risk factors for development of B-cell non-Hodgkin
lymphomas. Which of the following is the most likely inherited immunoblasts
condition predisposing to lymphoid malignancies? C Presence of CD30+ large, multinucleated cells
A Cystic fibrosis D Uniform expression of kappa, but not lambda, light
B Hereditary spherocytosis
C Sickle cell disease chains in the lymphoid cells
D Von Willebrand disease E Proliferation of small capillaries in the medullary
E Wiskott-Aldrich syndrome
and paracortical regions
14 A 14-year-old boy complains of discomfort in his chest
that has worsened over the past 5 days. On physical examina-
tion, he has generalized lymphadenopathy. A chest radiograph
shows clear lung fields, but there is widening of the medias-
tinum. A chest CT scan shows a 10-cm mass in the anterior
mediastinum. A biopsy specimen of the mass is obtained and
microscopically shows effacement by lymphoid cells with
lobulated nuclei having delicate, finely stippled, nuclear chro-
matin. There is scant cytoplasm, and many mitotic figures are
seen. The cells express deoxynucleoti­dyl transferase negative
(TdT−), CD2, and CD7 antigens. Molecular analysis reveals a
point mutation in the NOTCH1 gene. The oncologist tells the
parents that chemotherapy can be curative in vast majority of
such cases. What is the most likely diagnosis?
A Burkitt lymphoma
B Follicular lymphoma

1 8 6 U N I T I I   Diseases of Organ Systems 20 The figure skater Sonja Henie, who won gold medals
at the 1928, 1932, and 1936 Winter Olympic Games, became
17 A 4-year-old boy has appeared listless during the progressively fatigued in her late 50s. On physical examina-
past week. He exhibits irritability when his arms or legs are tion, she had palpable nontender axillary and inguinal lymph
touched. In the past 2 days, large ecchymoses have appeared nodes, and the spleen tip was palpable. Laboratory studies
on the right thigh and left shoulder. CBC shows hemoglobin, showed hemoglobin, 10.1 g/dL; hematocrit, 30.5%; MCV, 90
9.3 g/dL; hematocrit, 28.7%; MCV, 96 μm3; platelet count, μm3; platelet count, 89,000/mm3; and WBC count, 31,300/
45,000/mm3; and WBC count, 13,990/mm3. Examination of mm3. From the peripheral blood smear shown in the figure,
the peripheral blood smear shows blasts that lack peroxidase- which of the following is the most likely diagnosis?
positive granules, but contain PAS-positive aggregates and A Acute lymphoblastic leukemia
stain positively for deoxynucleotid­yl transferase negative B Chronic lymphocytic leukemia
(TdT−). Flow cytometry shows the phenotype of blasts to be C Infectious mononucleosis
CD19+, CD3−, and sIg−. Which of the following is the most D Iron deficiency anemia
likely diagnosis? E Leukemoid reaction
A Acute lymphoblastic leukemia
B Acute myelogenous leukemia 21 A 37-year-old man infected with HIV for the past 10 years
C Chronic lymphocytic leukemia is admitted to the hospital with abdominal pain of 3 days’ du-
D Chronic myelogenous leukemia ration. Physical examination shows abdominal distention and
E Idiopathic thrombocytopenic purpura absent bowel sounds. An abdominal CT scan shows a mass
lesion involving the ileum. He undergoes surgery to remove
18 A 7-year-old boy has complained of a severe headache an area of bowel obstruction in the ileum. Gross examination
for the past week. On physical examination, there is tender- of the specimen shows a firm, white mass, 10 cm long and 3
ness on palpation of long bones, hepatosplenomegaly, and cm at its greatest depth. The mass has infiltrated through the
generalized lymphadenopathy. Petechial hemorrhages are wall of the ileum. Histologic studies show a mitotically active
present on the skin. Laboratory studies show hemoglobin, population of CD19+ lymphoid cells with prominent nuclei
8.8 g/dL; hematocrit, 26.5%; platelet count, 34,700/mm3; and and nucleoli. Molecular analysis is most likely to show which
WBC count, 14,800/mm3. A bone marrow biopsy specimen of the following viral genomes in the lymphoid cells?
shows 100% cellularity, with almost complete replacement A Cytomegalovirus
by a population of large cells with scant cytoplasm lacking B Epstein-Barr virus
granules, delicate nuclear chromatin, and rare nucleoli. His C HIV
oncologist is confident that chemotherapy will induce a com- D Human herpesvirus 8
plete remission. Which of the following combinations of phe- E Human T-cell lymphotropic virus type 1
notypic and karyotypic markers is most likely to be present in
marrow cells from this boy?
A Early pre-B CD19+ hyperdiploidy
B Early pre-B CD20+ t(9;22)
C Pre-B CD5+ normal karyotype
D Pre-B CD23+ 11q deletion
E T cell CD2+ numerous blasts
F T cell CD3+ MLL gene translocation

19 A 66-year-old man has noted an increasing number and
size of lumps over his body in the past 5 months. On exami-
nation, there is firm, nontender inguinal, axillary, and cervi-
cal lymphadenopathy. A biopsy specimen of a cervical node
shows a histologic pattern of nodular aggregates of small,
cleaved lymphoid cells and larger cells with open nuclear chro-
matin, several nucleoli, and moderate amounts of cytoplasm.
A bone marrow biopsy specimen shows lymphoid aggregates
of similar cells with surface immunoglobulins that are CD10+,
but CD5−. Karyotyping of these lymphoid cells indicates the
presence of t(14;18). What is the most likely diagnosis?
A Acute lymphadenitis
B Hodgkin lymphoma, nodular sclerosis type
C Follicular lymphoma
D Mantle cell lymphoma
E Toxoplasmosis
  

C H A P T E R 1 3   Hematopathology of White Blood Cells 1 8 7

22 A 12-year-old boy has had increasing abdominal disten- his face. There is no lymphadenopathy or splenomegaly, and
tion and pain for the past 3 days. Physical examination of his he is afebrile. A biopsy of the mass is performed and micro-
abdomen shows lower abdominal tenderness with tympany scopic examination shows intermediate-sized lymphocytes
and reduced bowel sounds. An abdominal CT scan shows a with a high mitotic rate. A chromosome analysis shows a
7-cm mass involving the region of the ileocecal valve. Surgery 46,XY,t(8;14) karyotype in these cells. The hemoglobin concen-
is performed and the resected mass microscopically shows tration is 13.2 g/dL, platelet count is 272,000/mm3, and WBC
sheets of intermediate-sized lymphoid cells, with nuclei hav- count is 5820/mm3. Infection with which of the following vi-
ing coarse chromatin, several nucleoli, and many mitotic figures. ruses is most likely to be causally related to the development
A bone marrow biopsy sample is negative for this cell popu- of these findings?
lation. Cytogenetic analysis of the cells from the mass shows A Cytomegalovirus
a t(8;14) karyotype. Flow cytometric analysis reveals 40% of B Epstein-Barr virus
the cells are in S phase. The tumor shrinks dramatically after C Hepatitis B virus
a course of chemotherapy. Which of the following is the most D HIV
likely diagnosis? E Human papillomavirus
A Acute lymphoblastic leukemia/lymphoma F Respiratory syncytial virus
B Burkitt lymphoma   
C Diffuse large B-cell lymphoma
D Follicular lymphoma 26 A 61-year-old man reports back pain for 5 months. He
E Plasmacytoma has recently developed a cough that is productive of yellow
sputum. On physical examination, he is febrile, and diffuse
23 A 55-year-old man felt a lump near his shoulder 1 week rales are heard on auscultation of the lungs. He has no lymph-
ago. On physical examination, there is an enlarged, nontender, adenopathy or splenomegaly. Laboratory studies include a
supraclavicular lymph node and enlargement of the Waldeyer sputum culture growing Streptococcus pneumoniae. The serum
ring of oropharyngeal lymphoid tissue. There is no hepato- creatinine level is 3.7 mg/dL, and the urea nitrogen level is
splenomegaly. CBC is normal except for findings of mild ane- 35 mg/dL. The figure shows a skull radiograph. A bone mar-
mia. A lymph node biopsy specimen shows replacement by a row biopsy specimen from this man is most likely to show
monomorphous population of lymphoid cells that are twice the increased numbers of which of the following?
size of normal lymphocytes, with enlarged nuclei and promi- A Myeloblasts
nent nucleoli. Immunohistochemical staining and flow cytom- B Small mature lymphocytes
etry of the node indicates that most lymphoid cells are CD19+, C Plasma cells
CD10+, CD3−, CD15−, and terminal deoxynucleotidyl transfer- D Reed-Sternberg cells
ase negative (TdT−). A BCL6 gene mutation is present. Which of E Non-necrotizing granulomas
the following is the most likely diagnosis?
A Acute lymphoblastic lymphoma
B Chronic lymphadenitis
C Diffuse large B-cell lymphoma
D Hodgkin lymphoma
E Small lymphocytic lymphoma

24 A 62-year-old man has experienced vague abdominal
discomfort accompanied by bloating and diarrhea for the past
6 months. On physical examination, there is a midabdominal
firm mass. The stool is positive for occult blood. An abdominal
CT scan shows an 11 × 4 cm mass involving the wall of the
distal ileum and adjacent mesentery. A laparotomy is per-
formed, and the mass is removed. Microscopically, the mass is
composed of sheets of large lymphoid cells with large nuclei,
prominent nucleoli, and frequent mitotic figures. The neoplastic
cells mark with CD19+ and CD20+ and have the BCL6 gene
rearrangement. Which of the following prognostic features is
most applicable to this case?
A Aggressive, can be cured by chemotherapy
B Aggressive, often spreads to liver, spleen, and marrow
C Aggressive, often transforms to acute leukemia
D Indolent, can be cured by chemotherapy
E Indolent, often undergoes spontaneous remission
F Indolent, survival of 7 to 9 years without treatment

25 A 9-year-old boy living in Uganda has had increasing
pain and swelling on the right side of his face over the past 8
months. On physical examination, there is a large, nontender
mass involving the mandible, which deforms the right side of