4 3 8 U N I T I I Diseases of Organ Systems is done, and the CSF shows only a few mononuclear cells
and normal glucose and protein levels. Infection with which
38 A 4-year-old girl residing near Cape Town, South Africa, of the following organisms is the most likely cause of her
has had worsening headache and irritability for the past week, disease?
and now exhibits nausea, vomiting, and diminished respon- A Aspergillus niger
siveness to verbal commands. On examination she has a tem- B Cytomegalovirus
perature of 37.2° C. A tremor is observed in her extremities. Her C Herpes simplex virus
eyes do not move laterally. A lumbar puncture is performed D Eastern equine encephalitis virus
and examination of the CSF shows 100 leukocytes/mm3, and E Neisseria meningitidis
75% of them mononuclears. The CSF glucose is decreased, but
the protein is markedly elevated. CT imaging with enhance- 42 A 33-year-old woman, G3, P2, had two previous preg-
ment shows basilar meningeal thickening and a focal 2-cm nancies that resulted in normal term infants, but now she
mass involving the right cerebellar hemisphere. Which of the gives birth at 34 weeks’ gestation to a stillborn fetus. On
following infectious agents is most likely to produce these examination, the fetus is observed to be hydropic. Autopsy
findings? of the fetus shows marked organomegaly, and the brain has
A Coxsackie virus B extensive necrosis in a periventricular pattern, with focal
B Haemophilus influenzae calcifications. What congenital infection is most likely to
C Mycobacterium tuberculosis produce these findings?
D Treponema pallidum A Cytomegalovirus
E Taenia solium B Group B Streptococcus
39 A 65-year-old man has been noted by his family to be C Herpes simplex virus
more apathetic, irritable, and withdrawn over the past year. D HIV
He has worsening mental function. Neurologic examination E Listeria monocytogenes
shows a positive Romberg sign. His pupils constrict with near
focusing but not with exposure to light. He has delusions of 43 A 14-year-old girl, living in Nigeria, who has received
grandeur. He can remember only 1 of 3 objects after 5 minutes. poor prophylactic vaccines, develops mild diarrhea over 3 days,
CSF obtained from lumbar puncture shows a lymphocytic then has fever with neck stiffness and bilateral muscle weak-
pleocytosis and elevated protein with increased IgG. Which of ness. On examination muscle tenderness is present, with 3/5
the following organisms has most likely caused his illness? motor strength in all extremities. She has difficulty breathing
A Listeria monocytogenes that requires mechanical support of respiration. Over the next 6
B Rabies virus months the pain disappears and some muscle strength returns.
C Rubeola (measles) virus Which of the following nervous system structures has been
D Streptococcus pneumoniae affected most by her illness?
E Toxoplasma gondii A Anterior horns
F Treponema pallidum B Basal ganglia
40 A 26-year-old woman has headaches for 4 weeks C Corticospinal tracts
along with increasing malaise. Physical examination yields D Dorsal root ganglia
no remarkable findings. CT scan of the head shows no E Myoneural junctions
abnormalities. A lumbar puncture yields clear, colorless CSF F Neocortex
with a normal opening pressure. Laboratory analysis of the
CSF shows a normal glucose concentration and a minimally 44 A 12-year-old boy develops fever, accompanied by occa-
increased protein level. A few lymphocytes are present, sional headaches, malaise, fatigue, and nausea a month after
but there are no neutrophils. A Gram stain and India ink being bitten by a dog. One day later, he experiences episodes
preparation of the CSF are negative. Her condition gradually of rigidity, hallucinations, breath holding, and difficulty swal-
improves over the next 6 months. Serum serologic tests are lowing because of uncontrollable oral secretions. Dr. Louis
most likely to show an elevated titer of antibodies to which Pasteur is consulted. He writes: “The death of this child
of the following infectious agents? appearing to be inevitable, I decided, not without lively and
A Cryptococcus neoformans sore anxiety, as may well be believed, to try … the method
B Echovirus which I had found constantly successful with dogs. Conse-
C Listeria monocytogenes quently, 60 hours after the bites [the child] was inoculated
D Neisseria meningitidis under a fold of skin with half a syringeful of the spinal cord of
E Toxoplasma gondii a rabbit. In the following days, fresh inoculations were made.
41 A 25-year-old, previously healthy woman has acute I thus made 13 inoculations.” The boy survives. Which of the
onset of confusion and disorientation followed by a gen- following histologic findings in the brain of the dog is most
eralized tonic-clonic seizure. On admission to the hospital, likely to be present?
she is afebrile, and her blood pressure is 110/65 mm Hg. No A Multinucleate giant cells
papilledema is observed. Serum and urine drug screening B Negri bodies
results are negative. CT scan of the head shows a 3-cm recent C Perivascular lymphocytes
hemorrhage in the left temporal lobe. A lumbar puncture D Pseudocysts with bradyzoites
E Spongiform change
45 A 37-year-old man who is HIV-1-positive has had increas- C H A P T E R 2 8 Central Nervous System 4 3 9
ing memory problems for the past year. He is depressed. Dur-
ing the past 3 months, he has had increasing problems with 48 A previously healthy 21-year-old man with a severe
motor function and is now unable to stand or walk. For the headache for 5 days now has a new-onset seizure. Papilledema
past 3 days, he has had fever, cough, and dyspnea. A bron- is noted on funduscopic examination. An MRI of the brain
choalveolar lavage shows cysts of Pneumocystis jiroveci. MRI of shows multiple 0.5- to 1.5-cm cystic periventricular and men-
the brain shows diffuse cerebral atrophy; no focal lesions are ingeal lesions. Which of the following infectious organisms is
identified. On microscopic examination of his brain, which of most likely to produce these findings?
the following findings is most likely to be present? A Aspergillus fumigatus
A Cerebellar spongiform changes B Cryptococcus neoformans
B Cortical microglial nodules C Plasmodium falciparum
C Lentiform nuclear lacunar infarcts D Taenia solium
D Neocortical neuritic plaques E Toxoplasma gondii
E White matter plaques of demyelination F Trypanosoma gambiense
46 A 52-year-old woman with leukemia undergoes chemo-
therapy. Two months later, she develops neurologic deficits with 49 A 20-year-old HIV-positive man has had a decreased
ataxia, motor weakness in the right arm, difficulty swallowing, and level of consciousness for the past week. He now experiences
sensory changes in the left leg. MRI of the brain shows irregular a generalized tonic-clonic seizure. On physical examination,
areas of increased attenuation in white matter of the cerebral hemi- his temperature is 37.6° C. MRI of the brain shows several
spheres and the cerebellum. A stereotaxic biopsy specimen shows 1- to 3-cm, ring-enhancing lesions in the cerebral gray matter
perivascular chronic inflammation, marked gliosis, large reactive bilaterally. A stereotaxic biopsy is performed. What pathologic
astrocytes with bizarre nuclei, and intranuclear inclusions within finding is most likely to be present on microscopic examination
oligodendroglia. What virus most likely caused these findings? of the biopsy specimen?
A Cytomegalovirus A Budding cells with pseudohyphae
B Herpes simplex virus B Large atypical lymphocytes
C JC polyomavirus C Metastatic squamous cell carcinoma
D Rabies virus D Spongiform encephalopathy
E Rubeola virus E Toxoplasma pseudocysts
F West Nile virus
50 A 63-year-old previously healthy woman has become
more forgetful over a period of 6 weeks. One month later, she
47 A 38-year-old man with chronic renal failure received has difficulty ambulating and is unable to care for herself. On
a kidney transplant. While being treated with cyclosporine, physical examination, she has myoclonus. She is afebrile. CT
azathioprine, and high doses of corticosteroids, he began to scan of the head shows minimal cerebral atrophy. An EEG
experience headaches and became lethargic. On physical shows low-amplitude, slow background activity with peri-
examination, he now has a fever and nuchal rigidity. A lumbar odic complexes and occasional repetitive sharp waves with
puncture is performed and the opening pressure is increased. intervals of 0.5 to 1 second. Which of the following histologic
A CSF cell count shows increased leukocytes. An India ink abnormalities is most likely to be found in her cerebral cortex?
preparation shows the findings in the figure. Which of the fol- A Lewy bodies
lowing organisms is most likely infecting this man? B Microglial nodules
A Aspergillus niger C Numerous neuritic plaques
B Blastomyces dermatitidis D Plaques of demyelination
C Coccidioides immitis E Spongiform encephalopathy
D Cryptococcus neoformans
E Histoplasma capsulatum 51 A 27-year-old woman had an episode of weakness
3 months ago, which she attributed to job stress and fatigue.
The neurologic examination shows mild residual weakness,
with 4/5 motor strength in the right lower extremity. A
lumbar puncture is done, and laboratory examination of the
CSF shows increased IgG levels with prominent oligoclonal
bands. MRI of the brain shows small, scattered, 0.5-cm areas
consistent with demyelination, most of which are located in
periventricular white matter. Which of the following compli-
cations is she most likely to develop?
A Non-Hodgkin lymphoma
B Progressive dementia
C Quadriplegia
D Seizure disorder
E Tremor at rest
F Visual impairment
4 4 0 U N I T I I Diseases of Organ Systems 54 An 8-year-old boy recovered uneventfully from a viral
upper respiratory infection 2 weeks ago, but now has the
52 A 28-year-old man states that 3 years ago he experi- abrupt onset of lethargy and irritability. On neurologic exami-
enced paresthesias of his left arm and had difficulty walking, nation he has diminished pupillary reflexes bilaterally along
but these problems resolved. During the past year, he devel- with ataxia of his extremities. CSF obtained by lumbar punc-
oped difficulty seeing from his left eye. Six months ago, ture microscopically shows small numbers of lymphocytes
he had difficulty writing with his right hand. On physical and erythrocytes. MRI shows multiple hyperintense lesions
examination, there is decreased visual acuity on the left, no at the gray-white junction. Which of the following pathogenic
papilledema, and no retinal lesions. There is decreased motor mechanisms is most likely causing this child’s brain lesions?
strength and decreased sensation in the right hand and fore- A Abscess formation
arm. MRI of the brain shows focal areas of increased signal B Demyelination
intensity in periventricular white matter and in the left optic C Embolization
nerve. A lumbar puncture is performed. What finding is D Metastases
most likely to be present on examination of the CSF? E Thiamine deficiency
A Antitreponemal antibodies F Vasculitis
B Cryptococcal antigen
C Malignant cells
D Oligoclonal bands
E Xanthochromia
53 A 74-year-old woman sustains blunt head trauma in 55 A study is conducted of patients who had increased
a motor vehicle accident. On admission to the hospital, she phosphorylated tau and decreased Aβ peptide in their CSF
is conscious but disoriented. CT scan of the head shows a 5 to 10 years prior to death at ages ranging from 55 to 80 years.
right temporal bone fracture and mild cerebral edema. Her At autopsy their brain weights are less than normal for age and
blood alcohol level is 0.24 gm%. Two days later, laboratory body size. On gross examination, these brains show hydro-
studies show serum Na+, 109 mmol/L; K+, 3.9 mmol/L; Cl−, cephalus ex vacuo and cortical atrophy but no focal lesions.
82 mmol/L; CO2, 23 mmol/L; glucose, 73 mg/dL; and creatinine, The figure shows the high power microscopic appearance of
1 mg/dL. The hyponatremia is corrected over the next 2 hours cerebral neocortex with Bielschowsky silver stain. Which of
with intravenous fluid and electrolyte therapy and diuretics. the following symptoms is most likely to be recorded in the
She then rapidly becomes confused and exhibits limb weak- medical histories of these patients?
ness. No papilledema is seen on funduscopic examination. An A Choreiform movements
MRI shows the finding in the figure. What complication has B Gait disturbances
most likely occurred in this woman? C Grand mal seizures
A Central pontine myelinolysis D Progressive memory loss
B Cerebellar tonsillar herniation E Symmetric muscular weakness
C Intraventricular hemorrhage
D Subacute combined degeneration of the cord
E Wernicke-Korsakoff syndrome
56 A 68-year-old woman with a 7-year history of progressive C H A P T E R 2 8 Central Nervous System 4 4 1
dementia dies of bronchopneumonia. At autopsy, there is cerebral
atrophy in a predominantly frontal and parietal lobe distribution. 59 A 55-year-old man has had increasing difficulty with
Microscopic examination of the brain shows numerous neuritic initiation of voluntary movements and increasing inability
plaques in the hippocampus, amygdala, and neocortex. Neuro- to perform activities of daily living for 1 year. On physical
fibrillary tangles in the hippocampus contain tau protein. Congo examination, he has difficulty initiating movement, but he
red staining shows amyloid in the media of the small peripheral can keep moving if he follows someone walking ahead of
cerebral arteries. Which of the following genetic abnormalities is him. He has an expressionless facies. The left side of the
the most important factor in the development of her disease? figure shows the gross appearance of the midbrain of this
A Expansion of CAG repeats on chromosome 4p16 patient; on the right is a section through normal midbrain.
B HLA-DR3/DR4 alleles What additional clinical feature is most closely associated
C Increased tandem repeats in the FMR1 gene with this abnormality?
D Mutation of a prion protein gene A Ataxia with ambulation
E Presence of the e4 allele at the ApoE gene B Choreiform movements
C Loss of short-term memory
57 A 63-year-old man had increasing irritability over D Symmetric weakness in the extremities
3 years. He wandered about his neighborhood, complain- E Tremor at rest
ing to the neighbors about everything. He had no memory 60 A 47-year-old woman from Venezuela has had diffi-
loss and was always able to find his way home. The neigh- culty performing activities of daily living for the past year.
bors were pleased when he developed aphasia. On physical She is emotionally labile and often cries. She is disturbed and
examination, there were no motor or sensory deficits and no depressed by these developments because her mother and
gait disturbances or tremor. MRI of the brain showed bilateral brother died 5 years after experiencing the same symptoms.
marked temporal and frontal lobe gyral atrophy. He died of On physical examination, she has choreiform movements of
pneumonia 1 year later. At autopsy, the frontal cortex micro- her extremities. Cranial nerves are intact. She has no motor
scopically shows extensive neuronal loss, and some remaining weakness and no sensory deficits. Her memory remains
neurons show intracytoplasmic, faintly eosinophilic, rounded intact. Which of the following genetic abnormalities is most
inclusions that stain immunohistochemically for tau protein. likely to be present in this woman?
What is the most likely diagnosis? A Abnormal prion protein
A Alzheimer disease B Decreased level of hexosaminidase A enzyme
B Huntington disease C Extra chromosome 21
C Leigh disease D Expansion of CAG repeats
D Multiple system atrophy E Mutation in presenilin genes
E Parkinson disease 61 A 4-year-old girl developed clumsiness and difficulty
F Pick disease ambulating over 6 months. On physical examination, she
G Vascular dementia showed difficulty with balance while walking, dysarthria,
poor hand coordination, absent deep tendon reflexes, and a
58 A 60-year-old woman had problems related to move- bilateral Babinski sign. Light touch and vibratory sensation
ment for 5 years. Physical examination showed cogwheel were greatly diminished. There was no muscular weakness.
rigidity of limbs and a festinating gait, which she had diffi- Over the next 5 years, she developed congestive heart failure
culty initiating. Her face was expressionless. She was given from hypertrophic cardiomyopathy. She also had hyper-
levodopa/carbidopa, and her condition improved. Two years glycemia. At autopsy, there was increased perinuclear iron
later, she had difficulty performing activities of daily living deposition within cardiac myocytes. Which of the following
and showed marked cognitive decline. She died of aspiration genetic abnormalities with trinucleotide repeat expansions
pneumonia. Autopsy findings include mild cerebral atrophy was most likely present in this patient?
and loss of substantia nigra pigmentation. Microscopically, A CAG repeats in the huntingtin gene
cortical neurons show spheroidal, intraneuronal, cytoplasmic, B CGG repeats in the FMR1 gene
and eosinophilic inclusions. Immunohistochemical staining C CTG repeats in the dystrophila myotonia-protein
for which of the following proteins is most likely to be posi-
tive in these inclusions? kinase gene
A α-Synuclein D GAA repeats in the frataxin gene
B Amyloid precursor protein
C Apolipoprotein E
D Huntingtin
E Presenilin
F Tau protein
4 4 2 U N I T I I Diseases of Organ Systems 66 A 55-year-old man has experienced headaches for the
first time in his life beginning 2 months ago. He comes to the
62 A 36-year-old man who had been healthy all his life now emergency department following a generalized tonic-clonic
has progressive, symmetric muscular weakness. A year ago, seizure. On physical examination, he has weakness on the left
he noted weakness in the area of the head and neck, which side. An MRI of his brain shows a large, irregular, 6-cm mass
caused difficulty with speech, eye movements, and swallow- in the centrum semiovale of the right cerebral hemisphere that
ing. In the past year, the weakness in the upper and lower extends across the corpus callosum. A stereotaxic biopsy of
extremities has increased, and he can no longer stand, walk, or the mass is done and microscopically shows pleomorphic cells
feed himself. His mental function remains intact. Which of the positive for glial fibrillary acidic protein (GFAP). Molecular
following cells is most likely being destroyed in this man? analysis shows abnormalities of TP53 and platelet-derived
A Ependymal cell growth factor-alpha (PDGF-α). Which of the following neo-
B Lower motor neuron plasms is he most likely to have?
C Microglial cell A Diffuse large B-cell lymphoma
D Oligodendrocyte B Glioblastoma
E Pigmented neuron C Hemangioblastoma
F Spiny neuron D Medulloblastoma
E Pilocytic astrocytoma
63 A 12-year-old girl has had progressively diminishing
neurologic function over 3 years. She has difficulty with ambula- 67 A 10-year-old boy has had persistent headaches for the
tion, decreased mental ability, seizures, and loss of control over past 3 months. On physical examination, he is afebrile. He has
bladder and bowel functions. An MRI of her brain shows atro- an ataxic gait and dysdiadochokinesia. CT scan of the head
phy, and the centrum semiovale and central white matter are shows a 4-cm cystic mass in the right cerebellar hemisphere.
shrunken. These findings correlate with widespread microscopic Cerebral lateral ventricles are enlarged. A lumbar puncture is
myelin loss, but sub-cortical myelin is spared. Which of the fol- done. The CSF protein concentration is elevated, but the glu-
lowing degenerative CNS diseases best explains her illness? cose level is normal. Neurosurgery is performed, and the mass
A Acute disseminated encephalomyelitis is removed and sectioned. On gross examination, the mass
B Metachromatic leukodystrophy is a cyst filled with gelatinous material. The cyst has a thin
C Multiple sclerosis wall and a 1-cm mural nodule. Microscopically, the mass is
D Progressive multifocal leukoencephalopathy composed of cells that stain positive for glial fibrillary acidic
E Tay-Sachs disease protein (GFAP) and have long, hairlike processes. What is the
most likely diagnosis?
64 A 49-year-old man develops an acute psychosis. He A Astrocytoma
has a lengthy history of chronic alcoholism. He has difficulty B Ependymoma
performing a finger-to-nose test, and there is paralysis of the C Hemangioblastoma
lateral rectus muscles. A deficiency of which of the following D Medulloblastoma
nutrients is most likely to produce these findings? E Meningioma
A Cobalamin F Schwannoma
B Folate
C Niacin 68 A 40-year-old man has been experiencing headaches
D Pyridoxine for the past 6 months. He had a seizure 1 day ago. On physi-
E Thiamine cal examination, there are no remarkable findings. MRI of the
brain shows a solitary, circumscribed 3-cm mass in the right
65 A 53-year-old man with a lengthy history of chronic parietal centrum semiovale. The mass has small cysts and
alcohol abuse has had an increasingly clouded sensorium over areas of calcification and hemorrhage. Neurosurgery is per-
the past 2 days. On physical examination, he has a flapping formed, and the mass is removed. Microscopically, the mass
tremor of his outstretched hands. MRI of the brain shows no consists of sheets of cells with round nuclei that have granular
abnormalities. Microscopic examination of his brain would chromatin. The cells have a moderate amount of clear cyto-
show increased numbers of neocortical and basal ganglia plasm, and they mark with GFAP by immunohistochemical
astrocytes with pale, swollen nuclei (Alzheimer type II cells). staining. The patient receives adjuvant radiation and chemo-
Which of the following laboratory findings in his blood is most therapy, and there is no recurrence. Which of the following
likely to be associated with these findings? molecular markers is most likely to be found in the cells of this
A Ammonia level of 100 µmol/L mass?
B Carboxyhemoglobin level of 5% A BRAF mutation
C Glucose of 30 mg/dL B CD20 expression
D Hemoglobin A1c level of 10% C c-MYC amplification
E Sodium of 111 mmol/L D EGFR amplification
E 1p and 19q co-deletions
69 A 46-year-old woman has had increasing weakness and C H A P T E R 2 8 Central Nervous System 4 4 3
loss of sensation in the lower extremities for the past 5 months. mark with CD19, but not with GFAP or cytokeratin. What is
She has been unable to walk without assistance for the past the most likely diagnosis?
week. On physical examination, there is 4/5 motor strength A Cytomegalovirus encephalitis
in the right lower extremity and 3/5 motor strength in the left B Glioblastoma
lower extremity. There is bilateral loss of sensation to light C Kaposi sarcoma
touch from the lateral midthigh distally. MRI of the spine D Large B-cell lymphoma
shows a 1 × 4 cm lesion in the filum terminale. The mass is E Progressive multifocal leukoencephalopathy
removed. Microscopically, the mass is composed of cuboidal F Toxoplasmosis
cells around papillary cores in a myxoid background. Which
of the following lesions was most likely present in this patient?
A Choroid plexus papilloma 73 A 45-year-old woman has had unilateral headaches on
B Ependymoma the right for the past 5 months. Physical examination yields no
C Meningioma remarkable findings. The representative gross appearance of
D Neurofibroma the lesion seen on CT scan of the head is shown in the figure.
E Pilocytic astrocytoma The mass is surgically removed and microscopic examination
F Schwannoma shows elongated cells with pale, oblong nuclei and pink cyto-
plasm with occasional psammoma bodies. Cytogenetic analysis
70 An 11-year-old girl has had increasing headaches upon shows 22q-. What is the most likely diagnosis?
awakening for the past month. On examination, papilledema A Astrocytoma
is present bilaterally. An MRI of her brain reveals a 3-cm solid B Ependymoma
circumscribed mass within the fourth ventricle. There is third C Meningioma
and lateral cerebral ventricular dilation. The mass is excised D Metastasis
and microscopically shows perivascular pseudorosettes with E Tuberculoma
round, regular tumor cells arranged around vessels. Which of 74 A 76-year-old man has a single episode of grand mal
the following neoplasms is she most likely to have? seizure. On physical examination, he is afebrile and normo-
A Astrocytoma tensive. Motor strength is intact, and there is no loss of sen-
B Ependymoma sation. Cranial nerves are intact. His mental function is not
C Glioblastoma diminished. There is a 1-cm, darkly pigmented skin lesion
D Medulloblastoma on the upper back. Brain MRI shows three solid, 1- to 3-cm
E Schwannoma mass lesions, without ring enhancement or surrounding
edema, located at the gray-white junction in the right and
71 A 5-year-old boy has complained of headaches for the left frontal lobes. The cerebral ventricles appear normal in
past week. His gait has become ataxic. After sudden onset of size. What is the most likely diagnosis?
vomiting, he is brought to the emergency department, where A Glioblastoma
he becomes comatose. On physical examination, he is afebrile. B Hemangioblastoma
A lumbar puncture is done and cytologic examination of the C Meningioma
CSF shows anaplastic cells with dark blue nuclei and scant D Metastatic carcinoma
cytoplasm. An MRI is most likely to show a mass in which of E Non-Hodgkin lymphoma
the following locations? F Oligodendroglioma
A Centrum semiovale
B Cerebellar vermis
C Cranial nerve VIII
D Fourth ventricle
E Parietal lobe gray-white junction
72 A 39-year-old HIV-positive man has received no anti-
retroviral therapy. He has had left-sided weakness for the
past month and experienced a generalized seizure a day ago.
On physical examination, he is afebrile. CT scan of the head
shows no intracranial hemorrhage, but there is a midline shift.
MRI of the brain shows a 4-cm mass in the region of the puta-
men near the right internal capsule, a 3-cm mass in the right
centrum semiovale, and a 1-cm mass near the splenium of the
corpus callosum. These masses are circumscribed and solid.
CSF from a lumbar puncture shows an elevated protein con-
centration and a normal glucose level. Cytologic examination
shows large cells with large nuclei and scant cytoplasm that
4 4 4 U N I T I I Diseases of Organ Systems 77 A 20-year-old woman with learning difficulties had
flank pain for 1 week. Physical examination showed right cos-
75 An 18-year-old student has had decreased vision in tovertebral angle tenderness. Patches of leathery-appearing
her right eye for 6 months. On physical examination, there (shagreen patches) and hypopigmented (ash-leaf patches) skin
is papilledema on the right. She has 14 scattered, 2- to 5-cm were scattered over her body. There was a subungual nodule
flat, hyperpigmented skin lesions with irregular borders on on her right index finger. Abdominal CT scan showed bilat-
the extremities and torso. CT scan of the head shows no intra- eral renal cysts and tumor masses. MRI of the brain showed
cranial hemorrhage and no edema or midline shift, but there subependymal nodules and 1- to 4-cm cortical foci with loss
is a mass in the region of the right optic nerve. An optic nerve of the gray-white distinction. CT scan of the chest showed a
glioma is excised. Eight months later, she returns for a follow- 3-cm mass involving the interventricular septum. Two years
up examination, and a mass is palpated on the right wrist. later, she now has sudden, severe headache. MRI now shows
Histologic examination of the mass is most likely to show a nodule obstructing the cerebral aqueduct. Neurosurgery
which of the following neoplasms? is performed, and a subependymal giant cell astrocytoma is
A Fibrosarcoma removed. What is the most likely diagnosis?
B Lipoma A Down syndrome
C Hemangioma B Krabbe disease
D Meningioma C Neurofibromatosis type 1
E Schwannoma D Neurofibromatosis type 2
76 A 41-year-old woman has had diminished hearing for E Tuberous sclerosis
the past 4 months. On physical examination, she has decreased F Von Hippel–Lindau disease
hearing on the left. Sound lateralizes to the right ear on the
Weber tuning fork test. A head MRI shows a sharply cir- 78 A study of adults with cerebellar neoplasms reveals that
cumscribed, 4-cm mass adjacent to the left pons that extends some of them have an autosomal dominant inheritance pat-
toward the left inferior cerebellar hemisphere. A smaller 1-cm tern with von Hippel–Lindau disease. Their cerebellar tumors
lesion is in a similar location on the right. Family screening are cystic with a mural nodule. Molecular analysis of tumor
reveals a similarly affected 38-year-old sibling. An inherited cells shows increased amounts of hypoxia-inducible factor
mutation involving which of the following genes is most likely (HIF). The incidence of renal cell carcinomas is increased in
to be present in this patient? these persons. Which of the following paraneoplastic manifes-
A NF2 tations is most likely to be found in these adults?
B TP53 A Cushing syndrome
C PTCH B Hypercalcemia
D TSC1 C Polycythemia
E VHL D Syndrome of inappropriate ADH
E Trousseau syndrome
ANSWERS 3 C The papilledema and the herniation are a consequence
of brain swelling, typically the vasogenic form of edema from
1 D Hypoxic and hypoglycemic injury leads to “red” neu- blood-brain barrier disruption adjacent to the neoplasm. A large
rons as the initial reaction. The larger pyramidal neurons aggressive neoplasm, such as a glioblastoma, may produce a
are the most sensitive, particularly in the hippocampus with mass effect via enlargement from rapid growth, hemorrhage,
hypoglycemia, as well as neocortical Betz cells and cerebel- and surrounding edema. The mass effect with herniation of
lar Purkinje cells. Astrocytes proliferate in reaction to brain the medial temporal lobe results in a third cranial nerve palsy
injury in the process called gliosis. Endothelial cells are most as the nerve is compressed. A chronic subdural hemorrhage
likely to proliferate in neoplasms. Microglia respond to brain accumulates slowly enough that herniation may not occur. An
injury with a macrophage-like function. Oligodendroglial abscess may cause a mass effect with some associated brain
cells provide myelination for brain neuronal axons. swelling, but this patient is afebrile. There is no pressure effect
with hydrocephalus ex vacuo, which is a consequence of cere-
PBD9 1252 BP9 811 PBD8 1281 BP8 860 bral atrophy. An infarct is not likely to produce pronounced
associated brain swelling, and a mass effect in occipital lobe is
2 D Microglial cells are part of the body’s fixed macrophage unlikely to affect the third nerve. Rupture of a berry aneurysm
system, derived originally from mesoderm. Microglia can produces subarachnoid hemorrhage at the base of the brain,
respond to cerebral injuries by taking on a macrophage-like which is less likely to cause a mass effect.
function. The arachnoid layer is part of the meninges cover-
ing the brain. Astrocytes can proliferate in response to brain PBD9 1254–1255 BP9 812–813 PBD8 1282–1283 BP8 861–863
injuries, a process called gliosis, but there is no phagocytosis.
Ependymal cells line the ventricular system containing CSF. 4 D This is noncommunicating hydrocephalus with ob
Oligodendroglial cells provide the myelin sheaths for neuro- struction below the level of the third ventricle. If hydroceph-
nal axons in the CNS. alus had been present at birth, there would be increasing
PBD9 1253 BP9 811–812 PBD8 1282 BP8 861
C H A P T E R 2 8 Central Nervous System 4 4 5
head size because the sutures are not yet closed, and con- not narrowing. Subarachnoid hemorrhage is most likely a
genital aqueductal stenosis would be suspected. At his age, consequence of a ruptured berry aneurysm, without a mass
a neoplasm should be suspected, and ependymomas arise in effect.
the ventricular system, often in the fourth ventricle, to cause
obstruction of CSF flow. The increased CSF protein comes PBD9 1254 BP9 813 PBD8 1282 BP8 861
from this tumor, but shedding of cells from the mass into
the CSF is unlikely. Except for vascular malformation, the 8 B The figure shows linear midline hemorrhages, called
other options are uncommon at his age. An abscess is typi- Duret hemorrhages, in the pons. The acute bacterial meningi-
cally accompanied by fever, and most would be located in tis led to brain swelling with edema and subsequent hernia-
the cerebral hemispheres away from the ventricular sys- tion of medial temporal lobe with Duret hemorrhages in the
tem. Cryptococcal meningitis is accompanied by fever, and pons. Although not seen in this figure, an infection could
exudate can be found within the ventricular system and organize with scarring of foramina to produce a noncom-
subarachnoid space, but there is more likely to be cerebral municating hydrocephalus, or it could scar the vertex and
edema, not hydrocephalus. The demyelinating plaques of impair reabsorption of CSF at the arachnoid granulations to
multiple sclerosis are small and do not usually act as mass produce a communicating hydrocephalus. An abscess infre-
lesions. Vascular malformations usually arise in the cerebral quently complicates meningitis; conversely, an abscess in a
hemispheres. paranasal sinus or mastoid air cell may extend into the cra-
nial cavity to cause meningitis. Laminar necrosis could occur
PBD9 1254–1255 BP9 812–813 PBD8 1283 BP8 861–862, 884 after brain death, but this finding is not specific for meningi-
tis. The small meningeal vessels do not often bleed because
5 F He has communicating hydrocephalus, and pneumo- of inflammation caused by meningitis.
coccal meningitis in adults often involves the vertex, where
the arachnoid granulations that reabsorb CSF are found. PBD9 1255 BP9 814 PBD8 1284 BP8 862–863
Overproduction of CSF from a choroid plexus papilloma may
also produce hydrocephalus, but is rare. Non-communicating 9 B Anencephaly is a form of severe neural tube defect
hydrocephalus occurs when there is obstruction within the that results from failure of formation of the fetal cranial vault.
ventricular system. Both aqueductal stenosis and Dandy- This is one of the most common CNS malformations seen at
Walker malformation are congenital conditions causing birth. The defect allows fetal α-fetoprotein to enter amniotic
ventricular system obstruction. Cerebral infarcts and HIV fluid and reach the maternal circulation. The karyotype listed
infection produce lesions within the brain parenchyma, and is that of a Robertsonian Down syndrome carrier; Down syn-
are unlikely to obstruct the CSF flow unless there is a mass drome (trisomy 21) may be associated with brachycephaly,
effect (from edema or hemorrhage with the infarction, or a but rarely with anencephaly. Congenital cytomegalovirus
CNS lymphoma with AIDS), but no mass was noted in this infection can produce extensive fetal brain parenchymal
man’s CT scan. necrosis, but not loss of the fetal cranial vault. Neural tube
defects are not associated with maternal or neonatal jaundice.
PBD9 1254–1255 BP9 813 PBD8 1283 BP8 861–862 Diabetes mellitus, suggested by an elevated hemoglobin A1c
concentration, can increase the risk of malformations (e.g.,
6 A Her contralateral right leg weakness is a consequence holoprosencephaly in the CNS), but not neural tube defects.
of subfalcine herniation with compression of the ipsilateral
anterior cerebral artery caused by a lesion in the adjacent PBD9 1256 BP9 822–823 PBD8 1284 BP8 872
frontal lobe. A rapidly expanding mass lesion can lead to
herniation. The other listed options, above the tentorium, 10 D Holoprosencephaly is a midline defect in which
are much less likely to explain anterior cerebral artery com- there is absent (alobar) or partial (semilobar) cerebral hemi-
pression. Frontal lobe lesions might account for transtento- spheric development. It can occur in trisomy 13, as in this
rial herniation. A very large mass effect above the tentorium case, with other midline defects. It also may be seen in cases
could also produce tonsillar herniation. of maternal diabetes mellitus. Anencephaly is the absence of
a fetal cranial vault, which leads to absence of most of the
PBD9 1255 BP9 813–814 PBD8 1283 BP8 862 brain. Arnold-Chiari II malformation results in a small poste-
rior fossa, a misshapen midline cerebellum with downward
7 B Cerebral edema may be cytotoxic or vasogenic. In displacement of the vermis, and tenting of the tectal plate.
cytotoxic edema the blood-brain barrier remains intact, and Dandy-Walker malformation is characterized by aplasia
edema is due to failure of ATP-dependent ion transport with or hypoplasia of the cerebellar vermis, cystic enlargement
cellular retention of sodium and water. Global processes of the fourth ventricle, and hydrocephalus. Periventricular
such as ischemia (from heart failure in this case) or meta- leukomalacia is a form of perinatal injury that is caused by
bolic derangements are implicated, and consistent with dif- hypoxic-ischemic events or infections.
fuse swelling with bilateral papilledema. Inflammation and
neoplasms are more likely to produce vasogenic edema. An PBD9 1257 BP9 823 PBD8 1285 BP8 872
acute meningitis might produce diffuse swelling, but there
are no signs of infection here. Metastases are unlikely to pro- 11 E The syrinx is a tubular defect that extends laterally,
duce rapidly expanding mass lesions. Obstruction of CSF disrupting the spinothalamic tracts and anterior horns, pro-
flow leads to hydrocephalus with ventricular enlargement, ducing sensory and motor deficits. When the cavity extends
4 4 6 U N I T I I Diseases of Organ Systems
into the medulla, it is called syringobulbia. There is no treat- to degenerative white matter changes, typically with meta-
ment, but the lesion tends not to progress. Dandy-Walker bolic and infectious insults. Post-traumatic dementia from
malformation is a congenital condition with an enlarged repeated blows to the head often has pathologic findings
posterior fossa. Diffuse axonal injury involves white matter of neurofibrillary tangles and neuritic plaques similar to
tracts in the cerebrum. Rachischisis is a large open neural Alzheimer disease.
tube defect. Spina bifida is a posterior neural tube defect.
PBD9 1259 BP9 820 PBD8 1288 BP8 869
PBD9 1258 BP9 823 PBD8 1286 BP8 873
1 5 E This patient has the classic “contrecoup” type of
1 2 A Arnold-Chiari II malformation has features includ- injury, in which the moving head strikes an object, and the
ing in a small posterior fossa, misshapen midline cerebellum force is transmitted to the opposite side of the head. A fall
with downward displacement of the vermis, and tenting of backward is most likely to produce contusions to the inferior
the tectal plate, leading to hydrocephalus. MRI in this case is frontal lobes, temporal tips, and inferior temporal lobes. A
characteristic of hydromyelia. Cerebral palsy is a general term blow to a stationary head is more likely to produce a “coup”
describing nonprogressive motor deficits that are present injury directly adjacent to the site of the blow. Basal ganglia
from birth. The corpus callosum is seen in the figure; agene- putaminal hemorrhage is most likely to occur in hyperten-
sis may be associated with other anomalies, or may be found sion. Hemorrhage into the pons is typical of a Duret hemor-
in normal persons. Holoprosencephaly is a severe malforma- rhage, seen in medial temporal lobe herniation. Hemorrhage
tion with total (alobar) or incomplete (semilobar) separation into the cerebral ventricles may occur in premature infants
of the cerebral hemispheres in brain development. Polymi- from germinal matrix hemorrhage; in adults, it is uncom-
crogyria is characterized by numerous small, irregularly mon, but may occur with dissection of blood from an intra-
formed gyral contours. parenchymal lesion. A blow to the side of the head is more
likely to lacerate the middle meningeal artery and produce
PBD9 1258 BP9 823 PBD8 1285–1286 BP8 872 an epidural hematoma. Subarachnoid hemorrhage at the
base of the brain may dissect into the sella.
1 3 C Germinal matrix hemorrhage is the most common
cause of intraventricular hemorrhage in premature infants. PBD9 1260 BP9 820–821 PBD8 1287–1288 BP8 869
The germinal matrix, composed of highly vascularized tis-
sue with primitive cells, is most prominent between 22 and 16 C The “lucid” interval is a classic feature of an epi-
30 weeks’ gestation. Hemorrhages within this area read- dural hematoma with rapid accumulation of blood from
ily occur with common neonatal problems such as hypox- the injured middle meningeal artery. The dura is pushed
emia, hypercarbia, acidosis, and changes in blood pressure. against the brain, producing the lens-shaped blood collec-
Hemorrhages in the germinal matrix can extend into the tion seen with radiologic imaging, particularly CT imaging.
cerebral ventricles and from there into the subarachnoid Leptomeningitis is not associated with trauma. Contusions
space. Smaller hemorrhages can resolve without sequelae. do not progressively worsen. In an acute subdural hema-
With larger hemorrhages, organization of the blood in the toma or a ruptured aneurysm, there typically is no lucid
aqueduct of Sylvius or the fourth ventricle or foramina interval, but instead a sudden and progressive worsening
of Luschka and Magendie may obstruct the flow of CSF, of symptoms.
producing hydrocephalus. Cytomegalovirus infection can
cause considerable necrosis of the brain parenchyma, par- PBD9 1261–1262 BP9 821 PBD8 1289 BP8 870–871
ticularly in a periventricular location, but not hemorrhage
with obstruction of CSF flow. Infants with Down syndrome 17 E A subdural hematoma results from tearing of the
may have vascular malformations that can bleed into the bridging veins beneath the dura. These veins are at risk of
parenchyma. The bilirubin staining of kernicterus does not tearing with head trauma, particularly in elderly individu-
result in meningeal or aqueductal scarring. Medulloblasto- als, in whom some degree of cerebral atrophy may be pres-
mas are aggressive posterior fossa tumors that occur in chil- ent. Bleeding from low-pressure veins produces a variable
dren (not typically in infants) that could cause obstruction time course for appearance of signs and symptoms, from
of CSF flow. hours to days to weeks. Basal ganglia hemorrhages are most
often associated with hypertension. Epidural hemorrhages
PBD9 1259 BP9 824 PBD8 1286 BP8 873 are most often preceded by a blow to the head that tears
the middle meningeal artery; there is commonly a “lucid”
1 4 B Concussion leads to altered consciousness, starting interval between an initial loss of consciousness occurring
with instantaneous onset of transient neurologic dysfunction with trauma and the later accumulation of blood. Pontine
with head trauma, amnesia for the event, then neurologic hemorrhages are likely to be Duret hemorrhages. Subarach-
recovery or post-concussion syndrome with disabling neuro- noid hemorrhage could occur in contusions with trauma.
psychiatric manifestations, worsening with repeated concus-
sions. There are no radiologic or pathologic findings. Arteri- PBD9 1262 BP9 821–822 PBD8 1289–1290 BP8 870–871
olosclerosis is typically seen with hypertension. Hemorrhage
following the traumatic event could organize to obstruct CSF 18 D Tearing of bridging veins leads to an acute subdural
flow or absorption, but this would have been identified with hematoma; this almost always results from head trauma in
the original CT scan. The term leukoencephalopathy applies which there has been a fall, which may have been minor and
C H A P T E R 2 8 Central Nervous System 4 4 7
gone unnoticed. The risk of hemorrhage is greater in elderly sudden localizing signs. A subdural hematoma, which most
individuals because of cerebral atrophy, which leaves the frequently results from head trauma sustained in a fall, is
bridging veins beneath the dura at the vertex more vulner- unlikely to develop in a few minutes and would not explain
able to traumatic tearing. Arteriovenous (vascular) mal- the TIAs.
formations are often located within the parenchyma of a
hemisphere, and bleeding from them occurs more often in PBD9 1264–1267 BP9 814–815 PBD8 1291–1293 BP8 863
young adults. When saccular (berry) aneurysms rupture,
the bleeding is typically subarachnoid and at the base of 22 D The neurons that are most sensitive to anoxia reside
the brain. A tear of the middle meningeal artery can occur in the hippocampus, along with the cerebellar Purkinje cells
in head trauma (e.g., a blow to the head), but it results in and the larger neocortical neurons. In addition, the first areas
an acute epidural hematoma. Thrombosis of an intracranial in the neocortex to be affected are the “watershed” areas
artery may result in an infarction, which can be hemor- between the three major cerebral circulations, including the
rhagic, but the hemorrhage typically does not extend into watershed located superiorly between the anterior cerebral
subarachnoid or subdural locations. and middle cerebral circulations, as in this study. “Red”
shrunken neurons, especially in the areas mentioned, are
PBD9 1262 BP9 821–822 PBD8 1289–1290 BP8 870–871 typically seen in the early stages of global hypoxia, as may
occur in a severe hypotensive episode. Focal hypoxia leads
1 9 C Global cerebral ischemia has occurred in this man, to infarcts. Autoimmunity can lead to vasculitis and subse-
leading to brain death. There is ongoing liquefactive necro- quent hypoxemia. Chemotherapy tends to damage actively
sis, and in 2 to 3 weeks there will be numerous macrophages dividing cells more severely. Diabetes mellitus causes ath-
that phagocytize the cellular debris. These macrophages erosclerosis, which can lead to hypoxemia. Lead poisoning
can persist for months. The neocortex has more vulnerable leads to encephalopathy, not ischemia. Poor nutrition with
pyramidal cell layers with a pattern of pseudolaminar necro- a deficiency of thiamine (vitamin B1) can lead to Wernicke
sis. Fibroblastic proliferation with collagen deposition is disease, which affects the mammillary bodies and periaque-
uncommon in the CNS, except around organizing abscesses. ductal gray matter most severely.
An abscess is where neutrophils would be found, as well
as meninges with acute meningitis. Inflammation of brain PBD9 1264–1267 BP9 814–815 PBD8 1291–1292 BP8 863–865
parenchyma is most often lymphocytic. Oligodendrocytes
provide myelination to axons. Dying red neurons are seen 2 3 E An acute cerebral infarction results from obstruction
after 12 hours following ischemic injury and may persist for of blood flow causing focal cerebral ischemia. After 2 days,
days, but not weeks. there would be some cerebral softening and edema with
ischemia of neurons, but little else. Hypercholesterolemia is
PBD9 1263–1265 BP9 814–815 PBD8 1291–1292 BP8 863–864 a risk factor for atherosclerosis, which is the major cause of
thrombotic cerebral arterial occlusions. The antiphospholipid
2 0 B This cerebral infarction is a large hemorrhagic and syndrome can produce thrombotic and embolic disease, but
softened area of beginning liquefactive necrosis after vascu- an embolic “stroke” is typically hemorrhagic, and antiphos-
lar injury in the distribution of the middle cerebral artery. pholipid syndrome is uncommon at this age. A positive
Emboli likely emanate from the heart. It takes weeks to blood culture suggests sepsis with the possibility of meningi-
months for macrophages to clear the debris of liquefactive tis or cerebral abscess formation, but abscesses typically have
necrosis and leave a cystic space. A vascular malformation ring enhancement on CT scans. Elevated serum levels of very
has irregular vascular channels that give a mass effect with long chain fatty acids are present in patients with adrenoleu-
a dark red-to-bluish appearance. Metastases may be solitary kodystrophy, a rare disorder that leads to myelin loss at an
masses but are most often multiple, and may have central early age. Hyperammonemia occurs in hepatic encephalopa-
hemorrhage or necrosis, but are often multiple. An orga- thy with liver failure; it produces Alzheimer type II gliosis,
nizing subdural hematoma would leave a uniform area of but no focal or gross lesions. Neurosyphilis is now rare; it
compression with flattening of the underlying hemisphere. does not produce focal ischemic lesions.
A contusion could produce some minimal focal loss of cortex
with brown hemosiderin staining. PBD9 1265–1267 BP9 815–816 PBD8 1292–1295 BP8 863–865
PBD9 1264–1267 BP9 814–816 PBD8 1293–1295 BP8 863–865 2 4 E A remote cerebral infarction is present. Thrombo-
embolic disease with cerebral infarction most often results
2 1 B The brief episodes of neurologic dysfunction repre- from a cardiac disease (e.g., endocarditis, mural thrombo-
sent transient ischemic attacks (TIAs) and are a prodrome sis, prosthetic valvular thrombosis). Hemorrhagic infarcts
to stroke in many cases. Atherosclerotic cerebrovascular are more likely to occur when emboli partially occlude a
disease is a common antecedent to cerebral infarction, and vessel or undergo dissolution. Thrombosis over atheroscle-
metabolic syndrome with dyslipidemia and hyperglycemia rotic lesions is more likely to cause nonhemorrhagic infarcts.
is a risk factor. A vascular malformation most often produces AIDS is not often associated with significant cardiovascular
symptoms caused by bleeding in young adults. A neoplasm or cerebrovascular diseases. Head trauma with hemorrhage
is unlikely to produce such sudden, episodic symptoms and is more common in individuals with chronic alcoholism.
signs. Meningoencephalitis may produce general features Hypertension is most often associated with basal ganglia,
such as fever, headache, confusion, and seizures, but not pontine, and cerebellar hemorrhages and with small lacunar
4 4 8 U N I T I I Diseases of Organ Systems
infarcts. Malignant neoplasms may be associated with para- mimics Alzheimer disease (AD), with progressive cognitive
neoplastic syndromes, including hypercoagulability and decline, and a parkinsonian movement disorder is often pres-
thrombosis, but this is much less common than heart disease ent. Neuritic plaques and neurofibrillary tangles are charac-
as a cause for cerebrovascular disease and stroke. teristic for AD, which has progressive cognitive decline. Pick
bodies are seen with Pick disease, which is similar to AD.
PBD9 1265–1267 BP9 815–816 PBD8 1293 BP8 864–865 Plaques of white matter demyelination are seen with multi-
ple sclerosis, and the gray matter is relatively spared, so that
2 5 D Primary angiitis of the CNS is uncommon. It severe cognitive impairment is not a usual feature.
involves small peripheral vessels. The cause is unknown, but
it appears to be immunologically mediated, so immunosup- PBD9 1268 BP9 836 PBD8 1295, 1319 BP8 891
pressive therapy is of benefit, such as cyclophosphamide and
methylprednisolone. Infections are unlikely to produce such 29 A Alzheimer disease (AD) can be complicated by cere-
focal involvement of small vessels. Hypertensive encepha- bral amyloid angiopathy and terminal hemorrhagic stroke.
lopathy produces fibrinoid necrosis of arterioles. NSAIDs Formation and aggregation of the Aβ peptide is now consid-
or aspirin as anti-inflammatory or anti-pyretic agents are ered central to the pathogenesis of AD. Aβ peptide is derived
not strong enough to address the inflammatory process in from abnormal processing of amyloid precursor protein
this case. Mannitol infusion is used to treat marked cerebral (APP). When APP, a transmembrane protein, is cleaved by
edema, but that is not the major finding in this case. α-secretase within the Aβ sequence, followed by γ-secretases,
a soluble nontoxic fragment is formed. Cleavage of the Aβ
PBD9 1266 BP9 819 PBD8 1293 BP8 868 sequence by β-secretase and then γ-secretase gives rise to
Aβ peptides that aggregate and form the amyloid cores that
2 6 D Hypertensive hemorrhages are most likely to arise elicit a microglial and astrocytic response to form neuritic
in the basal ganglia (shown in the figure), thalamus, cerebral plaques. Conformational change in prion protein leads to
white matter, pons, or cerebellum. Multiple hemorrhages Creutzfeldt-Jakob disease, a rapidly progressive dementia
are uncommon. The small vessels weakened by hyaline with spongiform encephalopathy but not neuritic plaques
arteriolosclerosis are prone to rupture. Chronic alcoholism or amyloid deposition. Loss of dopaminergic neurons with
predisposes to falls with subdural hematomas or contusions. deficiency of dopamine is central to the pathogenesis of Par-
Metastases are typically multiple and peripheral at the gray- kinson disease. Expansion of polyglutamine repeats owing
white junction. The plaques of multiple sclerosis occur in to CAG trinucleotide repeat-expansion underlies Hunting-
white matter and do not bleed. Thromboemboli can produce ton disease. Although abnormally phosphorylated forms of
ischemic cerebral infarctions, sometimes with hemorrhage, tau protein are found in neurofibrillary tangles seen in AD,
and they usually involve the cerebral cortex. there is no mutation of the tau gene, and the tangles are not
considered primary in the pathogenesis of AD. Mutation of
PBD9 1267–1268 BP9 819 PBD8 1295–1296 BP8 868 the tau gene can be found in frontotemporal lobe dementias.
2 7 A He developed acute hypertensive encephalopathy PBD9 1269 BP9 817 PBD8 1313–1317 BP8 891–893
from the rapid and marked increase in blood pressure. There
is extensive cerebral edema with increased intracranial pres- 3 0 D About 1 in 50 individuals has a saccular (berry)
sure, but no localizing signs. The arterioles are involved, and aneurysm. Although this lesion is present at birth as a con-
like malignant hypertension involving the kidney, there is genital defect in the arterial media at intracerebral arterial
fibrinoid necrosis and petechial hemorrhages. Telangiecta- branch points, it can manifest later in life with aneurysmal
sias may be one form of vascular malformation, typically a dilation and possible rupture. These aneurysms are the most
localized lesion not related to hypertension. Lacunar infarcts common cause of spontaneous subarachnoid hemorrhage in
develop with hypertension, but they tend to be small and adults. The bleeding from amyloid angiopathy is in periph-
are often silent, but may cause significant neurologic impair- eral cortex, and most likely to occur in association with
ment, though more likely a focal deficit due to focal involve- Alzheimer disease. A hypertensive hemorrhage from arte-
ment. Hypertensive hemorrhages may be large, and the riolosclerosis tends to remain within the brain parenchyma.
basal ganglia region is a common location, but such a lesion Thromboemboli can cause infarctions, most often in the dis-
could produce a unilateral mass effect with papilledema on tribution of the middle cerebral artery in cortex, and embolic
one side. Subarachnoid hemorrhages are more likely to occur infarcts can be hemorrhagic, but the blood typically does not
from ruptured saccular aneurysms. reach the CSF. A subdural hematoma over the brain surface
results from a tear of bridging veins.
PBD9 1268 BP9 819 PBD8 1295 BP8 868
PBD9 1269–1271 BP9 817–818 PBD8 1297–1298 BP8 866–867
2 8 A This patient’s stepwise loss of cognitive function is
consistent with vascular dementia, and his history of diabe- 31 D Intracranial aneurysms are typically saccular and
tes mellitus makes underlying heart disease with embolic enlarge slowly over time. Aneurysms that grow to 4 to 7 mm
events, or vascular disease involving the brain, more likely. are at the greatest risk of rupture. Rupture occurs into the sub-
Some cases have diffuse cortical laminar necrosis from global arachnoid space at the base of the brain, where the cerebral
hypoxic events, whereas others have multiple lacunar infarcts, arterial distribution originates around the circle of Willis, and
and still others have embolic infarcts. Lewy body dementia where saccular aneurysms are most likely to arise. Neither a
C H A P T E R 2 8 Central Nervous System 4 4 9
berry aneurysm nor the bleeding that results is likely to cause 3 5 C The most common etiologic organism for acute
a mass effect and herniation. In some cases of survival after bacterial meningitis in his age group, because of vaccina-
rupture of a berry aneurysm, a noncommunicating hydroceph- tions, is now Streptococcus pneumoniae, a gram-positive
alus results from organization of the subarachnoid hemor- coccus. Pneumococci also are likely to be seen in an adult.
rhage occluding foramina of Luschka and Magendie. Epidural The number of CNS infections with Haemophilus influenzae,
hematomas arise from a tear of the middle meningeal artery, a gram-negative bacillus, in this age group has decreased
typically as a result of head trauma. Trauma also can cause a because of widespread immunization. The gram-negative
tear of bridging veins that produces a subdural hematoma. diplococci of Neisseria meningitidis are seen in young adults.
The gram-negative bacilli of Escherichia coli are most often
PBD9 1269–1271 BP9 817–818 PBD8 1297–1298 BP8 866–867 seen in neonates. The short, gram-positive rods of Listeria
monocytogenes appear sporadically or in epidemics caused
32 B Arteriovenous (vascular) malformations most often by food contamination. With these clinical and CSF features,
occur in the cerebral hemisphere of a young adult and can it would be unusual if bacteria were not present in the CSF.
often be completely resected without complication. There may
be slow leakage of blood from the lesion over time, resulting PBD9 1272 BP9 825 PBD8 1299–1300 BP8 874–875
in the clinical symptoms and the gliosis seen on biopsy in this
case. An angiosarcoma with malignant-appearing cells is not 36 A A cerebral abscess is most often a complication of
a primary lesion in the brain parenchyma. A plaque of demy- an infection, such as pneumonia or endocarditis, with onset
elination in multiple sclerosis can appear as a mass, but its days to weeks earlier. The bacteria spread hematogenously.
features include loss of myelin with gliosis and macrophages, As the abscess organizes, it is ringed by fibroblasts that
not vascular abnormalities. An abscess would have an orga- deposit collagen; this feature is characteristic of an abscess
nizing wall with collagen and gliosis, but no prominent larger in the CNS. A neoplasm occasionally may be ring enhancing,
vessels. Head trauma generally produces contusions and but a glioblastoma is an aggressive malignancy that is not
hematomas on the surface, but not hemorrhages in the brain well demarcated. Metastases are mass lesions that are typi-
parenchyma. A ruptured aneurysm can extend upward into cally multifocal. A multiple sclerosis plaque is generally not
the parenchyma in some cases; the outcome is always fatal large, is found in white matter, and does not typically have
with this complication. ring enhancement. An infarct would produce sudden signs
and symptoms that improve over time, and the CSF protein
PBD9 1271 BP9 818–819 PBD8 1298–1299 BP8 867–868 would not be increased.
3 3 C Acute meningitis, with a purulent exudate on the PBD9 1273–1274 BP9 826 PBD8 1300 BP8 876
cerebral convexities shown in the figure, is indicative of
bacterial infection. At his age, a common etiologic agent is 3 7 B Acute otitis media may be complicated by spread of
Neisseria meningitidis, initially presenting as pharyngitis, the infection to the mastoid air cells, and then to skull bone,
and untreated proceeding to Waterhouse-Friderichsen syn- and then to the epidural space. This also may be termed
drome with disseminated intravascular coagulopathy. Cryp- pachymeningitis or epidural empyema. Spread to the underly-
tococcosis should be considered in immunocompromised ing meninges may next occur. Encephalitis involves the sub-
patients, but some cases occur in immunocompetent patients; stance of the brain. Multicystic encephalopathy is a severe
a meningoencephalitis can occur. Tuberculous meningitis complication of perinatal brain injury with infarction. Sub-
does not manifest so acutely, and the exudate is typically on dural hematomas are most often caused by trauma. The tri-
the base of the brain. Poliomyelitis could occur after pharyn- geminal nerve is located at a distance from the mastoid air
gitis, but onset is insidious, with increasing paralysis from cells so that it is unlikely to be involved; but the facial nerve
loss of motor neurons. It does not cause meningitis. Cerebral adjacent to the ear may be involved.
toxoplasmosis may occur in immunocompromised patients,
but the lesions are parenchymal abscesses, not meningitis. PBD9 1274 BP9 824–825 PBD8 1301 BP8 876
PBD9 1272 BP9 825 PBD8 1299–1300 BP8 874–875 3 8 C Tuberculous meningitis is a complication of dis-
seminated tuberculosis, and young children are at increased
3 4 D Headache, fever, pronounced neutrophilia, a high risk in locations where tuberculosis is prevalent. It tends to
CSF protein level, and a low glucose concentration all point produce a more chronic course. Cranial nerves, such as the
to bacterial meningitis. Staphylococcus aureus is a common abducens in this case, can be involved. A large granuloma-
infection among injection drug users. Herpes simplex virus tous mass, a tuberculoma, may complicate some cases. Viral
produces encephalitis, not meningitis. Tuberculous meningi- “aseptic” meningitis is marked by mononuclear cells, but
tis has a more insidious onset. This patient does not have a the protein is not usually markedly elevated, and no mass
mass lesion of toxoplasmosis or focal lesions of progressive develops. Bacterial meningitis is often associated with a low
multifocal leukoencephalopathy (PML) that may be associ- glucose, but not a mass, and the inflammatory response is
ated with AIDS. PML is associated with the JC polyomavirus. predominantly polymorphonuclear. T. pallidum is the caus-
Toxoplasmosis, which may occur in immunocompromised ative agent for neurosyphilis with a long, insidious course
patients, produces parenchymal abscesses, not meningitis. and no mass effect. T. solium can lead to cysticercosis, with
cystic masses in the brain.
PBD9 1272 BP9 825 PBD8 1299–1300 BP8 874–875
PBD9 1274 BP9 826 PBD8 1301 BP8 874–875
4 5 0 U N I T I I Diseases of Organ Systems
3 9 F He has neurosyphilis from infection by Treponema pal- then recovery, then the late post-polio syndrome. This
lidum. This form of tertiary syphilis occurs years following pri- enterovirus attacks lower motor neurons, leading to neuro-
mary infection. His eye finding is consistent with Argyll Rob- genic muscle weakness and atrophy. The anterior horns of
ertson pupil; his positive Romberg test is the result of tabes the spinal cord include lower motor neurons. Cranial nerve
dorsalis. His mentation has changed from general paresis. Lis- nuclei with lower motor neurons may also be involved. The
teriosis and streptococcal infections are most likely to produce basal ganglia modulate muscle movement, and involvement
an acute meningitis. Rabies may have an incubation period of of these structures may result in movement disorders, but
1 to 3 months, but then manifests with an acute severe enceph- not paralysis. The corticospinal tracts are axons from upper
alitis. Rubeola (measles) infection rarely leads to subacute motor neurons found in the neocortex, and neither is involved
sclerosing panencephalitis years later, marked by spasticity with polio. The dorsal root ganglia are involved with sensory
and seizures. Toxoplasmosis is an opportunistic infection with pathways. Myoneural junctions may be involved with myas-
encephalitis and abscess developing over weeks. thenia gravis or clostridial infections (botulism, tetanus).
PBD9 1274–1275 BP9 826 PBD8 1301–1302 BP8 875 PBD9 356, 1277 BP9 828 BPD8 350–351, 1304 BP8 878
40 B An acute lymphocytic meningitis is most typically 4 4 B The child had rabies, an infectious disease in which
caused by a virus, such as West Nile virus, an equine enceph- the virus travels from the site of an infected animal bite
alitis virus, or an echovirus. It is sometimes referred to as up nerves to the CNS. Pathognomonic Negri bodies are
aseptic meningitis because routine Gram staining and bacte- cytoplasmic inclusions found in the hippocampal pyra-
rial cultures are negative. Most cases are self-limited, occur midal cells and cerebellar Purkinje cells. Worldwide,
in immunocompetent individuals, and resolve without sig- unvaccinated dogs remain the most common vector for
nificant sequelae. Cryptococcal and toxoplasmal infections transmission of this bullet-shaped virus to man. The sus-
can occur in immunocompromised patients, but the India pected animal must be sacrificed to identify the virus in
ink test would be positive in the former, and CT scan would the brain. Infected neurons generally do not undergo cell
show focal ring-enhancing lesions in the latter. Listerial and death; instead the virus induces neurotoxin production
meningococcal infections are seen sporadically and have a that affects surface receptor interaction with neurotrans-
neutrophilic response. mitters. After symptoms develop, survival is rare. Multinu-
cleated cells may be seen in microglial nodules associated
PBD9 356, 1275 BP9 826–827 PBD8 351, 1302 BP8 874 with HIV infection. Perivascular lymphocytic infiltrates are
often seen with a variety of viruses, such as arboviruses or
4 1 C Hemorrhagic lesions of the temporal lobes are char- echoviruses, causing encephalitis. Toxoplasma gondii infec-
acteristic of herpes simplex virus encephalitis; cases are few tion is characterized by finding enlarged, infected cells
and usually sporadic, occurring in apparently healthy indi- filled with bradyzoites. Spongiform change is characteris-
viduals. The lesions of aspergillosis can be hemorrhagic, but tic for prion disease.
they are typically seen in immunocompromised individuals.
Cytomegalovirus infection occurs in neonates and in immu- PBD9 1277–1278 BP9 828 PBD8 1304–1305 BP8 878
nocompromised adults, but it does not produce hemorrhagic
lesions. Arboviral infections produce focal lesions that may 4 5 B AIDS dementia complex occurs late in the course of
have an associated vasculitis with hemorrhage, but the CSF HIV infection. HIV-1 produces an encephalitis characterized
protein is usually elevated, and there is a neutrophilic pleo- by a collection of reactive microglial cells (microglial nodules).
cytosis. Meningococcal infections produce meningitis. HIV-1-infected mononuclear cells, particularly macrophages,
can fuse to form multinucleate cells, which are seen within
PBD9 1275–1276 BP9 827–828 PBD8 1302–1303 BP8 876–877 microglial nodules. Spongiform change suggests Creutzfeldt-
Jakob disease, a rapidly progressive dementia unrelated to
4 2 A Cytomegalovirus (CMV) infection is one of the con- HIV infection. Lacunar infarcts are small, cavitary infarcts
genital TORCH infections, and it can become widely dis- that result from arteriolosclerosis of the deep penetrating
seminated to affect the CNS. Periventricular leukomalacia arteries and arterioles. Such arteriolar lesions occur in indi-
is characteristic of CMV infection. Group B Streptococcus viduals with long-standing hypertension and are unlikely to
infections cause premature rupture of membranes and sep- be found in a 37-year-old man. Neocortical neuritic plaques
sis without significant CNS findings. Heart failure in utero and neurofibrillary tangles are typical of Alzheimer disease
causes hydrops fetalis. Herpes simplex virus infection and are unlikely to manifest at this patient’s age. Plaques of
of neonates typically occurs during passage through the demyelination are typical of multiple sclerosis.
infected birth canal, not in utero. HIV infection produces no
significant CNS findings in the perinatal period. Listeriosis PBD9 1278 BP9 828 PBD8 1305 BP8 877–878
can produce focal microabscesses in various organs, but usu-
ally there is minimal necrosis. 4 6 C Progressive multifocal leukoencephalopathy is
caused by the JC polyomavirus and occurs in immunocom-
PBD9 359–360, 1277 BP9 828 PBD8 353–355, 1304 BP8 877 promised individuals, including individuals with AIDS. The
patient was treated for chronic myelogenous leukemia. Cyto-
43 A Poliomyelitis is described, starting with the minor megalovirus infection also complicates the course of immu-
gastrointestinal illness, followed by the acute major illness, nocompromised patients, but it causes large intranuclear
C H A P T E R 2 8 Central Nervous System 4 5 1
inclusions, most often in endothelial cells. Herpes simplex solitary mass. Metastatic carcinoma, which typically pres-
virus is uncommon, even in immunocompromised patients, ents with multiple lesions, is uncommon at this age. A spon-
and it most often produces hemorrhagic encephalitis in tem- giform encephalopathy, such as Creutzfeldt-Jakob disease,
poral lobes. Rabies virus produces CNS excitability with typically has no grossly visible or radiographic findings.
convulsions, meningismus, and hydrophobia. Subacute
sclerosing panencephalitis is a rare complication of measles PBD9 1279–1280 BP9 829–830 PBD8 1306–1307 BP8 880
(rubeola) virus infection and leads to progressive mental
decline, spasticity, and seizures. West Nile virus, similar to 50 E A rapidly progressive dementia is most consistent
many arboviruses, can cause a meningoencephalitis. with Creutzfeldt-Jakob disease (CJD). CJD is one of a group
of diseases that are called spongiform encephalopathies because
PBD9 1278–1279 BP9 828–829 PBD8 1305–1306 BP8 878–879 they produce a microscopic vacuolated appearance of the neo-
cortex. CJD occurs in sporadic or familial forms and is caused
47 D Cryptococcal meningoencephalitis is a complication by prion protein. The normal prion protein of the brain, desig-
of his immunocompromised state. Cryptococcus neoformans nated PrPc, can undergo conformational change to PrPsc, which
typically has a thick capsule, making it easily visible with then induces further change in PrPc to PrPsc. This patient’s age
the India ink preparation, a procedure that can be performed and clinical findings are characteristic of the sporadic type of
within a few minutes on a CSF sample. A cryptococcal anti- CJD, which may arise from spontaneous mutation or from
gen test on the CSF would also be useful for this patient. Brain exposure to PrPsc. Variant CJD, which may be linked to expo-
biopsies are not commonly performed, and other, less inva- sure to bovine spongiform encephalopathy, occurs in much
sive methods should be pursued first. Bacterial meningitis is younger patients and does not produce the characteristic EEG
possible, and pneumococcus would be a common bacterial findings. Microglial nodules may be seen in patients with
cause, but this description is consistent with cryptococcosis. AIDS. Neuritic plaques are seen in Alzheimer disease, which
Of the remaining fungal organisms listed, none are readily occurs over many years. The demyelinating plaques of mul-
identified with India ink. Aspergillus spp. appear as branch- tiple sclerosis develop over years, as do the Lewy bodies of
ing septate hyphae, not as yeasts. Blastomyces dermatitidis is Parkinson disease and diffuse Lewy body disease.
characterized by broad-based budding yeasts. Coccidioides
immitis yeast forms appear as large spherules containing PBD9 1281–1283 BP9 831–832 PBD8 1309–1310 BP8 880–881
endospores. Histoplasma capsulatum organisms are small and
tend to be found within macrophages. 51 F Multiple sclerosis (MS) produces white matter
plaques of demyelination, and most patients develop optic
PBD9 1279–1280 BP9 503, 829 PBD8 384 BP8 324, 879 neuritis with visual difficulties, often unilateral. The course
of MS varies, with many relapses and remissions, and some
48 D Cysticercosis from eating uncooked pork can result patients are affected more severely than others. Some patients
in the release of larvae that penetrate the gut wall and dis- have minimal problems, but most can be expected to have
seminate hematogenously, often settling in gray and white further neurologic problems. Severe neurologic impairment
cerebral tissue, where they develop into cysts. The cysts may and death are unlikely, and most patients live for decades.
cause obstructive hydrocephalus. Neurocysticercosis is a There is no defined inheritance pattern. Although MS is an
major cause for seizures in parts of the world where pork immunologically mediated disease, immune dysregulation
tapeworms are ingested. Aspergillosis is a fungal disease leading to development of lymphoid neoplasms is unlikely
in which the foci of inflammation grossly resemble granu- to occur. The focality of white matter lesions and the spar-
lomas, but there is often minimal inflammatory response, ing of gray matter make dementia and quadriplegia unlikely
and the propensity for vascular invasion often produces a complications of MS. Seizure disorders in MS are uncom-
hemorrhagic border to the lesions. Cryptococcosis most mon. Tremor at rest is a feature of Parkinson disease.
often involves the lungs and meninges. Malaria caused by
Plasmodium falciparum produces hemolytic anemia, spleno- PBD9 1283–1285 BP9 832–834 PBD8 1310–1312 BP8 887–890
megaly, and cerebral thrombosis. Toxoplasmosis can be a
congenital infection. In immunocompromised adults, it can 52 D This shifting spectrum of clinical findings over time
produce inflammation in multiple tissues, but most often it in a young adult suggests the diagnosis of multiple sclerosis.
causes chronic abscessing inflammation in the brain. African The plaques of demyelination that give rise to the differing
trypanosomiasis produces sleeping sickness. symptoms can be found in various locations, but they most
often occur in periventricular white matter. CSF immuno-
PBD9 395–396, 1279 PBD8 392–393, 1306 globulins are increased, and most patients show oligoclo-
nal bands of IgG. Neurosyphilis, a form of tertiary syphilis,
49 E Toxoplasmosis is a common opportunistic infec- is rare at this age and probably would not cause localizing
tion that affects the CNS in immunocompromised patients, signs that change. Cryptococcal meningitis would manifest
including those with AIDS, and produces abscesses that more acutely with meningeal signs. Primary or malignant
organize on the periphery to produce a bright ring on CT brain tumors are uncommon at this age and would not have
and MRI. Candida fungal infections of the CNS are rare, and such a long course without serious sequelae. Xanthochromia
disseminated candidiasis in AIDS is uncommon. Malignant from hemorrhage would suggest a more acute problem.
lymphomas also can produce this picture, but without fever,
and they generally occur as fewer, larger masses or as a PBD9 1283–1285 BP9 832–834 PBD8 1310–1312 BP8 887–889
4 5 2 U N I T I I Diseases of Organ Systems
5 3 A The rapid correction of hyponatremia is a common and more behavioral changes. The “knifelike” gyral atrophy
antecedent to central pontine myelinolysis, with demyelin- of frontal and temporal lobes and relative sparing of parietal
ation in the basis pontis, with the round area of decreased and occipital lobes are characteristic of Pick disease. Pick
signal intensity shown in the figure. Extrapontine myelin- bodies with tau protein are seen in remaining neurons, but
olysis may also occur. A history of alcohol abuse increases the neuritic plaques and neurofibrillary tangles seen in AD
the risk. Cerebral edema sufficient to produce herniation are not increased. Huntington disease affects mainly the cau-
would cause papilledema, not noted in this case. Intracranial date nuclei and basal ganglia; onset occurs in middle age,
hemorrhages would not result from electrolyte and fluid dis- and choreiform movements are common. Leigh disease is a
turbances. A subacute combined degeneration of the spinal mitochondrial encephalomyopathy that can cause muscular
cord occurs slowly as a consequence of vitamin B12 (cobala- weakness and neurologic deterioration beginning at a young
min) deficiency. Wernicke-Korsakoff syndrome is now a rare age. Multiple system atrophy (MSA) has features that over-
accompaniment to chronic alcoholism that affects mammil- lap those of striatonigral degeneration, olivopontocerebel-
lary bodies and periaqueductal gray matter. lar atrophy, and Shy-Drager syndrome; most patients with
MSA exhibit symptoms similar to those of Parkinson disease.
PBD9 1286 BP9 834 PBD8 1313 BP8 889 MSA is characterized microscopically by the appearance of
glial cytoplasmic inclusions. In Parkinson disease, loss of pig-
5 4 B Acute disseminated encephalomyelitis is an immu- mented neurons in the substantia nigra leads to movement
nologically mediated demyelinating disease that has some problems. Vascular dementia, or multi-infarct dementia, can
features similar to multiple sclerosis, but may occur in have clinical features that mimic those of AD, but there are
younger patients, have an abrupt onset, and be rapidly fatal. multiple small infarcts that collectively produce dementia,
Most cases are preceded by an infection. The remaining and the neurologic decline occurs in a stepwise fashion.
choices are unlikely to have bilateral optic neuritis. Abscesses
are likely to be bacterial in origin. Emboli are uncommon in PBD9 1292–1294 BP9 838 PBD8 1318 BP8 891
children, and likely to produce infarctions. Metastases are
unlikely in children. Thiamine deficiency may lead to Wer- 58 A Dementia with Lewy bodies (DLB) combines clinical
nicke disease, which has hemorrhagic lesions and is unre- features of Alzheimer disease (AD) and idiopathic Parkin-
lated to infection. Vasculitis may produce focal lesions but is son disease. Mutations in the gene for α-synuclein have been
uncommon in children. linked to idiopathic Parkinson disease, and Lewy bodies can
be found in the substantia nigra neurons, but the clinical
PBD9 1286 BP9 834 PBD8 1312–1313 BP8 889 dementia and cortical Lewy bodies point to DLB. Amyloid
precursor protein (APP) is encoded by a gene on chromo-
5 5 D The figure shows a neuritic plaque with a rim of dys- some 21 (perhaps explaining early AD in trisomy 21) and is
trophic neurites surrounding an amyloid core consistent with processed to form the Aβ amyloid of neuritic plaques in AD.
Alzheimer disease (AD), the most common form of progres- The e4 allele of apolipoprotein E can bind Aβ and increase
sive dementia. AD is marked by increased numbers of micro- the risk of AD. Huntingtin is the protein product of the HD
scopic neuritic plaques and neurofibrillary tangles compared gene in Huntington disease. Presenilin 1 and 2 mutations can
to controls for age. Choreiform movements suggest Hunting- increase production of Aβ and increase the risk of early-onset
ton disease. Gait disturbances occur in Parkinson disease. Sei- AD. Tau protein is found in neurofibrillary tangles of AD
zures are associated with many lesions, but often a pathologic and in Pick bodies of Pick disease.
finding is not discernible. Symmetric muscular weakness sug-
gests amyotrophic lateral sclerosis. PBD9 1295–1296 BP9 840 PBD8 1321–1322 BP8 891, 895
PBD9 1290–1291 BP9 837–838 PBD8 1314–1316 BP8 891–893 59 E Loss of pigmented dopaminergic neurons in the sub-
stantia nigra of the midbrain is most characteristic of Parkinson
56 E The clinical history of dementia and the presence of disease. Pill-rolling tremors at rest are typical of this disorder.
numerous neuritic plaques and amyloid deposition in blood A variety of genetic abnormalities have been associated with
vessel walls are characteristic of Alzheimer disease (AD). The forms of Parkinson disease, including α-synuclein, parkin, DJ-1,
e4 allele of the ApoE4 gene increases the risk of developing and PINK1 gene mutations and mitochondrial dysfunction.
AD by unknown mechanisms. Expansion of CAG repeats on Ataxia suggests a disruption in the motor control pathways,
chromosome 4p16 causes Huntington disease. There is no such as the cerebellum, or proprioception, from dorsal spinal
association between HLA genes and AD. Increased repeats cord columns. Choreiform movements suggest Huntington
in the FMR1 gene occur with fragile X syndrome. Mutant disease, which affects the caudate, not the substantia nigra.
prion genes give rise to spongiform encephalopathies, such Short-term memory problems suggest hippocampal lesions.
as Creutzfeldt-Jakob disease. Symmetric weakness suggests a motor neuron disease.
PBD9 1286–1292 BP9 836–838 PBD8 1313–1317 BP8 891–893 PBD9 1294–1295 BP9 839–840 PBD8 1319–1321 BP8 893–895
5 7 F Pick disease is the best known form of frontotemporal 6 0 D Huntington disease is a progressive degenerative
lobar degeneration with tau-containing inclusions (FTLD-tau) disorder that affects basal ganglia, including the putamen
and has clinical features similar to the features of Alzheimer and caudate nucleus through loss of spiny striatal neurons
disease (AD), but initially FTLD-tau causes less memory loss that normally dampen motor activity. This disease, inherited
C H A P T E R 2 8 Central Nervous System 4 5 3
in an autosomal dominant pattern, is caused by an abnor- of metabolism involving lysosomal (arylsulfatase A in this
mal expansion of the trinucleotide CAG in the huntingtin case) or peroxisomal enzymes that affect white matter exten-
gene on chromosome 4, which normally has 6 to 35 CAG sively and cause myelin loss and abnormal accumulations of
copies. There may be 40 to 55 copies in patients with typical myelin from failure of generation, maintenance, or catabo-
Huntington disease and 70 repeats in patients with earlier lism of myelin. There are no discrete plaques of demyelin-
onset of the disease. A “premutation” with 36 to 39 repeats ation, however, in contrast to multiple sclerosis. Sparing of
may have reduced penetrance. These patients have atrophy, subcortical myelin (U fiber) is often seen in leukodystrophies.
with loss of neurons and gliosis starting in the caudate, as Acute disseminated encephalomyelitis is a postinfectious
well as putamen and globus pallidus. About 10% of cases of process with abrupt onset. Progressive multifocal leukoen-
Creutzfeldt-Jakob disease are genetically determined, with cephalopathy is an infectious lesion that occurs in immuno-
the inheritance of an abnormal prion protein that leads to compromised adults. Tay-Sachs disease affects infants.
spongiform encephalopathy in later adult life. Tay-Sachs dis-
ease of infancy and childhood is caused by a deficiency of PBD9 1302–1303 BP9 834 PBD8 1326–1327 BP8 889
hexosaminidase A. Trisomy 21 results in mental retardation
present at birth. Mutations in presenilin genes cause famil- 6 4 E Wernicke disease results from a deficiency of vitamin
ial Alzheimer disease (AD). The risk of AD increases with B1 (thiamine). Wernicke disease is uncommon in individu-
increased levels of apolipoprotein E. als who have a varied diet, but individuals with a history of
chronic alcoholism may not. Capillary proliferation, hemor-
PBD9 1297–1298 BP9 840 PBD8 1322–1323 BP8 895–896 rhage, necrosis, and hemosiderin deposition are often found
in the mammillary bodies and the periaqueductal gray mat-
6 1 D She had Friedreich ataxia, an autosomal recessive ter, resulting in paralysis of the extraocular muscles. If mem-
progressive illness that most often has an onset in the ory problems with confabulation are observed, the thalamus
first decade of life. The frataxin gene encodes for a protein is involved and the diagnosis is Wernicke-Korsakoff syn-
involved in iron regulation in cells, and a GAA trinucleotide drome. Though deficiency of either B12 or folate may produce
repeat expansion results in decreased protein and decreased macrocytic anemia, subacute combined degeneration of the
mitochondrial oxidative phosphorylation. The other options spinal cord is seen with vitamin B12 (cobalamin) deficiency,
listed have no cardiac involvement. Mutations of the hunting- but folate deficiency does not produce CNS signs. Dementia
tin gene are seen with Huntington disease marked by choreo- may be present in individuals with niacin deficiency. A defi-
athetosis beginning in young to middle-aged adults. Increased ciency of pyridoxine may result in a peripheral neuropathy.
tandem repeats in the FMR1 gene account for cases of fragile
X syndrome characterized by mental retardation. The dystro- PBD9 433, 1304 BP9 835 PBD8 427, 1328 BP8 890
phila myotonia–protein kinase gene is abnormal in cases of
myotonic dystrophy with muscular weakness and dementia. 6 5 A Liver failure with hepatic encephalopathy can occur
in severe liver disease from various causes, including com-
PBD9 1299 BP9 841 PBD8 1323 monly chronic alcoholism. Hyperammonemia is a feature
of liver failure. Carbon monoxide poisoning can produce
62 B The progressive and symmetric nature of this obtundation and coma. Severe hypoglycemia can damage
patient’s disease is a classic feature of amyotrophic lateral neurons in the hippocampus and neocortex. An elevated
sclerosis (ALS). The muscles show a denervation type of hemoglobin A1c level suggests a diagnosis of diabetes mellitus,
grouped atrophy from loss of lower motor neurons in ante- and diabetic patients are most prone to peripheral neuropa-
rior horns of the spinal cord. The “bulbar” form of ALS thies and autonomic neuropathies. Hyponatremia from diabe-
affects mainly cranial nerve nuclei and has a more aggressive tes insipidus may result in obtundation.
course. Cortical upper motor neurons may also be lost, but
mental function is preserved in ALS. Ependymal cells line PBD9 1305 BP9 835 PBD8 1281–1282 BP8 890–891
ventricles, which are normal in ALS. Microglial cells have a
macrophage-like function and may be involved in demyelin- 6 6 B He may initially have had an infiltrating astrocytoma,
ating plaques of multiple sclerosis that can produce various which is the most common primary brain neoplasm in adults,
motor signs and symptoms over time, but symmetry is not typically arising in a cerebral hemisphere. Lower grade astrocy-
a feature of this disease. Oligodendrocytes provide myelin tomas in adults may have a more indolent course. Some of these
to axons in the CNS. Parkinson disease with loss of substan- patients go on to develop a high-grade glioma known as second-
tia nigra pigmented neurons is characterized by rigidity and ary glioblastoma. Most glioblastomas arise de novo (primary
involuntary movements, not by muscular weakness. Hun- glioblastoma) and have MDM2 mutations. Regardless of origin,
tington disease with loss of spiny neurons in the caudate glioblastomas are aggressive and have a poor prognosis. Diffuse
nucleus causes abnormal movements, not weakness, and large B-cell lymphoma is the most common type of “primary”
there can be associated dementia over time. CNS lymphoma (without evidence for disease elsewhere); some
arise in immunocompromised patients. Hemangioblastomas
PBD9 1300–1301 BP9 841 PBD8 1324–1325 BP8 896 are uncommon neoplasms arising in the cerebellum, often with
von Hippel–Lindau disease, and associated with polycythemia.
6 3 B In children, an inherited form of CNS disease that Medulloblastomas and pilocytic astrocytomas are usually child-
accounts for a progressively worsening course should be hood brain tumors arising in the posterior fossa.
suspected. The leukodystrophies are various inborn errors
PBD9 1306–1308 BP9 842–843 PBD8 1330–1332 BP8 882
4 5 4 U N I T I I Diseases of Organ Systems
67 A Primary malignant neoplasms of the brain in chil- often arise at the cerebellopontine angle in the eighth cra-
dren most often occur in the posterior fossa. The two most nial nerve.
common neoplasms at this site are pilocytic (cystic cerebel-
lar) astrocytoma and medulloblastoma. Pilocytic astrocy- PBD9 1310–1311 BP9 844 PBD8 1336–1337 BP8 884–885
toma is slow growing and has a better overall prognosis than
glial neoplasms in adults. Both may enlarge and block CSF 71 B The MRI shows a 4-cm mass in the cerebellar ver-
flow, causing hydrocephalus. Ependymomas can occur in mis, along with dilation of the third and lateral cerebral ven-
childhood, but are most likely to arise in the fourth ventricle. tricles, consistent with medulloblastoma. Most intracranial
A hemangioblastoma is a rare cystic mass in adults, typi- neoplasms in children are located in the posterior fossa. The
cally arising in the cerebellum, and may be associated with medulloblastoma, one of the “blue cell tumors” of child-
polycythemia. Medulloblastomas often occur in the cerebel- hood, arises in the midline, and the cells can seed into the
lar midline, are composed of primitive round blue cells, and CSF. A glioblastoma is also a high-grade malignancy that
have a poor prognosis. Meningiomas occur in adults; they could seed the CSF, but this neoplasm occurs in adults in a
are circumscribed, solid mass lesions adjacent to the dura, cerebral hemisphere. Schwannomas most often involve the
and may be multiple in neurofibromatosis. A schwannoma eighth cranial nerve, are benign neoplasms, and do not seed
typically arises in cranial nerve VIII in adults. the CSF. Ependymomas can occur in children, but they typi-
cally arise in the ventricles. Metastatic lesions may involve
PBD9 1309 BP9 843 PBD8 1332–1333 BP8 882–883 the gray-white junction, but are uncommon in children.
6 8 E Oligodendrogliomas tend to have a better progno- PBD9 1312–1313 BP9 844–845 PBD8 1336–1337 BP8 884–885
sis than most other glial neoplasms. Pilocytic astrocytomas
with BRAF mutations tend to be less circumscribed. Diffuse 7 2 D Non-Hodgkin lymphomas, including large B-cell
large B-cell lymphomas can occur in association with AIDS; lymphomas, are uncommon in the brain, but they may be
they are negative for glial fibrillary acidic protein (GFAP), seen in immunocompromised patients, particularly patients
but positive for CD19 and CD20. Medulloblastomas are pos- with AIDS. They tend to be multifocal. Cytomegalovirus
terior fossa tumors that occur in children, and those with infection is common in AIDS, but it is unlikely to produce
poor prognosis often have c-MYC amplification. Classic glio- mass lesions. A glioblastoma can be a large infiltrative and
blastomas are highly aggressive, infiltrative gliomas, often destructive mass, but the cells are typically glial fibrillary
with EGFR alterations. acidic protein (GFAP) positive and CD19 negative. Kaposi
sarcoma can occur in association with HIV infection, but CNS
PBD9 1309–1310 BP9 843–844 PBD8 1333–1334 BP8 883–884 involvement is rare, and the cells are CD34 positive. Progres-
sive multifocal leukoencephalopathy produces granular
69 B The myxopapillary variant of ependymoma is more white matter lesions with large, bizarre oligodendrocytes
common in adults than in children. Ependymomas that infected with JC polyomavirus. Toxoplasmosis can produce
arise in the ventricles (usually the fourth ventricle) are more multiple mass lesions, but they are chronic abscesses that are
common in the first 2 decades of life. Choroid plexus papil- filled with necrotic material and surrounded by gliosis; Toxo-
lomas are rare tumors that arise in the cerebral ventricles. plasma pseudocysts may be found in the abscesses.
Meningiomas most often arise in the cranial cavity and
have plump, pink, round to spindle-shaped cells, often with PBD9 1313–1314 BP9 845 PBD8 1337 BP8 885
psammoma bodies. Metastases to the spinal cord are uncom-
mon. Neurofibromas are more likely to arise in peripheral 7 3 C This tan-yellow mass is a meningioma that typically
nerves, although in neurofibromatosis type 1, they can arise is a circumscribed lesion that arises from meningothelial cells
in many sites. A pilocytic astrocytoma is a common pediat- of the arachnoid and appears as though it is grossly attached
ric primary intracranial neoplasm; it arises in the posterior to the overlying dura. They are most often seen in women. A
fossa. A schwannoma most often occurs in cranial nerve VIII, parasagittal, sphenoid ridge, or subfrontal location, is typi-
although neurofibromatosis may be associated with multiple cal. Most meningiomas are biologically benign, but they can
schwannomas. invade and some are more aggressive. Gliomas, including
astrocytomas, are most often found within a cerebral hemi-
PBD9 1310–1311 BP9 844 PBD8 1334–1335 BP8 884 sphere in an adult. Ependymomas are seen within ventri-
cles or on the distal spinal cord. The parasagittal location is
70 B In children, ependymomas most often arise in the unusual for a metastatic lesion, although some malignancies,
floor of the fourth ventricle and can obstruct the flow of such as breast carcinomas, may involve the meninges in a dif-
CSF (obstructive, noncommunicating hydrocephalus). fuse fashion (so-called carcinomatous meningitis). Tubercu-
Most childhood brain neoplasms are found in the posterior lomas are granulomas large enough to produce a mass effect
fossa, including pilocytic astrocytomas that arise in a cere- and are rare complications of disseminated tuberculosis and
bellar hemisphere and appear as a cystic mass with a mural often appear at the base of the brain.
nodule and tumor cells with hairlike processes. Medullo-
blastomas are also childhood tumors, and they arise in the PBD9 1314–1315 BP9 846 PBD8 1338–1339 BP8 885–886
midline cerebellum and are composed of undifferentiated,
primitive blue cells. Glioblastomas are adult neoplasms 7 4 D Multiple discrete neoplasms in the CNS found at the
arising in the cerebral hemispheres. Schwannomas most gray-white junction are more likely to be metastases than a
C H A P T E R 2 8 Central Nervous System 4 5 5
primary brain tumor. Tumor cells may reach the brain in the mutations and cortical hamartomas, and von Hippel–Lindau
form of emboli through the cerebral arterial circulation. Most syndrome with VHL mutations and hemangioblastomas.
embolic events occur at the gray-white junction, where nar-
rowing and acute branching of the vessels tend to trap emboli. PBD9 1247, 1317–1318 BP9 806–807 PBD8 1340–1341
The distribution of the middle cerebral artery, which receives BP8 899–900
the most blood, is the most likely location. Metastases from
malignant melanomas are often widely disseminated, with 7 7 E Tuberous sclerosis is one of the phakomatoses, a
multiple mass lesions in organ sites of involvement. Glioblas- group of rare inherited disorders in which hamartomas and
tomas are large, malignant primary glial neoplasms; they are neoplasms develop throughout the body, along with cuta-
invasive, but do not typically appear as multiple small lesions. neous abnormalities. Patients with tuberous sclerosis have
A hemangioblastoma is a rare cystic mass in adults, typically cortical tubers, which are hamartomas of neuronal and glial
arising in the cerebellum, and may be associated with poly- tissue; other characteristic findings include renal angio-
cythemia. Meningiomas are circumscribed, solid mass lesions myolipomas, renal cysts, subungual fibromas, and cardiac
adjacent to the dura; they may be multiple in patients with rhabdomyomas. In Down syndrome (trisomy 21), patients
neurofibromatosis. Cerebral malignant lymphomas are rare may develop acute leukemia, but not brain neoplasms, and
except in HIV-positive patients. Oligodendrogliomas are sol- individuals who survive to middle age develop Alzheimer
itary, circumscribed mass lesions that occur in the cerebral disease. Krabbe disease is a leukodystrophy that results in
hemispheres of adults. deficiency of galactocerebroside β-galactosidase and an onset
of neurologic deterioration in infancy. Neurofibromatosis
PBD9 1315–1316 BP9 846–847 PBD8 1339 BP8 886–887 type 1 is characterized by deforming cutaneous and visceral
neurofibromas, cutaneous café-au-lait spots, and neurofibro-
75 E The multiple pigmented skin lesions and optic nerve sarcomas. In neurofibromatosis type 2, acoustic schwanno-
glioma strongly suggest the diagnosis of neurofibromatosis mas, meningiomas, gliomas, and ependymomas are present.
type 1. Patients with this condition, which has an autosomal Von Hippel–Lindau disease is characterized by hemangio-
dominant inheritance, have multiple large café-au-lait spots blastomas in the cerebellum, retina, and spinal cord, and by
on the skin, and there is a propensity for development of pheochromocytomas.
multiple nerve sheath tumors (schwannomas or neurofibro-
mas). CNS gliomas also may occur. The nerve sheath tumors PBD9 1316–1317 BP9 847 PBD8 1342–1343 BP8 901
may become malignant and metastasize, most commonly to
the lungs. Of the other neoplasms listed, only meningioma 7 8 C Hemangioblastomas are part of the spectrum of
is associated with neurofibromatosis type 1, but it occurs neoplasms seen in association with von Hippel–Lindau dis-
intracranially. ease. The VHL gene encodes for a ubiquitin-ligase compo-
nent important in the degradation pathway of HIF, and this
PBD9 1247, 1317–1318 BP9 808 PBD8 1342 BP8 900–901 increases vascular endothelial growth factor (VEGF) expres-
sion to drive vascular proliferation. Cushing syndrome
7 6 A A schwannoma in this location also is known as a cer- with increased corticosteroid production can be related to
ebellopontine angle tumor. Schwannomas in this location arise ectopic ACTH production by a carcinoma. Cushing dis-
from cranial nerve VIII; they are also called acoustic neuro- ease is caused by an ACTH-producing adenohypophyseal
mas. Most schwannomas act as benign, slow-growing tumors adenoma. Hypercalcemia of malignancy often results from
that can be completely resected. Having bilateral acoustic parathormone-related peptide production by a carcinoma.
schwannomas is virtually pathognomonic for neurofibro- Syndrome of inappropriate antidiuretic hormone (SIADH)
matosis type 2. Other familial tumor syndromes involving may be caused by neuroendocrine tumors such as small cell
brain include Li Fraumeni syndrome with p53 mutations lung carcinomas. Carcinomas, particularly adenocarcinomas,
and medulloblastomas, Gorlin syndrome with PTCH muta- may produce hypercoagulability (Trousseau syndrome).
tions and medulloblastomas, tuberous sclerosis with TSC1
PBD9 1317 BP9 847 PBD8 1343 BP8 901
29C H A P T E R
The Eye
PBD9 Chapter 29 and PBD8 Chapter 29: The Eye
1 A 39-year-old man has increasing pain with left eye 4 A 27-year-old woman has had pain with cloudiness of
movement and swelling for the past week. On examination vision in the right eye for the past 2 days. A similar episode
he has proptosis and ophthalmoplegia. There is edema and occurred a year ago. On physical examination, there is no con-
erythema of the eyelid with marked tenderness on palpation. junctival erythema or vascular injection. Funduscopic exami-
A purulent nasal discharge is present. Which of the following nation shows no retinal lesions. A slit lamp examination with
orbital conditions is he most likely to have? fluorescein dye shows a dendritic ulcer on the right cornea.
A Cellulitis Which of the following infectious agents has most likely pro-
B Graves disease duced these findings?
C Hemangioma A Chlamydia trachomatis
D Non-Hodgkin lymphoma B Cytomegalovirus
E Sarcoidosis C Herpes simplex virus
2 A 7-year-old child has had worsening performance in D Neisseria gonorrhoeae
school for the past 4 months from decreased vision. Examina- E Staphylococcus aureus
tion of the right eye shows diffuse punctate inflammation of
the cornea and pannus extending as a growth of fibrovascular 5 A 26-year-old man has had severe visual impairment
tissue from conjunctiva onto the cornea. Microscopic examina- since birth. He is legally blind without his glasses, but his astig-
tion of a corneal scraping shows lymphocytes, plasma cells, matism in both eyes is so severe that he cannot get a correc-
neutrophils, and scattered corneal epithelial cells that have cy- tion better than 20/100 with eyeglasses. He tries rigid contact
toplasmic inclusion bodies. Which of the following infectious lenses and gets a correction of 20/40. Which of the following
agents is most likely to produce these findings? ocular conditions is he most likely to have?
A Chlamydia trachomatis A Keratoconus
B Cytomegalovirus B Pterygium
C Herpes simplex virus C Stromal dystrophy
D Rubella virus D Trachoma
E Treponema pallidum E Vitamin A deficiency
3 An 82-year-old man still surfs every week at Waikiki
beach. He has noted clouding of vision on the right for the 6 A 34-year-old man has had decreasing vision for the
past year. On physical examination of the right eye there is a past 3 years and now has severely impaired vision in both
whitish irregular lesion on the conjunctiva extending onto the eyes. His brother is similarly affected. Both parents have nor-
cornea. Which of the following is the most likely risk factor for mal vision. Ocular examination shows diffuse cloudiness of
his ocular lesion? the anterior stroma with aggregates of gray-white opacities in
A Chlamydia trachomatis infection the axial region of the corneal stroma. He undergoes bilateral
B Hyperglycemia corneal transplantation. The diseased corneas show basophilic
C Hypertension deposits in the stroma that stain positively for keratan sulfate.
D Sunlight exposure What is the most likely diagnosis?
E Vitamin A deficiency A Cataract formation
B Keratomalacia
456 C Macular dystrophy
D Pterygium
E Trachoma
7 A 29-year-old woman has developed malaise with nau- C H A P T E R 2 9 The Eye 4 5 7
sea over the past month. On physical examination, she has an
erythematous rash on the cheeks of her face. Laboratory stud- 10 A 48-year-old man was not using protective goggles
ies show a serum creatinine level of 3.3 mg/dL, urea nitrogen while ripping plywood on his table saw, and he sustained a
of 33 mg/dL, positive ANA of 1:2048, and positive anti–double- penetrating injury to the left eye. A wood splinter is removed.
stranded DNA of 1:512. A renal biopsy specimen shows a On funduscopic examination, there is a partial uveal prolapse,
proliferative glomerulonephritis. She receives long-term high- but he still has vision in the left eye. Three weeks later, he has
dose glucocorticoid therapy. What ocular complication is this loss of accommodation, photophobia, and blurred vision in
patient most likely to develop? the right eye. Choroidal infiltrates are now seen on fundu-
A Background retinopathy scopic examination. What is the most likely diagnosis?
B Cataracts A Aspergillus fumigatus infection
C Corneal stromal dystrophy B Fuchs dystrophy
D Granulomatous uveitis C Sarcoidosis
E Macular degeneration D Sympathetic ophthalmia
E Undiagnosed trauma
8 An 82-year-old woman has had increasing visual prob- 11 A 61-year-old woman has had decreasing visual acuity
lems that are worse in the right eye over the past 2 years. She in the right eye for 6 months. She then experienced sudden
is unable to see clearly when looking straight ahead because of loss of part of the vision in the left eye, which occurred “as
cloudiness and opacification and has great difficulty reading though a shade had been pulled across” her field of view. On
printed material. Her peripheral vision is better. Her left eye is funduscopic examination, there is a dark uveal mass. The enu-
similarly affected and is shown in the figure. What pathologic cleated eye is shown in transverse section in the figure. What
process has most likely occurred in this woman? is the most likely diagnosis?
A Keratomalacia of the cornea A Granulomatous uveitis
B Nuclear sclerosis of the lens B Malignant hypertension
C Open-angle glaucoma C Melanoma
D Retinal macular degeneration D Ocular trauma with hematoma
E Sympathetic ophthalmia E Retinoblastoma
F Toxoplasmosis
9 A 77-year-old woman has experienced increasing pain
accompanied by clouded vision in the right eye for the past 36
hours. She has worn corrective lenses for hyperopia for the past
70 years. On physical examination, there are no lesions of the
cornea or crystalline lens. On funduscopic examination, there is
excavation of the optic cup on the right. Which of the following
pathologic processes is most likely to produce these findings?
A Amyloid deposition within posterior chamber
vitreous
B Crystalline lens dislocation into the anterior
chamber
C Increased aqueous humor production by the ciliary
body
D Resistance of aqueous humor outflow into Schlemm
canal
E Shallow anterior chamber obstructing aqueous
humor outflow
F Thromboembolism to the central retinal artery
4 5 8 U N I T I I Diseases of Organ Systems 15 A 23-year-old primigravida with preeclampsia gives
12 A 68-year-old woman with a history of left ventricular birth prematurely at 32 weeks’ gestation. The infant’s Apgar
congestive heart failure has had decreased visual acuity for scores are 4 and 6 at 1 minute and 5 minutes, respectively. The
the past 5 years. She has no ocular pain. Her intraocular pres- infant has hyaline membrane disease and is intubated and ad-
sure is normal. Findings on funduscopic examination include ministered positive pressure ventilation with 100% inspired
arteriolar narrowing, flame-shaped hemorrhages, cotton-wool oxygen. The infant survives and is discharged on the twenty-
spots, and hard, waxy exudates. Which of the following un- third day of life. Two months later, the mother notices that
derlying diseases is she most likely to have? the infant does not always respond visually to her presence.
A Advanced atherosclerosis The infant is examined and is found to be blind in nasal visual
B Cerebral edema fields. What is the most likely diagnosis?
C Diabetes mellitus A Cataracts
D Hypertension B Keratomalacia
E Retinitis pigmentosa C Macular degeneration
D Retinitis pigmentosa
E Retrolental fibroplasia
13 A 68-year-old woman has had chronic renal failure for
10 years and has been on hemodialysis. She had a myocardial 16 A 15-year-old boy from Eastern Arabia has experienced
infarction last year. She now has worsening vision bilaterally. episodes of chest, abdominal, and back pain as well as fatigue
The figure shows findings representative for her retina. Which for the past 10 years. Physical examination is not remarkable.
of the following laboratory test findings in her blood is she Laboratory investigations show hemoglobin, 8 g/dL; hema-
most likely to have? tocrit, 24.7%; MCV, 95 μm3; and total serum bilirubin, 2.1
A Antinuclear antibody titer of 1:1024 mg/dL. The serum AST, ALT, albumin, and total protein are
B Ferritin of 555 ng/mL normal. Prothrombin time and partial thromboplastin time
C Hgb A1c of 9.6% are normal. Examination of a peripheral blood smear shows
D Renin activity of 9 ng/mL/hr reticulocytosis and polychromasia with occasional deformed
E Total cholesterol 265 mg/dL RBCs shaped like crescents. This patient is at increased risk for
14 A 74-year-old man suddenly lost the upper half of the developing which of the following ocular complications?
visual field in the right eye. Before this event, he had decreas- A Cataract
ing visual acuity in both eyes for the past 6 years. On physical B Intraretinal hemorrhage
examination, his height is 170 cm (5 feet 8 inches), and weight C Keratoconus
is 92.5 kg (body mass index 32). Laboratory studies show a D Secondary angle-closure glaucoma
fasting serum glucose level of 165 mg/dL. What underlying E Uveitis
pathologic process is most likely to account for the sudden loss
of vision in his right eye? 17 A 75-year-old woman with diabetes mellitus and con-
A Dendritic corneal ulcer gestive heart failure has sudden loss of vision in her left eye.
B Macular degeneration Funduscopic examination shows a cherry-red appearance of
C Retinitis pigmentosa the foveola, whereas the remaining retina appears pale. No ab-
D Traction retinal detachment normalities of the right eye are noted. Which of the following
E Uveal malignant melanoma is the most likely cause for her sudden unilateral visual loss?
A Central retinal artery occlusion
B Cytomegalovirus retinitis
C Primary angle-closure glaucoma
D Proliferative retinopathy
E Tay-Sachs disease
18 A study is conducted of children 1 to 2 years of age who
appeared healthy when born at term, but developed blind-
ness and failure to meet developmental milestones for neural
development. On funduscopic examination they have pale
retinae with prominent red macular regions. A deficiency of
which of the following enzymes is most likely to be found in
these children?
A α-l-Iduronidase
B Galactosylceramidase
C Glucocerebrosidase
D Hexosaminidase A
E Lysosomal glucosidase
19 A pharmaceutical company is developing a product C H A P T E R 2 9 The Eye 4 5 9
that would be useful to prevent age-related visual loss. A co-
hort of individuals 60 to 80 years old is followed for 5 years 23 A 3-year-old boy has been observed by his parents to be
with periodic examinations of visual acuity, funduscopy, and increasingly clumsy for the past 6 months. On physical exami-
fluorescein angiography. Some of these individuals develop nation there is leukocoria with absence of the red reflex in the
progressive loss of vision characterized initially by diffuse de- left eye. The eye is enucleated; the microscopic appearance of
posits in Bruch membrane and by atrophy of retinal pigment an intraocular mass is shown in the figure. What is the most
epithelium. Later, a subset of these patients has a further de- likely diagnosis?
cline in vision because of development of choroidal neovascu- A Glioma
larization. An antagonist to which of the following molecules B Melanoma
is most likely to be useful in reducing vision loss in this subset C Medulloblastoma
of patients? D Retinoblastoma
A Epidermal growth factor (EGF) E Squamous cell carcinoma
B Insulin-like growth factor (IGF) 24 A 70-year-old man with atrial fibrillation and poorly
C Platelet-derived growth factor (PDGF) controlled hypertension is recovering from right hip replace-
D Transforming growth factor beta (TGF-β) ment surgery. He has had a worsening headache for the past
E Vascular endothelial growth factor (VEGF) day. He is receiving anticoagulant therapy. On physical ex-
amination, he is afebrile with blood pressure 170/110 mm Hg.
20 A 78-year-old man with a 30 pack-year history of smok- On funduscopic examination, there is papilledema of the left
ing has had decreasing vision, mainly in a central pattern, for eye. What is the most likely cause of the papilledema?
the past 3 years. He has no ocular pain. Intraocular pressures A Alzheimer disease
are normal. There are no abnormalities of the cornea or crys- B Glaucoma
talline lens. On funduscopic examination, the retinal pigment C Macular degeneration
epithelium appears atrophic, and deposits are seen in the D Optic neuritis
Bruch membrane. What is the most likely diagnosis? E Intracranial hemorrhage
A Macular degeneration F Schwannoma
B Proliferative retinopathy 25 A 72-year-old woman has had decreasing vision for the
C Retinal detachment past year. She now has increasing headaches. She has worn
D Retinitis pigmentosa glasses since childhood because of myopia. Funduscopic ex-
E Retrolental fibroplasia amination shows deepening of the optic cup with excavation.
The surrounding retina appears normal. Screening of which of
21 A 33-year-old man has had increasing difficulty seeing the following would most likely have detected the disease that
at night, but has no problems with his vision during the day. led to these findings?
Three years later, his daytime visual acuity also is decreasing. A Blood pressure
Funduscopic examination now shows a branching reticulated B Homocystinuria
pattern to the retina. The optic disc appears pale and waxy, C Intraocular pressure
and there is attenuation of retinal blood vessels. These find- D Serum glucose
ings are most characteristic of what condition? E Visual acuity
A Arteriosclerotic retinopathy
B Hypertensive retinopathy
C Macular degeneration
D Proliferative retinopathy
E Retinitis pigmentosa
22 A 22-year-old woman gives birth at term to a boy after
an uncomplicated pregnancy. No abnormalities are noted on a
newborn physical examination. During infancy, a well-infant
checkup shows leukocoria in the right eye. The eye is enucle-
ated. Molecular analysis of the enucleated tumor indicates loss
of cell cycle control in the tumor cells. In comparison, the in-
fant’s skin fibroblasts do not show any molecular a bnormality.
Which of the following statements regarding this infant is
most accurate?
A Inheritance of a parental mutated RB gene locus
B Loss of both RB gene copies in the eye tumor
C Risk for a contralateral eye tumor in childhood
D Risk for future development of osteosarcoma
E Siblings at risk for a similar tumor
4 6 0 U N I T I I Diseases of Organ Systems
ANSWERS eye drops at birth are employed to prevent ophthalmia neo-
natorum. Staphylococcus aureus is a common infection at
1 A Orbital cellulitis can be due to spread of infection many tissue sites, and can produce conjunctivitis, which was
from adjacent paranasal sinuses, such as ethmoid air cells. not evident in this case.
Organisms may include Staphylococcus aureus, Streptococcus
pyogenes, Streptococcus pneumoniae, and Haemophilus influ- PBD9 1325 PBD8 1351
enzae. In diabetic ketoacidosis, mucormycosis should be
considered. Idiopathic orbital inflammation (inflammatory 5 A Keratoconus patients are typically not candidates for
pseudotumor) may present similarly, but is noninfectious. laser in situ keratomileusis (LASIK) because the marked cor-
Graves disease is likely to present with bilateral proptosis, neal thinning with breaks in the Bowman layer gives their
but without inflammatory changes, because accumulation corneas a conical shape. Penetrating keratoplasty may be
of extracellular matrix proteins is the etiology. Hemangioma performed. Corneal transplantation can also be considered
in children and lymphoma in adults are mass lesions of the as treatment for keratoconus. A pterygium is a localized area
orbit, likely without inflammatory changes. Sarcoidosis pro- of conjunctival opacification from degenerative changes;
duces granulomatous inflammation without acute changes. unlike a pinguecula, it extends onto the cornea and may
interfere with vision. Stromal dystrophies are uncommon
PBD9 1320–1321 PBD8 1347 inherited conditions with corneal clouding from deposition
of mucopolysaccharides. Trachoma occurs from infection
2 A Trachoma is a major cause of blindness worldwide. with Chlamydia trachomatis and may lead to corneal scarring
The initial inflammation from infection is followed by pro- with blindness. Vitamin A deficiency can lead to keratoma-
gressive conjunctival scarring with eyelid involvement, so lacia and eventual blindness if the deficiency is not treated.
that the eyelashes turn inward (trichiasis) to produce scarring
of the conjunctiva and cornea. In children, cytomegalovirus PBD9 1326 PBD8 1352
(CMV), one of the herpesviruses, is a rare cause of ocular
infection. CMV produces prominent intranuclear inclusions. 6 C Inherited corneal stromal dystrophy has several
Herpetic keratitis can result in ulceration and scarring; her- forms, and most are autosomal dominant. However, the
pesviruses have intranuclear inclusions. Congenital rubella, most severe form is macular dystrophy, which has an auto-
which is now a rare disease because of immunization, pro- somal recessive form of inheritance. It is essentially a form
duces a retinopathy. Congenital infections with Treponema of mucopolysaccharidosis confined to the cornea in which
pallidum result in an interstitial keratitis. keratan sulfate is deposited. Cataracts are seen most often in
elderly individuals and result from opacifications of the crys-
PBD9 1323 BP9 311 PBD8 1349 BP8 323 talline lens. Keratomalacia can be a consequence of vitamin
A deficiency. A pterygium is a localized area of basophilic
3 D A pterygium can extend onto the cornea but does not degeneration of conjunctival epithelium that extends onto
cross the pupillary axis; it may induce mild astigmatism to the cornea. Trachoma is caused by infection with Chlamydia
affect vision. A pinguecula does not impinge upon the cor- trachomatis.
nea, but it does affect distribution of the tear film to produce
focal dehydration and corneal depression. Both of these PBD9 1326–1327 PBD8 1352–1353
lesions are composed of fibrovascular connective tissue, and
ultraviolet light is the driving force. Trachoma leads to con- 7 B Cataracts of the crystalline lens are an important
junctival scarring that is not so focal. Diabetes mellitus with complication of systemic therapy with glucocorticoids.
hyperglycemia is more likely to affect the crystalline lens or This patient has systemic lupus erythematosus with lupus
the retina. Hypertensive retinopathy may occur. Vitamin A nephritis. Cataracts can be caused by aging, diabetes melli-
deficiency can lead to keratomalacia and not a localized scar. tus, glaucoma, ultraviolet light, or irradiation. Retinopathy
is most often a feature of diabetes mellitus or hypertension.
PBD9 1323 PBD8 1349 Stromal dystrophies are inherited conditions that affect the
cornea. Granulomatous uveitis occurs with sarcoidosis. Mac-
4 C The most common cause of corneal dendritic ulcers ular degeneration is most often a disease of central vision in
is herpes simplex virus infection. Such ulcers can perforate the elderly.
through to the globe, which is a medical emergency. Some
chronic herpetic corneal infections cause localized opacity. PBD9 1327 PBD8 1353
Lymphocytes and plasma cells, and viral inclusions in the
corneal epithelial cells, are present. Trachoma, an infection 8 B Nuclear sclerosis of the lens leads to cataracts in
with Chlamydia trachomatis, is seen most often in children and elderly individuals, typified by the lens opacification shown
produces inflammation leading to extensive corneal and con- in the figure. This change causes opacification owing to
junctival scarring. Cytomegalovirus infection rarely causes compression of the lens fibers in the central (nuclear) por-
corneal lesions. It can cause retinitis in congenital infections tion of the lens. Keratomalacia can produce corneal scarring
and in immunocompromised adults. Neisseria gonorrhoeae with opacification, but not in a central distribution pattern.
infection can occur in sexually active persons, and it can be
transmitted to neonates at birth, so prophylactic silver nitrate
C H A P T E R 2 9 The Eye 4 6 1
Glaucoma results from increased intraocular pressure and Ocular trauma may lead to retinal detachment, but without
damages the optic nerve, and it is not characterized by loss a mass; trauma may also induce an autoimmune response
of central vision, but more likely peripheral vision. Macular known as sympathetic ophthalmia with inflammation in the
degeneration also occurs in elderly individuals and results in opposite eye, but has no mass effect. Retinoblastoma most
loss of central vision, but it does not cause cloudiness. Sym- often occurs in children, and the tumor is not pigmented.
pathetic ophthalmia in one eye occurs after trauma to the Toxoplasmosis can produce small foci of inflammation, but
other eye. not a mass.
PBD9 1327 PBD8 1353 PBD9 1331–1332 PBD8 1358
9 E In some older individuals with hyperopia, the iris is 12 D Hypertensive retinopathy results from long-standing
displaced forward to narrow the angle at the anterior cham- hypertension, with progressive changes that begin with gener-
ber, obstructing flow of aqueous humor, so-called primary alized narrowing of the arterioles and proceed to the changes
angle-closure glaucoma, which manifests with acute pain. seen in this case. The pressure load from systemic hyperten-
Increased pressure on the optic nerve causes excavation and sion causes hypertrophy and failure of the left side of the
produces progressive visual loss. Mutations in the myocilin heart. Arteriosclerotic retinopathy causes vascular changes,
(MYOC) and the optineurin (OPTN) genes may account for including arteriovenous nicking and hyaline arteriolosclero-
some cases of primary open-angle glaucoma. Amyloid depo- sis with “copper wire” and “silver wire” arterioles. Cerebral
sition is quite rare and does not increase intraocular pressure. edema may result in papilledema. Various findings are asso-
Crystalline lens dislocation can occur with trauma and with ciated with diabetic retinopathy, including capillary micro-
Marfan syndrome. Increased production of aqueous humor aneurysms, cotton-wool spots, arteriolar hyalinization, and
is a rare cause of glaucoma. Increased resistance to outflow more severe changes of proliferative retinopathy with neo-
of aqueous into Schlemm canal is typical of primary open- vascularization. Retinitis pigmentosa describes a variety of
angle glaucoma, which occurs in individuals with myopia. abnormalities that arise as an inherited condition that may
Thrombosis or embolism to the central retinal artery can lead begin later in life (but usually earlier) and produce a waxy
to occlusion with edema, pallor, and a cherry-red spot in the pallor of the optic disc.
fovea; unless the ischemia is of short duration, blindness
results. PBD9 1333–1334 PBD8 1359
PBD9 1327–1329 PBD8 1353–1355 1 3 C Proliferative retinopathy with neovascularization
from long-standing diabetes mellitus is shown in the figure.
10 D Sympathetic ophthalmia is an unusual, but devastat- Several other ocular changes also can occur with diabetes
ing, form of uveitis that can complicate penetrating ocular mellitus, including hemorrhages, arteriolar hyalinization,
trauma. It results from the release of a sequestered antigen cotton-wool spots, and fibroplasia. This patient’s renal failure
from one eye that causes an immune response with inflam- and cardiovascular disease are typical of diabetes mellitus.
matory reaction in the opposite eye. To prevent this compli- This funduscopic finding is not seen with autoimmune dis-
cation, the traumatized eye must be removed before inflam- eases, hemochromatosis, hypertension, or hyperlipidemia.
mation begins in the opposite eye. Trauma alone cannot
produce this spectrum of findings. Louis Braille, the inven- PBD9 1334–1336 BP9 747 PBD8 1359–1360 BP8 784
tor of the Braille alphabet for tactile reading of text, had an
eye injury that led to sympathetic ophthalmia. Infection with 1 4 D The clinical features described suggest retinal detach-
Aspergillus is unlikely to become disseminated in an immu- ment, which occurs in a late stage of proliferative retinopa-
nocompetent individual, and is not typically associated with thy associated with diabetes mellitus. The neovascularization
traumatic eye lesions. Sarcoidosis can affect the eye, but results in a membrane with fibrosis that increases traction
lesions in the choroid are uncommon. Fuchs dystrophy is an on the retina, leading to sudden detachment. Dendritic cor-
inherited condition that affects the corneal endothelium. neal ulceration suggests infection with herpes simplex virus.
Macular degeneration is a common cause of decreased vision
PBD9 1330 PBD8 1356 in elderly individuals, but not of retinal detachment. Retinitis
pigmentosa is an inherited, degenerative condition that is not
1 1 C The pigmented uveal mass is a melanoma causing related to diabetes mellitus. Uveal melanomas may cause reti-
retinal detachment, because the mass lifted off the overlying nal detachment, but they are not a feature of diabetes mellitus.
retina. After skin, the eye is the most common site for pri-
mary malignant melanoma. This is the most common intra- PBD9 1334–1336 BP9 747 PBD8 1360 BP8 571
ocular malignancy in adults. Uveal melanomas can involve
the choroid, the iris, or the ciliary body. They are often pig- 1 5 E Retrolental fibroplasia is a complication of prema-
mented. In addition to causing retinal detachment, as in ture birth that results from oxygen toxicity to the immature
this case, they may cause choroidal hemorrhage or macular retinal vasculature, leading to neovascularization of the ret-
edema. Granulomatous uveitis can occur from sarcoidosis, ina with growth into the vitreous. The incompletely vascu-
but the inflammation does not produce a large mass lesion. larized lateral aspects of the retina are most severely affected
Hypertensive retinopathy can produce small hemorrhages. by ischemia and subsequent up-regulation of vascular
4 6 2 U N I T I I Diseases of Organ Systems
endothelial growth factor (VEGF). In some cases, scarring of α-l-iduronidase affects mainly connective tissues. Galac-
continues and causes retinal detachment. Cataracts also are tosylceramidase deficiency leads to Krabbe disease, a leuko-
seen in older individuals. Keratomalacia is a feature of vita- dystrophy affecting cerebral white matter. Gaucher disease
min A deficiency that develops over a longer period. Macu- from glucocerebrosidase deficiency is most often nonneu-
lar degeneration is a disease of elderly individuals. Retinitis ropathic. Lysosomal glucosidase deficiency leads to Pompe
pigmentosa can be inherited in various patterns and has a disease.
variable onset from childhood through older age.
PBD9 151–152, 1338 BP9 229–230 PBD8 150–152, 1364
PBD9 1336 PBD8 1361 BP8 235–237
16 B In sickle cell anemia the sickled RBCs can occlude the 19 E Age-related macular degeneration (AMD) is the lead-
retinal microvasculature as oxygen tension decreases and the ing cause of visual loss in the Western world. Its advanced
RBCs assume a sickle shape. These vascular occlusions can stages (exudative AMD, or the “wet” form with choroidal
cause preretinal, intraretinal, and subretinal hemorrhages. neovascularization) are characterized by extensive choroidal
Organization of preretinal hemorrhages can cause retinal neovascularization that is driven by the local production of
traction and detachment. Cataracts are most commonly age- VEGF. Clinical trials indicate that anti-VEGF agents reduce
related, but may be secondary to systemic diseases such as neovascularization and visual loss. None of the other listed
galactosemia, diabetes mellitus, and Wilson disease. Kera- factors significantly affects angiogenesis.
toconus is characterized by progressive thinning of the cor-
nea without any inflammation, which leads to an abnormal PBD9 1338–1339 PBD8 1363–1364
shape that is more conical than spherical, giving rise to severe
astigmatism. This form of corneal degeneration can occur 20 A Macular degeneration is most often an age-related
sporadically or in association with a systemic disease, such condition (AMD) and is the most common cause of decreased
as Marfan syndrome. Secondary angle-closure glaucoma is vision in the elderly. An absence of retinal vessels in the cen-
caused by inflammation of the uvea and consequent forma- ter of the macula may contribute to this disease because the
tion of a neovascular membrane that blocks the trabecular retina has high metabolic demands. The disease may result in
meshwork. Uveitis may occur locally or be part of systemic fibrous metaplasia and scarring of the macular region, caus-
diseases, such as sarcoidosis. ing permanent loss of central vision. A majority of AMD cases
may be related to inherited mutations in the complement factor
PBD9 1336–1337 PBD8 1361–1362 H (CFH) gene, made worse through environmental exposures,
such as cigarette smoke. Proliferative retinopathy is character-
1 7 A Thromboembolization from the diseased heart to ized by neovascularization of the retina. Retinal detachment
the central retinal artery causes a diffuse retinal infarct that may be a complication of diabetic proliferative retinopathy,
obscures the underlying vascular choroid, except where the but not macular degeneration. Retinitis pigmentosa is an
retina is thinner in the fovea, so that it appears red compared inherited disorder that produces a characteristic waxy pallor
to the surrounding pale retina. The other listed choices are of the optic disc. Retrolental fibroplasia is a complication of
typically bilateral processes. Cytomegalovirus retinitis has high-dose oxygen therapy for neonates (often premature).
edematous and hemorrhagic lesions; it is most often seen in
immunocompromised patients. Primary angle-closure glau- PBD9 1338–1339 PBD8 1363–1364
coma typically occurs in hyperopic eyes, and some cases may
be acute, with eye pain from elevated intraocular pressure. 21 E Retinitis pigmentosa describes a range of retinal
Proliferative retinopathy can occur with diabetes mellitus, abnormalities that can be inherited in various patterns, and
but the major change is retinal neovascularization. Tay- progression of the disease is variable. Night blindness caused
Sachs disease seen in infancy and early childhood produces a by loss of rod photoreceptors is an early symptom. Later,
cherry-red spot, because the fovea in the center of the macula the cone photoreceptors also begin to degenerate, produc-
is relatively spared; it contains few ganglion cells that con- ing blindness. Vascular changes are seen with hypertensive
tain the storage product. and arteriosclerotic retinopathies, but these tend to occur in
older adults, with no difference in effects on day or night
PBD9 1337–1338 PBD8 1362 vision. Macular degeneration is seen in elderly individuals
and affects central vision first. Neovascularization is a fea-
1 8 D Tay-Sachs disease is an autosomal recessive inborn ture of diabetic proliferative retinopathy.
error of metabolism due to deficiency of hexosaminidase A,
one of the GM2 gangliosidoses, leading to lysosomal stor- PBD9 1339 PBD8 1364
age of intermediate metabolites in retinal ganglion cells and
neocortical neurons. The cherry-red spot is the least affected 22 B This infant has a sporadic form of retinoblastoma.
area where the thinner foveal area allows the vascularized Both mutations probably arose in the retinoblasts. The infant
choroid to appear more prominent in the pale surrounding did not inherit susceptibility to develop retinoblastoma
affected retina. The remaining choices represent autosomal because both copies of the RB gene are normal in unaffected
recessive conditions that are unlikely to affect the eye. Muco- somatic cells (fibroblasts). If he had inherited one copy of the
polysaccharidosis type I (Hurler syndrome) with deficiency mutant (or deleted) RB gene, all the cells in the body would
C H A P T E R 2 9 The Eye 4 6 3
have only one normal copy of the RB gene. His siblings are Patients receiving anticoagulation, which could be given fol-
at no increased risk of developing retinoblastoma, and he is lowing major surgery, are also at risk for intracranial hemor-
at no increased risk of developing osteosarcoma. For similar rhages. The blood collecting in the subdural space leads to
reasons, risk of developing a retinoblastoma in the left eye increased intracranial pressure. Cerebral amyloid angiopa-
also is no greater than that of the general population. thy can occur in association with Alzheimer disease and can
lead to intracranial hemorrhage, but that is not the risk in
PBD9 1339 BP9 182–184 PBD8 1365 BP8 193, 270–271 this vignette. Glaucoma, with increased intraocular pressure,
produces optic cup excavation (the opposite of papilledema).
2 3 D Retinoblastoma is the most common malignant ocu- Macular degeneration affects the fovea more severely. Optic
lar neoplasm in children. Histologically, there is clustering neuritis leads to decreased visual acuity and is most often
of small blue cuboidal or short columnar cells around a a complication of multiple sclerosis. Schwannomas arise in
central lumen. These clusters are sometimes called Flexner- peripheral nerves, including cranial nerves, but the optic
Wintersteiner rosettes, as shown in the figure. This tumor nerve is really a tract, an extension of the forebrain dienceph-
can spread to the orbit or along the optic nerve. Most cases alon. Thus a glioma could arise in the optic tract, but not a
occurring in children are familial, with an inherited mutated schwannoma.
RB gene. Gliomas may affect the optic nerve in a child, but
the microscopic pattern does not include the rosettes shown. PBD9 1340–1341 PBD8 1366
Melanomas of the eye are seen in adults and have spindle
or polygonal cell patterns, and are often pigmented. Medul- 25 C The increased intraocular pressure with glaucoma is
loblastomas are cerebellar malignancies in children. Retino- believed to cause the loss of nerve fibers, resulting in a charac-
blastomas, medulloblastomas, and neuroblastomas all are teristic cupped excavation of the optic disc. Because there are
forms of small round blue cell tumors seen in children. Ade- no obvious early signs or symptoms, screening for increased
nocarcinomas and squamous cell carcinomas are uncommon pressure is important for detection. Glaucoma has several
neoplasms in children and unlikely to be intraocular. causes; various medications are used to treat the disease.
Hypertension can produce a retinopathy, but not increased
PBD9 1339 BP9 182–184 PBD8 1365 BP8 270–271 intraocular pressure. Homocystinuria is a rare condition that
also increases the risk of atherosclerosis. Hyperglycemia
2 4 E Papilledema results from increased intracranial pres- suggests a diagnosis of diabetes mellitus, which can increase
sure produced by cerebral edema, intracranial hemorrhage, the risk of glaucoma. Visual acuity may be maintained while
or rapidly expanding masses. This patient is most likely to glaucoma is progressing, and loss of acuity alone does not
have a basal ganglia hemorrhage based upon the risk fac- identify the cause.
tor of hypertension. A hemorrhagic stroke from emboliza-
tion is also a possibility, with the history of atrial fibrillation. PBD9 1341 PBD8 1366
30C H A P T E R
Final Review and Assessment
1 A 33-year-old man has experienced onset of chest pain, 3 A 64-year-old man has had a low-volume mucoid diar-
diaphoresis, and dyspnea over the past 6 hours. In the emer- rhea with five bowel movements per day, accompanied by
gency department, he has a serum troponin I level of 6 ng/ cramping abdominal pain, for the past 2 months. The stool
mL. Additional laboratory findings include hematocrit of 41%, is occasionally blood-streaked. On physical examination, he
hemoglobin A1c of 4.2%, total serum cholesterol of 482 mg/dL, appears pale. A colonoscopy is performed; the figure shows
and serum triglyceride of 160 mg/dL. Emergent coronary an- a representative image of the mucosa from the rectum to the
giography shows 65% stenosis of the left circumflex artery and lower portion of the sigmoid. The remaining colonic mucosa
70% stenosis of the left anterior descending artery. He under- appears normal. Biopsy specimens of the affected colon show
goes angioplasty with stent placement. He experiences a series mucosal crypt distortion, focal crypt abscesses, and mixed in-
of transient ischemic attacks 1 year later. He also has pain in flammatory infiltrates extending to the lamina propria. Over
the lower extremities when walking more than 300 m. He is the next 2 years, he develops polyarthritis with no joint defor-
given a drug that inhibits hepatic HMG-CoA reductase. The mity, and uveitis. Which of the following additional diseases
pathogenesis of his underlying disease is most likely related is he most likely to develop?
to a reduction in which of the following cellular receptors? A Atrophic gastritis
A Acetylcholine B Dermatitis herpetiformis
B Glucose C Orchitis
C Hepcidin D Primary sclerosing cholangitis
D Insulin E Rheumatoid arthritis
E LDL F Thyroiditis
2 An 18-year-old woman has had recurrent acute attacks
of dyspnea for the past 10 years. Between these attacks, she has
no medical problems. She is brought to the emergency depart-
ment within an hour of onset of the latest episode. On physical
examination, her temperature is 37.1° C, pulse is 110/min, re-
spiratory rate is 28/min, and blood pressure is 110/70 mm Hg.
Expiratory wheezes are auscultated over the chest bilaterally.
Pulmonary function studies show severe limitation of airflow,
which is relieved on injection of epinephrine. Sputum cytolog-
ic examination shows abundant mucus with an inflammatory
infiltrate dominated by eosinophils, but mixed with neutro-
phils and macrophages. Which of the following immunologic
mechanisms is of primary importance in the pathogenesis of
her disease?
A Activation of neutrophils and macrophages by IL-8
B Chemoattraction of eosinophils by exotoxin
C Proliferation of the TH2 subset of CD4+ T cells
D Recruitment of monocytes by interferon-γ
E Stimulation of bronchial smooth muscle cells by
ADAM-33
464
4 A 26-year-old, previously healthy woman has developed C H A P T E R 3 0 Final Review and Assessment 4 6 5
fever and generalized diffuse erythematous macular rash resem-
bling sunburn in the past day. Her menstrual cycles are regular. 7 A 70-year-old man has had memory loss and decreased
She has nausea, vomiting, abdominal pain, diarrhea, myalgias, ability to perform activities of daily living for the past 2 years.
sore throat, headache, and dizziness. On physical examination, He has increasing exercise intolerance and difficulty breathing
her temperature is 39.4° C, pulse is 101/min, respirations are for the past year. On physical examination, with auscultation of
23/min, and blood pressure is 90/40 mm Hg. She has oropha- the chest, rales are audible in the lung bases, and there is a dia-
ryngeal and conjunctival hyperemia. The vaginal mucosa is stolic murmur. He has a marked decrease in sensation to light
erythematous. A tampon is present in the vaginal vault. She is touch and pinprick over the lower extremities. His gait is ataxic,
disoriented, but there are no focal neurologic deficits. Laboratory with the feet widely spaced. He cannot name any of three ob-
findings show hemoglobin, 13.5 g/dL; hematocrit, 41.4%; platelet jects after 3 minutes. He thinks he is an astronaut returned from
count, 100,000/mm3; WBC count, 13,200/mm3; glucose, 70 mg/ Mars. An echocardiogram shows aortic regurgitation with a
dL; creatinine, 2.5 mg/dL; total bilirubin, 2.4 mg/dL; AST, 82 widened aortic root and arch. MRI of the brain shows mild dif-
U/L; and ALT, 29 U/L. She receives nafcillin with clindamycin fuse cortical atrophy and meningeal thickening. Infection with
and improves, but skin and mucous membrane desquamation what organism would most likely produce these findings?
is noted 10 days later. These findings are most likely produced A Borrelia burgdorferi
by a toxin elaborated by which of the following organisms? B Coxsackievirus B
A Bacillus anthracis C HIV
B Clostridium perfringens D Mycobacterium leprae
C Enterococcus E Mycobacterium tuberculosis
D Listeria monocytogenes F Treponema pallidum
E Staphylococcus aureus G West Nile virus
F Vibrio vulnificus
8 A 19-year-old woman has sudden onset of severe abdomi-
5 A 19-year-old man is found unconscious and taken to nal and back pain and dyspnea. She has had similar episodes
the emergency department. On physical examination, his tem- over a 12-year period. She had osteomyelitis of the left hip 1
perature is 41.2° C, pulse is 103/min, respirations are 27/min year ago; the bone culture was positive for Salmonella enteritidis.
and shallow, and blood pressure is 145/100 mm Hg. He devel- On physical examination, she has tachycardia. Palpation of the
ops an intractable cardiac dysrhythmia and dies. At autopsy, abdomen reveals diffuse tenderness with rigidity of abdominal
the heart is slightly enlarged; microscopically, the distal coro- musculature, but no apparent masses. CT scan of the chest shows
nary arteries are thickened. Sections of the brain show a 2-cm prominent pulmonary veins, but no infiltrates. Abdominal CT
area of hemorrhage in the right superior parietal lobe and a scan shows the presence of multiple 0.5- to 1-cm stones in the
0.5-cm hemorrhage in the medulla. There is a partially cystic, gallbladder, a very small spleen, and prominent hepatic veins.
1-cm area with brown discoloration in the left anterior frontal CBC shows hemoglobin of 10.2 g/dL, hematocrit of 30.9%, MCV
lobe. This clinical picture is most likely to have developed by of 99 μm3, RDW of 22, platelet count of 189,300/mm3, and WBC
usage of which of the following substances? count of 6320/mm3. What additional laboratory test finding is
A Barbiturate most likely in this case?
B Cocaine A Amylase, 694 U/L
C Ethanol B Anticardiolipin antibody
D Heroin C Calcium, 12.3 mg/dL
E Marijuana D Cholesterol, 250 mg/dL
F Methamphetamine E Haptoglobin, 1 mg/dL
G Phencyclidine F Triglyceride, 1140 mg/dL
6 A 49-year-old man has had increasing knee and hip pain 9 A 49-year-old man seeks a prescription for erectile dys-
for the past 10 years. The pain is worse at the end of the day. function. He is 168 cm (5 feet 6 inches) tall and weighs 93 kg
During the past year, he has become increasingly drowsy at (body mass index 33). On physical examination, there are bi-
work. His wife complains that he is a “world class” snorer. lateral carotid bruits and a midline palpable abdominal pulsa-
During the past month, he has experienced bouts of sharp, col- tile mass. Decreased hair is noted over the lower extremities,
icky, right upper abdominal pain. On physical examination, and a 1-cm shallow ulceration is present in the skin over the
his temperature is 37° C, pulse is 82/min, respirations are 10/ right first metatarsal head. He has decreased sensation to light
min, and blood pressure is 140/85 mm Hg. He is 175 cm (5 touch and pinprick in the lower extremities. Laboratory find-
feet 8 inches) tall and weighs 156 kg (body mass index 51). ings include hemoglobin, 12.9 g/dL; hematocrit, 42%; WBC
Laboratory findings show glucose of 139 mg/dL, Hb A1c of count, 8950/mm3; and creatinine, 1.7 mg/dL. Which of the
10, total cholesterol of 229 mg/dL, and HDL cholesterol of 33 following laboratory findings is most likely to be present in
mg/dL. An arterial blood gas measurement shows pH of 7.35; this man?
Pco2, 50 mm Hg; and Po2, 75 mm Hg. Which of the following A Oligoclonal IgG bands in CSF
additional conditions is most likely present in this man? B Hemoglobin A1c, 8.8%
A Hashimoto thyroiditis C Plasma ACTH, 119 pg/mL
B Hypertrophic cardiomyopathy D Plasma homocysteine, 23 μmol/L
C Laryngeal papillomatosis E Serum anti–parietal cell antibodies
D Nonalcoholic fatty liver disease
E Panlobular emphysema
F Rheumatoid arthritis
4 6 6 U N I T I I Diseases of Organ Systems 12 A 46-year-old Welsh man has had worsening arthritis in-
volving his hands, knees, hips, and elbows for the past 3 years.
10 A 10-month-old infant is not meeting developmental He has had increasing orthopnea and worsening pedal edema
milestones and is below ideal weight and height. The parents for the past year. On physical examination, he has decreased
noted an episode of convulsions 1 week ago. On physical ex- range of motion of the lower legs, but no apparent joint de-
amination, the infant has hepatosplenomegaly and general- formities, warmth, or swelling. There is a b rownish hue to his
ized nontender lymphadenopathy. There is tenderness on skin, although he rarely goes outdoors. Laboratory findings
palpation of the right upper extremity. No focal neurologic show hemoglobin, 13.7 g/dL; hematocrit, 40.8%; MCV, 90 μm3;
deficits are present, but the infant’s attention and movement platelet count, 213,500/mm3; WBC count, 6690/mm3; glucose,
are diminished. A radiograph of the right arm shows a heal- 201 mg/dL; creatinine, 1.2 mg/dL; and calcium, 8.2 mg/dL. A
ing fracture. Laboratory findings show hemoglobin of 9.7 g/ mutation in a gene encoding for which of the following most
dL, hematocrit of 28.4%, platelet count of 76,700/mm3, WBC likely explains these findings?
count of 4200/mm3, glucose of 78 mg/dL, and creatinine of 0.4 A B-globin
mg/dL. A bone marrow biopsy is done and the microscopic B Glucokinase
appearance is shown in the figure. The infant is most likely to C LDL receptor
have the near absence of which of the following enzymes? D HFE
A α-l-Iduronidase E TNF
B α-1,4-Glucosidase
C Arylsulfatase A 13 A 33-year-old woman has had increasing lethargy and
D Glucocerebrosidase sensitivity to sunlight for the past 8 month. She has pain in
E Hexosaminidase A her hands, elbows, knees, and feet, and muscle aches in her
F Sphingomyelinase arms and legs. She has had increasing dyspnea for the past
11 A 54-year-old man has had nausea for the past 6 months, week. Physical examination shows no joint deformities, swell-
but he does not report hematemesis. He has increasing mal- ing, or redness. On auscultation of the chest, a friction rub is
aise. On physical examination, he has decreased sensation to audible. A chest radiograph shows bilateral pleural effusions.
pinprick and light touch over the lower extremities bilaterally. Laboratory findings show hemoglobin, 11.6 mg/dL; hemato-
He exhibits mild ataxia when walking. An upper gastrointesti- crit, 34.3%; MCV, 84 μm3; platelet count, 133,400/mm3; WBC
nal endoscopy study shows the absence of gastric rugal folds, count, 4610/mm3; glucose, 80 mg/dL; creatinine, 2.4 mg/dL;
but no ulceration or mass. Which of the following findings is and calcium, 7.9 mg/dL. Which of the following additional
most likely to be detected on further work up? laboratory tests would be most helpful to diagnose her under-
A Positive anti-Smith antibody lying condition?
B Deficiency of factor V A Anti–acetylcholine receptor antibody
C Positive Helicobacter pylori antibody B Anti–DNA topoisomerase antibody
D MCV 125 μm3 C Anti–glomerular basement membrane antibody
E Urine glucose 4+ D Antimicrosomal antibody
E Antimitochondrial antibody
F Antinuclear antibody
14 A 31-year-old woman has had a persistent fever for the
past 2 months. Her temperature has ranged from 38.3° C to
38.6° C on multiple occasions. On physical examination, she
has diffuse abdominal pain and mild splenomegaly, but no
hepatomegaly or lymphadenopathy. Laboratory studies show
Hgb, 13.2 g/dL; Hct, 39.8%; MCV, 930 μm3; platelet count,
242,000/mm3; and WBC count, 12,290/mm3 with 71% seg-
mented neutrophils, 19% lymphocytes, and 10% monocytes.
CT imaging of her abdomen shows an ill-defined pelvic soft-
tissue density mass with a mottled lucent center and a small,
square, radiopaque area. Review of her medical record reveals
that a salpingo-oophorectomy for ectopic pregnancy was per-
formed on the left side 3 months ago. Which of the following
is the most likely cause of her persistent fever?
A Abscess
B Non-Hodgkin lymphoma
C Ovarian cystadenocarcinoma
D Sarcoidosis
E Pelvic inflammatory disease
15 A 52-year-old woman has a 3-month history of fatigue C H A P T E R 3 0 Final Review and Assessment 4 6 7
on exertion, dizziness, and syncopal episodes. She has trou-
ble keeping her eyes open toward the end of the day and has 17 A 58-year-old man has noticed increasing abdominal
double vision. On physical examination, she is afebrile and girth and decreased libido for the past 7 months. Physical
exhibits marked pallor, but no hepatosplenomegaly or lymph- examination shows an enlarged abdomen with a fluid wave,
adenopathy. There is decreased motor strength with repetitive but no tenderness or masses; the spleen tip is palpable. Bibasi-
motion, but no apparent muscle atrophy, joint deformity, pain, lar crackles are audible on auscultation of the chest. There is
or redness. Laboratory findings show hemoglobin of 6.6 g/ 1+ pitting edema to the knees. The testes are smaller than
dL, hematocrit of 19.9%, platelet count of 199,800/mm3, WBC normal, but without masses. Laboratory findings show hemo-
count of 4780/mm3, and reticulocyte count of 0.1%. A bone globin, 12.2 g/dL; hematocrit, 36.9%; MCV, 103 μm3; platelet
marrow biopsy specimen shows markedly reduced erythro- count, 189,400/mm3; WBC count, 5762/mm3; creatinine, 1.1
poiesis. The figure shows a chest CT scan. Which of the follow- mg/dL; glucose, 88 mg/dL; total protein, 5.7 g/dL; albumin,
ing serologic laboratory tests is most likely to be found in this 2.7 g/dL; AST, 167 U/L; ALT, 69 U/L; alkaline phosphatase,
woman? 48 U/L; total bilirubin, 1.5 mg/dL; and prothrombin time, 23
A Anti–acetylcholine receptor antibody seconds. What is the most likely diagnosis?
B Anti–DNA topoisomerase A Adrenal atrophy
C Anti–glomerular basement membrane antibody B Aortic valvular stenosis
D Antimitochondrial antibody C Autoimmune gastritis
E Antinuclear antibody D Chronic glomerulonephritis
E Hypertrophic cardiomyopathy
16 A 24-year-old, previously healthy man has developed F Micronodular cirrhosis
a cough with bloody sputum along with decreased output
of dark urine over the past 2 days. He smokes one pack of 18 A 72-year-old woman with chronic bronchitis from ciga-
cigarettes per day and works as a histotechnologist. A chest rette smoking has been bedridden for the past 2 weeks. She
radiograph shows diffuse infiltrates most pronounced in the experiences sudden, severe dyspnea with chest pain. On ex-
lower lobes. Laboratory findings show hemoglobin, 13.7 g/ amination, her temperature is 37° C, pulse is 104/min, respira-
dL; hematocrit, 40.6%; MCV, 91 μm3; platelet count, 361,000/ tory rate is 31/min, and blood pressure is 100/60 mm Hg. Her
mm3; WBC count, 7385/mm3; creatinine, 3.8 mg/dL; urea left leg is swollen and painful on raising. She appears cyanotic.
nitrogen, 36 mg/dL; and glucose, 75 mg/dL. An abdominal A systolic ejection sound and diastolic murmur are auscul-
ultrasound scan shows normal-sized kidneys. A renal biopsy tated over the pulmonic region. A chest radiograph shows a
specimen shows a crescentic glomerulonephritis. Which of the prominent right border of the heart. Laboratory studies show
following pathologic mechanisms most likely produced this an elevated D-dimer level. She then develops right leg weak-
patient’s pulmonary disease? ness. MRI of the brain shows early infarction within the left
A Antibody directed against basement membrane hemisphere. Which of the following cardiac conditions best
explains these findings?
collagen A Constrictive pericarditis
B Apoptosis induced by CD8+ lymphocytes B Dilated cardiomyopathy
C Complement activation by circulating antigen- C Ventricular septal defect
D Infective endocarditis
antibody complexes E Rheumatic heart disease
D Macrophage activation by CD4+ lymphocytes
E Release of inflammatory mediators from mast cells 19 A 24-year-old woman has developed right-sided fa-
cial pain over the past 24 hours. She has experienced a 5-kg
weight loss over the past 6 months, despite increasing ca-
loric intake. On physical examination, there is swelling with
marked tenderness over the right maxilla, exophthalmos on
the right side, diffuse abdominal pain, poor skin turgor, and
dry mucous membranes. Her temperature is 37.7° C. She has
tachycardia, but no murmurs, and tachypnea; the lung fields
are clear. Laboratory findings show Na+, 131 mmol/L; K+, 4.6
mmol/L; Cl–, 92 mmol/L; CO2, 9 mmol/L; glucose, 481 mg/
dL; and creatinine, 1 mg/dL. An arterial blood gas measure-
ment shows pH, 7.2; Po2, 98 mm Hg; Pco2, 28 mm Hg; and
HCO3–, 10 mmol/L. Fine-needle aspiration of the right maxil-
lary region is performed. What organism is most likely to be
present in this aspirate?
A Actinomyces israelii
B Bacillus anthracis
C Cytomegalovirus
D Clostridium perfringens
E Cryptococcus neoformans
F Mucor circinelloides
4 6 8 U N I T I I Diseases of Organ Systems 23 A 52-year-old man has a 20-year history of Crohn dis-
ease. Over the past 14 months, he has had increasing fatigue
20 A 31-year-old man has an infertility work-up. He has with worsening peripheral edema. On physical examina-
aspermia. He also has chronic diarrhea with elevated quanti- tion, he has pitting edema to his knees. Laboratory studies
tative stool fat. He has had recurrent, severe respiratory tract show serum urea nitrogen is 35 mg/dL and creatinine is 3.8
infections since early childhood. As a neonate, he had bowel mg/dL. Urinalysis shows proteinuria without hematuria,
obstruction from meconium ileus. He is most likely to have glucosuria, or ketonuria. A renal biopsy specimen shows
an abnormality involving mutation in which of the following deposits of amorphous pink material in glomeruli, arteri-
genes? oles, and peritubular interstitium. By electron microscopy,
A CFTR these pink deposits are composed of nonbranching 7.5- to
B FGFR 10-nm fibrils. Which of the following proteins is most likely
C G6PD to form these fibrils?
D HFE A Amyloid-associated
E NF1 B Atrial natriuretic peptide
F p53 C β2-Microglobulin
D Calcitonin
21 Children 6 to 10 years old in the same community are E Lambda light chain
observed by the local physician to be doing poorly in school, F Transthyretin
which has been attributed to behavioral problems. Their par-
ents state that these children have poor appetites, complain of 24 A 40-year-old man has been bothered by oral candi-
nausea, and have frequent headaches. On physical examina- diasis, fever, and diarrhea for the past year. On physical
tion, they have decreased sensation to touch over the lower examination, he has muscle wasting. His weight is 70% of nor-
extremities. They exhibit loss of fine motor control of move- mal for his height and age. He has generalized nontender
ment and have a slightly ataxic gait. A representative CBC lymphadenopathy, but no hepatosplenomegaly. He devel-
shows hemoglobin of 11.8 g/dL, hematocrit of 35.2%, MCV oped three irregular, 1- to 2-cm, reddish-purple, nodular
of 82 μm3, platelet count of 282,300/mm3, and WBC count of skin lesions on his forearm in the past 3 months. Laboratory
4745/mm3. Examination of the peripheral blood smear shows findings show hemoglobin, 12.2 g/dL; hematocrit, 36.5%;
basophilic stippling of the RBCs. Excessive chronic ingestion MCV, 85 μm3; platelet count, 188,000/mm3; and WBC count,
of which of the following substances is most likely to explain 2460/mm3 with 82% segmented neutrophils, 4% bands, 6%
these findings? lymphocytes, 6% monocytes, and 2% eosinophils. Infection
A Cadmium with which of the following organisms is most likely to pro-
B Copper duce these findings?
C Iron A Hepatitis C virus
D Lead B Herpes simplex virus
E Nickel C HIV
D Mycobacterium leprae
22 A 45-year-old, previously healthy woman has had a E Staphylococcus aureus
chronic nonproductive cough for the past 2 months. One week F Streptococcus pyogenes
ago, her cough was productive of blood-streaked sputum. She
does not smoke. Physical examination shows temperature of 25 A 30-year-old man has noted joint pain in the right hip
37.5° C and blood pressure of 140/90 mm Hg. On ausculta- and left elbow and a headache for the past week. One month
tion, bilateral crackles are audible in the lungs. A chest ra- ago, he had similar pain in the left hip and knee, which slowly
diograph shows bilateral nodular and cavitary infiltrates, but resolved. He remembers having a ringlike skin rash on his left
there are no masses. Laboratory findings show hemoglobin, thigh that developed 4 months ago after a camping trip in the
11.7 g/dL; hematocrit, 35.2%; platelet count, 217,000/mm3; woods in Connecticut. On physical examination, there is joint
WBC count, 6330/mm3; serum glucose, 72 mg/dL; creatinine, tenderness, but no swelling or deformity of the right hip and
2.6 mg/dL; and urea nitrogen, 25 mg/dL. Urinalysis shows 1+ left elbow. His heart rate is slightly irregular. What infectious
proteinuria, 2+ hematuria, and no glucose or ketones. A trans- agent is most likely to produce these findings?
bronchial biopsy specimen shows necrotizing granulomatous A Borrelia burgdorferi
vasculitis of the alveolar capillaries and small peripheral pul- B Mycobacterium tuberculosis
monary arteries. A renal biopsy specimen shows a crescentic C Streptococcus pyogenes
glomerulonephritis. Which of the following serologic test re- D Staphylococcus aureus
sults is most likely to be positive in this woman? E Yersinia enterocolitica
A Anti–DNA topoisomerase I antibody
B Anti–glomerular basement membrane antibody
C Anti–Jo-1 antibody
D Antimitochondrial antibody
E Anti–neutrophil cytoplasmic autoantibody
F Anti–double stranded DNA antibody
G Antiribonucleoprotein antibody
C H A P T E R 3 0 Final Review and Assessment 4 6 9
phosphatase, 80 U/L; total bilirubin, 4 mg/dL; and direct
bilirubin, 3.1 mg/dL. Serologic test results are positive for anti-
HCV and negative for anti-HBs and IgM anti-HAV. Urinalysis
shows 4+ proteinuria and 1+ hematuria. CT scan of the abdo-
men shows a small amount of ascites, mild hepatomegaly, and
no splenomegaly or lymphadenopathy. A biopsy specimen of
an ulcerated skin lesion shows leukocytoclastic vasculitis
involving the upper dermis. What is the most likely diagnosis?
A Autoimmune hemolytic anemia
B Hepatocellular carcinoma
C Hereditary hemochromatosis
D Mixed cryoglobulinemia
E Multiple myeloma
26 A 63-year-old man has become more withdrawn, less talk- 29 A 22-year-old woman incurs multiple blunt trauma with
ative, and less active over the past 3 years. He now spends most bilateral femoral and right humeral fractures from a fall. The
of his day in bed, although he has minimal difficulty with move- fractures are treated with open reduction and internal fixation.
ment. On physical examination, he has 5/5 motor strength in all She is in stable condition until 3 days later, when she becomes
extremities; there is no apparent tremor or ataxia. There are no fo- progressively delirious and then comatose. On physical ex-
cal neurologic deficits. He can remember only one of three objects amination, she is afebrile. Head CT scan shows generalized
after 3 minutes. His mood is depressed. His condition improves brain edema. The representative gross appearance of her brain
with use of an acetylcholinesterase inhibitor. One year later, he is shown in the figure. Lumbar puncture yields clear CSF with
has an episode of aspiration while eating and dies 1 week later no RBCs, one mononuclear cell, and normal protein and glu-
of pneumonia. At autopsy, the brain weighs 1000 g. The gross cose. Her serum glucose is 102 mg/dL, and creatinine is 0.9
appearance is shown in the figure. Which of the following micro- mg/dL. What is the most likely diagnosis?
scopic findings is most likely to be seen in the frontal cortex? A Central pontine myelinolysis
A Aβ amyloid deposits B Diffuse axonal injury
B Absence of Betz cells C Fat embolism
C Alzheimer type II cells D Ruptured berry aneurysm
D Arteriolosclerosis E Staphylococcus aureus abscesses
E Red neurons F Viral meningitis
F Spongiform change
30 A translational research project is focused on develop-
27 A 51-year-old man has had increasing lethargy over ment of a pharmacologic agent that would affect molecular sig-
the past year. On physical examination, his blood pressure is naling pathways within cells. This agent binds to type 1 TNF
165/100 mm Hg. He has deformity and decreased range of receptor (TNFR1), which triggers activation of intracellular cas-
motion of the first three metacarpophalangeal (MCP) joints on pases. For what condition is this agent most likely to be useful?
the right and the second two MCP joints on the left. There is A Adenocarcinoma
a 2-cm firm, painless nodule over the left olecranon bursa. A B Atherosclerosis
similar 1-cm nodule is palpated in the helix of the right ear, C Bronchiectasis
and another 1.5-cm nodule is palpable over the right Achil- D Cirrhosis
les tendon. Urinalysis shows specific gravity of 1.012, pH 5.5, E Dementia
1+ hematuria, 1+ proteinuria, and no glucose. The serum urea F Osteoporosis
nitrogen level is 31 mg/dL, and the creatinine is 3.2 mg/dL.
Aspiration of material from the nodule at the left elbow is per-
formed. Which of the following types of crystals is most likely
to be seen microscopically in this aspirate?
A Calcium pyrophosphate dihydrate
B Cholesterol
C Cystine
D Hydroxyapatite
E Sodium urate
28 A 38-year-old woman has had malaise and arthral-
gias for the past 14 months. On physical examination, she
has scleral icterus and 1- to 3-cm areas of reddish-purple
discoloration on her skin. Several of these areas show focal
ulceration. Laboratory findings show total protein, 7.1 g/dL;
albumin, 3.3 g/dL; AST, 127 U/L; ALT, 145 U/L; alkaline
4 7 0 U N I T I I Diseases of Organ Systems
33 A 22-year-old woman is diagnosed with bipolar dis-
order. Over the next year, she develops neurologic manifes-
tations that include resting and intention tremors, rigidity,
chorea, dysphagia, and dysarthria. On physical examination,
she has bilateral Babinski signs. There are ringlike deposits of
green material involving the cornea bilaterally, but her vision
is not decreased. One year later, she has an illness that lasts 3
weeks, with nausea, vomiting, and malaise and scleral icterus.
Laboratory findings include serum AST, 100 U/L; ALT, 122
U/L; alkaline phosphatase, 105 U/L; total bilirubin, 4.5 mg/
dL; glucose, 77 mg/dL; and creatinine, 0.9 mg/dL. Serologic
test results for hepatitis A, B, and C are negative. This episode
subsides without treatment, but she eventually develops cir-
rhosis. A mutation in a gene encoding for what substance is
most likely to be present in this woman?
A α1-Antitrypsin
B CFTR
C Copper-transporting ATPase
D Galactose-1-phosphate uridyltransferase
E Glucocerebrosidase
F Glucose-6-phosphatase
31 A 32-year-old woman has noticed a decline in dexterity 34 A 57-year-old woman experiences a sudden loss of con-
and strength of her right hand in her work as an auto mechan- sciousness. She has a history of untreated hypertension, and
ic for the past 2 years. She experienced painful burning sensa- has smoked one pack of cigarettes per day for the past 40
tions in the left upper extremity 1 year ago. She had an episode years. On physical examination, her temperature is 37.1° C,
of decreased visual acuity in the left eye lasting 3 days. She pulse is 70/min and irregular, respirations are 18/min, and
is insensitive to heat. On physical examination, she is afebrile blood pressure is 90/40 mm Hg. Carotid and radial pulses are
and her blood pressure is normal. Motor strength in the right diminished compared with femoral and posterior tibial puls-
extremity is 4/5, but 5/5 elsewhere. Vision is 20/100 in the es. Auscultation of the chest reveals faint heart sounds; lung
left eye and 20/40 in the right eye. One year later, she reports fields are clear. A chest radiograph shows a widened medias-
chronic constipation and incontinence. A magnetic resonance tinum. The chest CT scan with contrast is shown in the figure.
image of her brain is shown in the figure. What is the most Pericardiocentesis is performed, and there is blood in the aspi-
likely diagnosis? rate. What condition is most likely to produce these findings?
A Diabetes mellitus A Aortic dissection
B Graves disease B Bicuspid aortic valve
C HIV infection C Small cell anaplastic carcinoma
D Multiple sclerosis D Takayasu arteritis
E Myasthenia gravis E Tertiary syphilis
F Systemic lupus erythematosus F Thromboangiitis obliterans
32 A 32-year-old woman whose pregnancy was uncom-
plicated gives birth at term. A newborn physical examination
shows a small lower lumbar skin dimple with a protruding tuft
of hair. A radiograph shows that the underlying L4 vertebra
has lack of closure of the posterior arches. What is the most
likely diagnosis?
A Arnold-Chiari malformation
B Dandy-Walker malformation
C Meningomyelocele
D Spina bifida occulta
E Tuberous sclerosis
35 A 62-year-old woman has had a chronic cough and in- C H A P T E R 3 0 Final Review and Assessment 4 7 1
creasing dyspnea for 10 years. A chest radiograph performed fissures are oblique. He has brachycephaly. On auscultation
1 year ago showed increased lucency of upper lung fields of the chest, a holosystolic murmur is audible. During child-
and bilateral flattening of the diaphragmatic leaves. She has hood, intellectual disability is exhibited, but the child is able
had nausea and vague abdominal discomfort for 6 months. to perform activities of daily living. At age 17 years, the boy
Biopsy specimens from an upper gastrointestinal endoscopic has a series of severe upper respiratory tract infections. CBC
study show a chronic nonspecific gastritis with no detectable shows hemoglobin, 10.2 g/dL; hematocrit, 30.5%; MCV, 89
Helicobacter pylori organisms. During the past month, she has μm3; platelet count, 103,000/mm3; and WBC count, 19,200/
passed red urine on several occasions. Cystoscopic examina- mm3 with 14% segmented neutrophils, 6% bands, 22% lym-
tion shows a 3-cm exophytic mass in the dome of the bladder, phocytes, 13% monocytes, and 45% blasts. What karyotype is
and biopsy specimens show a urothelial carcinoma. What is most likely to be present in this boy?
her most likely risk factor for this spectrum of findings? A 45,X
A α1-Antitrypsin deficiency B 46,XY
B Chronic alcoholism C 47,XY,13
C Cigarette smoking D 47,XY,18
D Exposure to aniline dye E 47,XY,21
E Vitamin C deficiency F 47,XXY
36 A 42-year-old woman has had increasing weakness,
nausea, vomiting, watery diarrhea, and a 5-kg weight loss 39 A 52-year-old woman has noticed increasing thirst and
over the past 7 months. She has generalized muscle weakness, urine output for the past 6 months. She has had flank pain
muscle wasting, and increased skin pigmentation on physical on the right during the past month. On physical examina-
examination. After an upper respiratory tract infection lasting tion, her temperature is 37° C, pulse is 77/min, respirations
1 week, she develops abdominal pain and faintness and lapses are 14/min, and blood pressure is 150/95 mm Hg. There are
into a coma. Her temperature is 36.9° C, pulse is 83/min, res- bilateral palpable masses in the abdomen. The figure shows
pirations are 17/min and shallow, and blood pressure is 80/40 her abdominal CT scan. Urinalysis shows specific gravity of
mm Hg. Laboratory findings show Na+, 129 mmol/L; K+, 3.5 1.010, pH 6.5, 2+ proteinuria, 2+ hematuria, and no glucose
mmol/L; Cl−, 95 mmol/L; CO2, 23 mmol/L; glucose, 48 mg/ or ketones. Laboratory findings show hemoglobin of 10.4 g/
dL; and creatinine, 0.6 mg/dL. Atrophy of which of the fol- dL, hematocrit of 31.3%, glucose of 102 mg/dL, creatinine of
lowing tissues is most likely to be present? 5.5 mg/dL, and urea nitrogen of 53 mg/dL. One year later,
A Adrenal cortex she develops a sudden, severe headache. CT scan of the head
B Hypothalamus shows a subarachnoid hemorrhage at the base of the brain.
C Islets of Langerhans What is the most likely diagnosis?
D Parafollicular C cells in thyroid A Adult-onset medullary cystic disease
E Pineal gland B ANCA-associated granulomatous vasculitis
F Thyroid epithelium C Autosomal dominant polycystic kidney disease
D Cystinosis
37 A 39-year-old man has experienced diminished libido E Type 2 diabetes mellitus
for the past 4 months. Review of systems indicates that he has F Polyarteritis nodosa, classic type
had frequent headaches over the past 2 months. On physical
examination, he is normotensive, has gynecomastia bilaterally,
has normal-sized testes in the scrotum, and exhibits difficulty
with peripheral vision. His visual acuity is 20/20 bilaterally.
Laboratory findings show Na+, 141 mmol/L; K+, 4.1 mmol/L;
Cl–, 102 mmol/L; CO2, 25 mmol/L; glucose, 75 mg/dL; and
creatinine, 1.2 mg/dL. Which of the following neoplasms is he
most likely to have?
A Prolactinoma
B Carcinoid tumor
C Medullary carcinoma
D Pheochromocytoma
E Renal cell carcinoma
F Small cell anaplastic carcinoma
38 A boy infant is born to a 41-year-old woman following
an uncomplicated pregnancy. He is noted at birth to be at the
70th percentile for height and weight. On physical examina-
tion, the infant has bilateral palmar transverse creases and
absent distal flexion creases on the fifth digits. The palpebral
4 7 2 U N I T I I Diseases of Organ Systems 43 A 26-year-old, previously healthy man sustains blunt
force trauma to the left upper arm. On physical examination,
40 A 13-year-old girl has been in foster care with 10 care- there is focal swelling and redness. Three weeks later, the
givers for the past 11 years. On physical examination, there are superficial contusion has resolved, but now a slightly tender
ecchymoses of the trunk, extremities, and gingivae. A hyper- mass is palpated in the outer aspect of the upper left arm. A
keratotic, papular rash, with 0.4-cm lesions ringed by hemor- radiograph of the left arm shows a 5-cm mass in the soft tis-
rhage, is present in a similar distribution. The child has pain sue. There is a radiolucent center and surrounding irregular
on movement of the arms and legs. There is abnormal depres- bone formation. One month later, the mass is now 3 cm and
sion of the sternum with prominence of the ribs and the cos- painless. CT scan of the arm shows a well-circumscribed mass
tochondral junctions. Radiographs of the arms and legs show within muscle with areas of bright calcification throughout.
bowing of the long bones and widening of the metaphyses, What is the most likely diagnosis?
with normal calcification. There is a right femoral subperios- A Gouty tophus
teal hematoma. No fractures are noted. CBC shows hemoglo- B Hemarthrosis
bin of 10.8 g/dL, hematocrit of 32.4%, MCV of 77 μm3, platelet C Myositis ossificans
count of 201,300/mm3, and WBC count of 5730/mm3. She is D Osteochondroma
most likely to have a metabolic defect involving which of the E Osteosarcoma
following? F Polymyositis
A Carbonic anhydrase levels
B Factor VIII activity
C Fibroblast growth factor receptor 44 A 35-year-old man has had bouts of severe, diffuse ab-
D Hydroxylation of collagen dominal pain accompanied by fever, malaise, and myalgias
E Vitamin D synthesis over the past 4 months. On physical examination, his tempera-
F Scurvy ture is 37.7° C, pulse is 81/min, respirations are 20/min, and
blood pressure is 145/90 mm Hg. There is diffuse abdominal
41 An 11-year-old girl has a respiratory tract infection and tenderness, but no masses, and bowel sounds are present. A
is treated with trimethoprim-sulfamethoxazole. Three days stool sample is positive for occult blood. Laboratory findings
later, she develops a sore throat, malaise, fever, and a macular show serum glucose of 73 mg/dL, amylase of 44 U/L, AST of 54
skin rash on the trunk and extremities. Some of the skin le- U/L, ALT of 23 U/L, creatinine of 2.4 mg/dL, and urea nitrogen
sions have a central raised area of more pronounced erythema. of 22 mg/dL. A renal biopsy specimen shows acute transmural
Within 4 days, there are erosions of the oral mucosa and small vasculitis of medium-sized arteries; the glomeruli and tubules
blisters developing on purpuric skin macules. The blisters en- are unremarkable. Mesenteric artery angiography is performed
large slightly and then show epidermal detachment. The total with the appearance shown in the figure. Which of the following
body surface area involved with blistering and detachment serologic tests is most likely to be positive in this man?
is less than 10%. The occurrence of cutaneous lesions is most A Antimitochondrial antibody
likely mediated by which of the following cell types? B ANA
A CD8+ lymphocytes C C-ANCA
B Eosinophils D Cryptococcus neoformans antigen
C Langerhans cells E HbsAg
D Macrophages F Histoplasma capsulatum antibody
E Neutrophils
F Natural killer cells
42 A 21-month-old child has had recurrent otitis media com-
plicated by mastoiditis for the past 3 months. On physical ex-
amination, there is a seborrheic eruption on the skin of the trunk
and scalp. Hepatosplenomegaly and generalized nontender
lymphadenopathy are present. A chest radiograph shows bi-
lateral 0.5- to 2-cm pulmonary nodules, and there is a 1-cm le-
sion on the right clavicle and a 1.5-cm lesion on the left seventh
rib, both osteolytic. Laboratory findings show pancytopenia. A
bone marrow biopsy specimen shows reduced hematopoiesis
with an increased number of large cells having oval vesicular
nuclei and vacuolated cytoplasm that mark immunocytologi-
cally for CD1a. What is the most likely diagnosis?
A Acute lymphoblastic leukemia
B Gaucher disease
C Langerhans cell histiocytosis
D Leishmaniasis
E Multiple myeloma
F Myelodysplastic syndrome
45 A 4-year-old girl has become increasingly listless over C H A P T E R 3 0 Final Review and Assessment 4 7 3
the past year. She is at the 25th percentile for height and
weight. On physical examination, there is pubic hair and cli- menstruate. She is given a dopamine agonist and improves.
toral and breast enlargement. There is no hepatomegaly, sple- Laboratory findings show calcium, 11.1 mg/dL; phosphorus,
nomegaly, or lymphadenopathy. The neurologic examination 2.4 mg/dL; and creatinine, 1.1 mg/dL. Which of the following
is unremarkable. Laboratory findings show hemoglobin, 13.7 gene mutations and associated neoplasm is characteristic of
g/dL; hematocrit, 41.8%; WBC count, 7120/mm3; Na+, 128 this disorder?
mmol/L; K+, 4.8 mmol/L; Cl−, 99 mmol/L; CO2, 21 mmol/L; A MEN1—Islet cell adenoma
glucose, 69 mg/dL; creatinine, 0.5 mg/dL, and ACTH of 95 B RET—Medullary carcinoma
pg/mL with loss of diurnal rhythm of secretion. What disease C BCL6—Non-Hodgkin lymphoma
process is most likely associated with these findings? D APC—Osteoma
A Adrenal cortical hyperplasia E RET—Pheochromocytoma
B Islet cell adenoma F VHL—Renal cell carcinoma
C Pituitary microadenoma
D Retroperitoneal neuroblastoma 48 A 60-year-old man has had worsening dyspnea and
E Suprasellar craniopharyngioma nonproductive cough over the past 2 years. On physical ex-
F Thyroid medullary carcinoma amination, his temperature is 37.4° C, pulse is 74/min, respi-
rations are 20/min, and blood pressure is 110/70 mm Hg. A
chest radiograph shows extensive interstitial lung disease and
46 A 39-year-old man has had a 4-kg weight loss with wa- a prominent right-sided heart border. Spirometry reveals de-
tery diarrhea and flatulence over the past 8 months. He has creased FEV1 and FVC. His pulmonary disease is most likely
had urticarial plaques on extensor surfaces of the elbows and caused by exposure to which of the following?
knees and on the upper back for the past month. Some of the A Carbon monoxide
plaques have small, grouped vesicles. A biopsy specimen of B Fungal hyphae
one of the skin lesions shows neutrophils at the tips of dermal C Plant pollen
papillae with overlying basal cell vacuolization. Under immu- D Silica crystals
nofluorescence microscopy, granular IgA deposits appear at E Sulfur dioxide
the tips of dermal papillae. The figure shows the microscopic F Wood dusts
appearance of a jejunal biopsy specimen. More than 20 years
later, he develops a T-cell lymphoma of the jejunum. Serologic 49 A 42-year-old man has noticed worsening myalgias and
studies are most likely to reveal antibodies against which of increasing difficulty swallowing over the past 2 years. When
the following molecules? exposed to cold, the skin of his hands turns white. On physical
A Desmoglein 3 examination, he has an erythematous rash extending across
B Double-stranded DNA the bridge of his nose. There is swelling and warmth in the
C Cyclic citrullinated peptide joints of his hands. Laboratory findings show hemoglobin,
D Histone 12.2 g/dL; hematocrit, 36.5%; platelet count, 180,000/mm3;
E Ribonucleoprotein WBC count, 4510/mm3; serum glucose, 72 mg/dL; total bili-
F Tissue transglutaminase rubin, 1 mg/dL; AST, 41 U/L; ALT, 19 U/L; alkaline phos-
47 For the past month, a 33-year-old woman has had phatase, 69 U/L; creatine kinase, 483 U/L; and creatinine, 1.3
burning epigastric pain and nausea and vomiting. An upper mg/dL. The presence of antibodies to which of the following
gastrointestinal endoscopic study shows multiple 1-cm shal- is most characteristic of his condition?
low gastric antral and proximal duodenal ulcerations. She is A ANCA
treated with omeprazole and improves. One year later, she B Cyclic citrullinated peptide
has an episode of severe, colicky lower abdominal pain and C Histone
hematuria and passes a calcium oxalate calculus. She notes ga- D Smith
lactorrhea 1 month later, and over the next 2 months ceases to E Thyroid peroxidase
F U1-RNP
50 A family pedigree reveals first- and second-generation
female relatives with premature menopause and male rela-
tives with a progressive neurodegenerative disorder start-
ing by their sixth decade. There are more males than females
exhibiting mental retardation from childhood by the fourth
generation. Genetic analysis of affected persons reveals CGG
repeat expansions in a gene encoding for a protein that binds
mRNA transcripts in neurons and shuttles them to the synapses.
An abnormality involving which of the following organs is
most likely to be present in affected males?
A Adrenal
B Pancreas
C Pituitary
D Testis
E Thyroid
4 7 4 U N I T I I Diseases of Organ Systems 80/min, respirations are 21/min, and blood pressure is 150/70
mm Hg. His spleen tip is palpable, and there is left upper quad-
51 A 44-year-old woman has noted dull right upper quad- rant tenderness. There is bilateral costovertebral angle tender-
rant pain for the past year. On physical examination, there is ness. A diastolic murmur is heard at the left sternal border.
right upper quadrant tenderness on palpation. Abdominal CT Subungual hemorrhages are noted on the digits of his hands.
scan shows a 5-cm circumscribed mass in the superior right A needle track is present in the left antecubital fossa. Labora-
lobe of the liver. The figure shows the representative gross ap- tory findings show WBC count, 12,700/mm3; glucose, 66 mg/dL;
pearance of a similar mass. She experiences acute chest pain AST, 101 U/L; and ALT, 28 U/L. Urinalysis shows 1+ hema-
with rapid dyspnea with diaphoresis 1 month later. Mul- turia, and WBCs and WBC casts. A chest radiograph shows a
tiple peripheral perfusion defects are seen on a pulmonary 3-cm nodule with an air-fluid level in the right upper lobe. What
ventilation-perfusion scan. Which of the following combina- organism is most likely to be cultured from his blood?
tions of p harmacologic agents taken by this patient regularly A Candida albicans
is most likely to be associated with these findings? B Cryptococcus neoformans
A Allopurinol and sulfamethoxazole C Escherichia coli
B Ethynyl estradiol and norethindrone D Listeria monocytogenes
C Ibuprofen and acetylsalicylic acid E Staphylococcus aureus
D Isoniazid and rifampicin F Streptococcus pyogenes
E Phenacetin and acetaminophen G Yersinia enterocolitica
52 A 37-year-old primigravida at 30 weeks’ gestation has
noted increasing pedal edema, headaches, confusion, and de- 54 A 41-year-old woman has had headaches with blurred vi-
creased urine output for the past 2 weeks. She now exhibits sion for the past 3 days and increasing mental confusion in the
seizure activity and then lapses into a coma. On physical ex- past day. On examination, her temperature is 37.9° C, pulse is
amination, her temperature is 36.8° C, pulse is 82/min, respi- 104/min, respirations are 25/min, and blood pressure is 70/40
rations are 24/min, and blood pressure is 145/95 mm Hg. Her mm Hg. She has petechial hemorrhages over her arms and
heart rate is regular, and lung fields are clear. The abdomen trunk. A stool sample is positive for occult blood. Laboratory
is soft, and bowel sounds are present. There is pitting edema findings show hemoglobin of 9.1 g/dL, hematocrit of 27.2%,
to the thighs. No vaginal bleeding is noted, and the cervix is MCV of 92 μm3, RDW of 19%, platelet count of 8900/mm3, and
not effaced. Laboratory findings show hemoglobin, 11.9 g/dL; WBC count of 8950/mm3. The peripheral blood smear shows
hematocrit, 35.8%; platelet count, 63,500/mm3; WBC count, schistocytes. A serum panel shows creatinine, 3.3 mg/dL; urea
8180/mm3; glucose, 151 mg/dL; total protein, 6.1 g/dL; albu- nitrogen, 32 mg/dL; and glucose, 80 mg/dL. Ultralarge mul-
min, 3.2 g/dL; total bilirubin, 2.3 mg/dL; AST, 88 U/L; ALT, timers of von Willebrand factor are present in plasma. What
103 U/L; alkaline phosphatase, 253 U/L; and prothrombin therapy should she receive emergently?
time, 32 seconds (INR 2.8). Urinalysis shows specific gravity A Two units of packed RBCs
of 1.024, pH 6, 4+ proteinuria, 1+ glucosuria, and no blood. An B Six-pack of platelets
ultrasound examination shows a viable 30-week fetus. What C Dobutamine
condition is most likely present in this patient? D Exploratory laparotomy
A Abruptio placentae E Plasmapheresis
B Budd-Chiari syndrome F Prednisone
C Dilated cardiomyopathy
D HELLP syndrome 55 A 30-year-old woman has noted a 5-kg weight gain over
E Hydatidiform mole the past 3 months; she has not had a menstrual period during
F Reye syndrome that time. She has experienced upper abdominal pain for the
G Sheehan syndrome past month. Physical examination shows abdominal enlarge-
53 A 29-year-old man has had increasing fatigue, a 2-kg ment with apparent ascites. There is no peripheral edema. She
weight loss, and a low-grade fever for the past 2 weeks. On has a positive pregnancy test. Additional laboratory findings
physical examination, his temperature is 37.5° C, pulse is show hemoglobin, 13.2 g/dL; hematocrit, 39.7%; WBC count,
12,300/mm3; glucose, 80 mg/dL; AST, 581 U/L; ALT, 611 U/L;
total bilirubin, 1.3 mg/dL; total protein, 6.2 g/dL; and albu-
min, 3.5 g/dL. Because she has family history of pulmonary
embolism, she is tested for and found to have Factor V Leiden
mutation. An abdominal ultrasound scan shows hepatomegaly
with heterogeneous echogenicity, and there is an intrauterine
gestation with a fetus estimated at 12 weeks’ size. What patho-
logic finding is most likely to be present in her liver?
A Choledocholithiasis
B Chronic passive congestion
C Hepatic venous thrombosis
D Hepatocellular adenoma
E Metastatic choriocarcinoma
F Microvesicular steatosis
56 A 26-year-old woman has had increasingly frequent C H A P T E R 3 0 Final Review and Assessment 4 7 5
infections over the past 5 years. Her most recent respiratory 59 A 22-year-old woman has sudden onset of severe lower
infection was due to Streptococcus pneumoniae. She now has abdominal pain. Her medical history includes Chlamydia tra-
watery diarrhea. On physical examination, she is below ideal chomatis cervicitis. On physical examination, her temperature
weight. There is a vesicular rash in the T10 dermatomal dis- is 36.9° C, pulse is 90/min, respirations are 17/min, and blood
tribution on the left. Laboratory findings include WBC count, pressure is 90/50 mm Hg. There is lower abdominal tender-
7200/mm3 with 55% segmented neutrophils, 2% bands, 35% ness, but no palpable masses. No vaginal bleeding is present.
lymphocytes, 6% monocytes, and 2% eosinophils. Quantita- The rectal examination is unremarkable, and a stool sample is
tive immunoglobulins include IgA of 22 mg/dL, IgG of 175 negative for occult blood. Bowel sounds are reduced. An ab-
mg/dL, and IgM of 40 mg/dL. Lymphocyte subsets by flow dominal ultrasound scan is performed, and the uterus appears
cytometry show CD4+ cells (absolute) of 630/μL, CD8+ cells normal in size with no masses visualized, but there is a right
(absolute) of 785/μL, B cells of 280/μL, and T cells of 2010/μL. adnexal mass. Culdocentesis is performed, and there is blood
A stool sample examined for ova and parasites shows Giardia in the aspirate. Laboratory findings show hemoglobin of 9.5
lamblia cysts. What is the most likely immunodeficiency disor- g/dL, hematocrit of 28.6%, platelet count of 269,300/mm3, and
der in this woman? WBC count of 9110/mm3. Which of the following laboratory
A Chronic granulomatous disease findings is most likely to be present in this woman?
B Common variable immunodeficiency A Decreased coagulation factor XIII
C Hyper-IgM syndrome B Decreased follicle-stimulating hormone
D Leukocyte adhesion deficiency C Increased carcinoembryonic antigen
E Severe combined immunodeficiency D Increased human chorionic gonadotropin
E Entamoeba histolytica cysts in stool
57 A 44-year-old man has had worsening exercise toler- F Schistosoma haematobium eggs in urine
ance and peripheral edema during the past 5 years. He has
noted increasing central opacifications that interfere with
vision. He has frontal baldness. During the past 2 years, he 60 A 43-year-old woman has become increasingly tired and
has had progressive memory loss with decreasing ability to listless over the past 5 months. She has had menometrorrha-
perform activities of daily living. On physical examination, gia for the past 3 months. On physical examination, there are
there is significant atrophy of masseter, temporalis, scalene, no remarkable findings except for a positive result on stool
deltoid, trapezius, and sternocleidomastoid muscles. There guaiac testing. Laboratory studies show hemoglobin, 9.2 g/
is bilateral testicular atrophy. A 2-hour glucose tolerance test dL; hematocrit, 27.3%; and MCV, 75 μm3. Pelvic ultrasound
shows serum glucose of 156 mg/dL. There is hypogamma- reveals an enlarged uterus. A Pap smear shows abnormal cells
globulinemia. His condition worsens over the next 3 years, of probable endometrial origin. Colonoscopy is performed,
with increasing muscular weakness. An abnormality in which followed by partial colectomy; the gross appearance of the le-
of the following gene products is most likely to be present in sion is shown in the figure. Which of the following molecular
this man? abnormalities has most likely led to these findings?
A α-1,4-Glucosidase A Germline inheritance of APC gene mutation
B Dystrophin B Homozygous loss of PTEN gene
C Fibroblast growth factor receptor 3 C Inactivation of the Rb protein by HPV-16
D Mitochondrial oxidative phosphorylase D Mutation in a DNA mismatch-repair gene
E Myophosphorylase E Tyrosine kinase activation caused by c-KIT
F Myotonic dystrophy protein kinase
mutation
58 A 53-year-old man is found comatose on the floor of his
bathroom. His neighbors say there was a party at his residence
and they saw many acutely intoxicated people staggering out-
side. Vital signs on arrival in the emergency department are
temperature, 36° C; pulse, 88/min; respirations, 16/min; and
blood pressure, 95/60 mm Hg. There are no signs of trauma.
Laboratory studies show blood ethanol level of 0.20 gm%.
Which of the following substances found in his urine are most
likely to cause acute kidney injury?
A Cystine crystals
B Glucose
C Hyaline casts
D Ketones
E Myoglobin
4 7 6 U N I T I I Diseases of Organ Systems 63 A 29-year-old man notes burning pain on urination with
a urethral discharge that has persisted for 3 days. A sample
61 A 51-year-old man living on the island of St. Helena has of the exudate is positive by ELISA for Chlamydia trachomatis.
had a downturn in his political fortunes. Over the past 3 years, The man has increasing stiffness of the knees and ankles and
and particularly over the past year, he has had increasing lower back pain 3 weeks later. A radiograph of the lumbar
bouts of abdominal pain, anorexia, nausea, vomiting, dysuria, spine shows narrowing with sclerosis of the sacroiliac joints.
lethargy, spiking fevers, diarrhea, constipation, excessive One month later, he develops painful erythema of the glans
weakness, heavy perspiration, and weight loss. He is given penis, and the conjunctivae are red. A follow-up examination
a large dose of calomel (a mercury-containing compound) a shows a slightly irregular heart rate and a murmur sugges-
few days before his death on May 5, 1821, a treatment that tive of aortic regurgitation. The back pain continues off and on
has since vanished for good reason. An autopsy shows hepa- for 5 more months. Which of the following test results is most
tomegaly (with steatosis?) and ulceration with thickening of likely to be positive in this man?
the stomach. The autopsy report does not record skin and nail A ANCA
changes, such as hyperkeratosis and hyperpigmentation. If B ANA
those changes had been present, and squamous cell carcinoma C HLA-B27 genotype
of the skin, the findings would have been most suggestive of D Anti-Borrelia antibodies
chronic poisoning with which of the following metals? E Rapid plasma reagin
A Arsenic F Rheumatoid factor
B Beryllium G U1-RNP
C Chromium
D Cobalt
E Lead
F Nickel
62 A 90-year-old woman died suddenly. Autopsy shows a 64 A 19-year-old man has been having headaches for the
5-cm skin ulceration extending to the sacrum. She had diffuse past month. On physical examination, his blood pressure is
muscle wasting; a microscopic section shows decreased size 160/95 mm Hg. On funduscopic examination, there are bila
of muscle fibers without inflammation or fibrosis. Her bones teral retinal angiomas. Abdominal CT scan shows a 3-cm mass
show marked osteoporosis, and there is vertebral column involving the right adrenal gland. Laboratory testing shows
kyphosis. A finding on examination of the lungs is shown in increased urinary catecholamines. The mass is removed surgi-
the figure. There is pneumonia in the lower lobe of the right cally. He develops a movement disorder 5 years later with in-
lung. Which of the following conditions most likely predis- coordination and ataxia. MRI of the brain shows a 2-cm mass
posed this patient to the pathologic findings seen at autopsy? in the left cerebellar hemisphere and a 1-cm mass in the vermis.
A Antiphospholipid syndrome These are removed surgically. Six years later, he has right
B Aplastic anemia flank pain with hematuria; his abdominal CT scan is shown
C Chronic alcoholism in the figure. His hemoglobin concentration is 20.3 g/dL, and
D Elder abuse with blunt trauma hematocrit is 60.9%. Which of the following gene mutations
E Immobilization and associated syndrome does he most likely have?
F Malnutrition A APC—Gardner syndrome
B MET—Denys-Drash syndrome
C NF2—Neurofibromatosis type 2
D TSC1—Tuberous sclerosis
E VHL—Von Hippel–Lindau disease
F WT1—Beckwith-Wiedemann syndrome
65 A 43-year-old woman has had increasing difficulty swal- C H A P T E R 3 0 Final Review and Assessment 4 7 7
lowing over the past year. She notices that her hands turn white
and are painful on exposure to cold. She remarks, “I may be petechiae on his arms and legs. His heart rate is regular and
getting older, but at least I don’t have any wrinkles on my face the lungs are clear. No neurologic deficits are noted. Labora-
or hands yet.” On physical examination, her blood pressure is tory findings show hemoglobin, 11.1 g/dL; hematocrit, 33.1%;
115/75 mm Hg. The skin of her face and hands appears taut and MCV, 72 μm3; platelet count, 317,200/mm3; and WBC count,
shiny. A punch biopsy specimen of the skin of the hand shows 5915/mm3. The partial thromboplastin time and the prothrom-
dermal collagenous fibrosis and focal calcification. She receives bin time are normal. Platelet function analysis shows decreased
yearly esophageal dilation for the next 20 years, during which aggregation in response to ADP and collagen stimulation. An
time she develops no serious illnesses. Which of the following upper gastrointestinal endoscopy shows gastric mucosal ery-
serologic test results is most likely to be positive in this woman? thema and a 1.8-cm, sharply demarcated, shallow, antral ulcer-
A Anticentromere antibody ation. Long-term use of which of the following pharmacologic
B Anti–DNA topoisomerase antibody agents is most likely to produce these findings?
C Antimicrosomal antibody A Acetylsalicylic acid
D Antimitochondrial antibody B Acetaminophen
E Anti–neutrophil cytoplasmic autoantibody C Adalimumab
F Antitransglutaminase antibody D Methotrexate
E Oxycodone
F Propoxyphene
66 A 32-year-old woman has had increasing malaise and a
10-kg weight loss over the past 6 months. Physical examination 68 A 16-year-old girl has had irregular menstrual cycles
shows muscle wasting, and there is a tan-yellow, plaquelike since menarche 2 years ago and has not menstruated for 3
coating on her tongue. A scraping of the material from her months. She has not used contraceptives. One week ago, she
tongue microscopically shows budding cells with pseudo- noticed a small amount of vaginal bleeding and now has sud-
hyphae. She develops watery diarrhea 6 months later; a stool den onset of severe abdominal pain. On physical examination,
specimen contains cysts of Cryptosporidium parvum. She then there is marked right upper quadrant abdominal tenderness,
develops a fever, cough, and severe dyspnea. Bronchoalveolar and bowel sounds are reduced. A stool sample is negative for
lavage is done; the figure shows the microscopic findings with occult blood. Brownish fluid is noted emanating from a red-
GMS staining. Which of the following laboratory findings is dish brown, 2-cm mass in the vaginal vault. Her serum hCG
most likely to be present in this woman? level is high. An abdominal ultrasound examination shows
A ANA titer of 1:1024 multiple 3- to 6-cm masses in the liver, and the uterus appears
B CD4+ lymphocyte count of 111/μL enlarged. A chest radiograph shows 1- to 3-cm nodules in the
C Complement C2 undetectable lungs. Paracentesis is done, and there is blood in the aspirate.
D IgG of 88 mg/dL What neoplasm would most likely produce these findings?
E Neutrophil oxidative burst assay less than 5% A Adenocarcinoma
F Positive rapid plasma reagin B Choriocarcinoma
67 A 73-year-old man has had bilateral knee and hip pain C Clear cell carcinoma
for the past 25 years and has taken a medication for this pain D Leiomyosarcoma
for the past 5 years. During the past year, he has noticed in- E Malignant mixed müllerian tumor
creasing frequency of headaches, dizziness, tinnitus, confu- F Sarcoma botryoides
sion, and nausea. One week ago, he experienced an episode
of hematemesis. On physical examination, there are scattered 69 A 44-year-old woman has had easy fatigability along
with pain and stiffness of both wrist joints and other small
joints of the hands for the past 8 years. The stiffness is marked
in the morning and abates as the day goes by. Radiographs of
her hands reveal narrowing of the proximal interphalangeal
and metacarpophalangeal joint spaces from synovitis and ero-
sion of the cartilage. Laboratory tests show Hgb, 8.4 g/dL; Hct,
23.5%; MCV, 65 fL; and MCH, 23 pg. Her peripheral blood
smear shows hypochromic, microcytic RBCs. Her serum iron
and iron binding capacity levels are low and the ferritin level
elevated. A high level of which of the following is most likely
related to the causation of anemia in this woman?
A C-reactive protein
B GM-CSF
C Hepcidin
D Rheumatoid factor
E TNF
4 7 8 U N I T I I Diseases of Organ Systems
70 A study of children with bone deformities assesses risk 73 A 5-year-old child who has received no medical care
factors for their disease. One cohort of these children is found since birth has had gradual onset of markedly decreased vision
to have bone with the microscopic appearance shown in the bilaterally. The child also has a history of increased respiratory
figure panel at the left, compared to that of bone in normal tract infections caused by Haemophilus influenzae, Streptococ-
children, shown in the panel at the right. Symmetric deformi- cus pneumoniae, Klebsiella pneumoniae, and rubeola. The figure
ties include frontal bossing, long bone bowing, pronounced shows the representative microscopic appearance of the bron-
lumbar lordosis, and costochondral junction widening. No chial mucosa. The child also has passed urinary tract calculi.
skin or soft tissue abnormalities are noted. What is the most On physical examination, generalized papular dermatosis is
likely underlying risk for this spectrum of bone deformities? noted. The child has xerophthalmia, and there is marked kera-
A Dietary deficiency of fresh fruit tomalacia with corneal clouding. Bilateral crackles are audible
B Diminished sunlight exposure in the lungs on auscultation. Which of the following diseases
C Hypopituitarism would most likely lead to these findings?
D Inherited mutation in vitamin D receptor A Cystic fibrosis
E Trauma from child abuse B Congenital syphilis
C HIV infection
71 A 4-month-old boy was born at term to an 18-year-old D Kartagener syndrome
woman, G1, P0, after a normal pregnancy. The woman r eturned E Vitamin A deficiency
home from work one evening and was told by her boyfriend,
who is staying at her home, that the infant died suddenly. An 74 A 47-year-old woman has had increasing abdominal en-
autopsy shows no external anomalies. The infant’s height and largement, with no significant pain, and diarrhea for the past 3
weight are at the 45th percentile. Internal examination reveals months. There is a fluid wave on examination of the abdomen.
subarachnoid hemorrhage at the vertex and subdural hemor- Abdominal CT scan shows massive ascites and scattered 0.5- to
rhage over the right parietal lobe. The right eye shows petechial 1.5-cm cystic to solid nodules on the surfaces of the bowel and
hemorrhages at the ora serrata. There is a soft-tissue hemorrhage abdominal wall. Paracentesis yields a yellow, slightly cloudy
in the right upper arm. There is a recent fracture of the occipital fluid with a high protein content. Cytologic examination of
bone. What is the most likely diagnosis? the fluid shows clusters of malignant cells. Laboratory stud-
A Congenital syphilis ies show a positive CA 125, no elevation of HCG level, and a
B Hemophilia A negative carcinoembryonic antigen test result. What is the most
C Osteogenesis imperfecta likely neoplasm?
D Child abuse injuries A Adenocarcinoma of the ileum
E Sudden infant death syndrome B Carcinoid tumor
F Thanatophoric dysplasia C Choriocarcinoma
D Malignant mesothelioma
72 A 35-year-old man presents with increasing breathless- E Serous cystadenocarcinoma
ness on exertion. On physical examination, his height is 208 F Mucinous cystadenoma
cm (82 inches) with long arms and tapering fingers. His joints
are exceptionally flexible. He also has bilateral subluxation of 75 What is the ultimate answer in health care, as in life?
crystalline lenses. Echocardiography reveals mitral valve pro- A A sound diet with exercise prevails
lapse and an aneurysm in his ascending aorta. Which of the B Diagnose early and treat appropriately
following experimental therapies is likely to be beneficial in C Environmental controls aid prevention
treating this man? D Love is the healer for all our ills
A Anti–TGF-β antibody E Research and develop new therapies
B Bone marrow transplantation
C Low-calorie, low-cholesterol diet
D Lysosomal stabilizing agents
E Transduction of fibrillin-1 gene into T cells
C H A P T E R 3 0 Final Review and Assessment 479
A Collegial consultation
76 As a student in the health sciences, you have just fin- B Compassionate care
ished this review book, learning to apply your knowledge C Differential diagnosis
base in pathology to clinical and experimental scenarios of D Lifelong learning
human disease states. Which of the following represents your E Patient education
best application of this knowledge? F Research projects
ANSWERS and finely granular surface that looks like sandpaper. Extra
intestinal manifestations of ulcerative colitis can occur, includ-
1 E Acute myocardial infarction, cerebrovascular disease, ing primary sclerosing cholangitis (PSC), uveitis, migratory
and peripheral vascular disease at a young age suggest het- polyarthritis, and erythema nodosum. Sixty percent to 70%
erozygous familial hypercholesterolemia with a mutation in of cases of PSC have concurrent inflammatory bowel dis-
the gene encoding for the LDL receptor. Such individuals ease. Atrophic gastritis causes pernicious anemia and may
have early, accelerated atherosclerosis. The statin drugs are coexist with other autoimmune disorders, such as Hashimoto
HMG-CoA reductase inhibitors that suppress endogenous thyroiditis. Dermatitis herpetiformis occurs in patients with
cholesterol synthesis and increase LDL receptor synthesis. celiac disease, both caused by gluten sensitivity. Orchitis is
Acetylcholine receptors at the neuromuscular junction may most often a complication of mumps virus infection, partic-
be targeted by antibodies in myasthenia gravis. The patient ularly in adults. Rheumatoid arthritis is typically associated
does not have findings consistent with diabetes mellitus, with Sjögren syndrome. Thyroiditis may occur in association
another disease that promotes atherosclerosis, because his with other autoimmune endocrinopathies, such as Addison
hemoglobin A1c level is normal, indicating that hyperglyce- disease.
mia has not been present. In type 1 diabetes mellitus, there
is reduced beta cell mass; in type 2 diabetes mellitus, there PBD9 800–802, 859–860 BP9 591–592, 628 PBD8 811–812
can be a reduction in glucose transport, but insulin receptors BP8 614–616
are generally not involved. Hepcidin is involved in control of
iron absorption. 4 E Toxic shock syndrome can be caused by some strains
of Staphylococcus aureus that produce exotoxins acting as
PBD9 147, 495 BP9 222, 336 PBD8 497 BP8 232–233 superantigens, such as TSST-1, which are T-cell mitogens.
These superantigens are able to stimulate more than 10% of
2 C Atopic bronchial asthma usually begins in childhood. the body’s T cells, provoking an exuberant and dysregulated
Although many of the symptoms of bronchial asthma can be immune response characterized by release of the cytokines
related to type I hypersensitivity, this disease is fundamen- that mediate cell injury. Bacillus anthracis can cause anthrax,
tally T cell–mediated chronic inflammation of the bronchial a serious illness with pneumonia and meningitis as the pre-
wall. The TH2 type CD4+ T cells drive type I hypersensitiv- dominant findings. Clostridium perfringens is known to cause
ity by favoring IgE production and eosinophil recruitment. wound infections with gas gangrene. Enterococcus generally
The dominance of TH2 helper cells is accompanied by down- does not cause such a rapidly progressing illness. Listeriosis is
regulation of the TH1 helper cells because the CD4+ T-cell associated with food poisoning and can cause life-threatening
differentiation is skewed toward TH2 cells. Neutrophils, disease, but typically without desquamation. Vibrio vulnificus
eosinophils, and macrophages also can be present in the in- organisms may cause a blistering dermatitis, but this infection
flammatory exudates, but these cells all are recruited second- follows ingestion of contaminated shellfish.
arily to the TH2 response. ADAM-33, a metalloproteinase,
has been linked to the airway remodeling seen in bronchial PBD9 363 BP9 321 PBD8 357 BP8 334
asthma. Specifically, certain polymorphisms of the ADAM-
33 gene are associated with proliferation of bronchial smooth 5 B Features of acute cocaine toxicity, such as hyperther-
muscle cells and fibroblasts. There is, however, no evidence mia, and chronic cocaine use, with coronary arteriopathy
that ADAM-33 contributes to the immunologic alterations and cerebral hemorrhagic strokes, are present. The brown
seen in bronchial asthma. discoloration from hemosiderin deposition in the left ante-
rior frontal lobe suggests a subacute to remote hemorrhage.
PBD9 679–683 BP9 468–470 PBD8 688–692 BP8 489–492 Cocaine is a powerful vasoconstrictor. Similar to cocaine, am-
phetamine and methamphetamine are uppers, or stimulants;
3 D Ulcerative colitis has a peak age of onset between 15 however, they do not typically produce arterial changes.
and 30 years. A second peak occurs between 60 and 80 years.
The colonoscopic appearance is of a mucosal erythematous
4 8 0 U N I T I I Diseases of Organ Systems
Barbiturates are downers, or depressants. Ethanol is a de- and hemolysis. An elevated amylase level could be seen in
pressant that can produce liver disease, but the cardiac effect acute pancreatitis, which could occur with gallstones, but
is obscure and results in dilated cardiomyopathy after years this would not explain the anemia or the undetectable spleen.
of abuse. Heroin is an opiate narcotic that has minimal effects Antiphospholipid syndrome (APS) with anticardiolipin anti-
itself, but the typical route of administration is intravenous, bodies leads to thrombosis, but the abdomen is not the typical
and this can lead to numerous infectious complications, such location, and the anemia is not explained by APS. Pancreatitis
as hepatitis, endocarditis, meningitis, and AIDS. Marijuana is can complicate hypercalcemia and hypertriglyceridemia, but
a mild tranquilizer. Phencyclidine is a schizophrenomimetic this does not explain the anemia or undetectable spleen. An
that causes erratic behavior, but not obvious tissue effects. increased cholesterol is a risk for atherosclerotic diseases.
PBD9 423–424 BP9 284–285 PBD8 417–418 BP8 295–296 PBD9 635–638 BP9 411–413 PBD8 645–648 BP8 426–428
6 D Morbid obesity can be associated with complications 9 B Hemoglobin A1c elevation occurs in diabetes melli-
that include obesity hypoventilation syndrome, probable tus. The patient has complications of type 2 diabetes melli-
sleep apnea, glucose intolerance, cholelithiasis, and osteoar- tus that are typical of obesity: a “diabetic foot” as a conse-
thritis. Macrovesicular steatosis with hepatomegaly is seen quence of peripheral neuropathy and decreased sensation,
in obesity and may even progress to cirrhosis. Weight gain advanced atherosclerosis with carotid arterial occlusion, and
owing to h ypothyroidism, which could occur in Hashimoto an atherosclerotic aortic aneurysm. Autonomic dysfunction
thyroiditis, is modest and does not lead to morbid obesity. with neuropathy can lead to erectile dysfunction. The oligo-
An “obesity cardiomyopathy” resembles dilated cardio- clonal bands of IgG are characteristic for multiple sclerosis,
myopathy, but not hypertrophic cardiomyopathy, which which usually has more focal CNS involvement. Cushing
typically involves the interventricular septum with myofiber disease owing to an ACTH-secreting pituitary adenoma
disarray. Laryngeal papillomatosis, which produces airway leads to truncal obesity, skin that is easily bruised, and pos-
obstruction (without snoring), occurs more often in children sibly to secondary diabetes mellitus, but not to advanced
and is not associated with obesity. The blood gas findings in a therosclerosis. Hyperchromocysteinemia is a risk factor for
this case could be seen in emphysema, which is not a com- atherosclerosis, but not for neuropathy. Anti–parietal cell
plication of obesity; panlobular emphysema is much less antibodies occur in pernicious anemia with vitamin B12 de-
common than the centrilobular emphysema associated with ficiency, which can lead to decreased sensation in the lower
smoking. Rheumatoid arthritis tends to involve small joints extremities, but not to atherosclerotic complications.
first, and there is no relationship to obesity.
PBD9 1113–1120 BP9 743–749 PBD8 1143–1146 BP8 775–783
PBD9 444–448 BP9 302–304 PBD8 442–443 BP8 313–317
1 0 D The acute neuronopathic form of Gaucher disease
7 F Tertiary syphilis may manifest with syphilitic aortitis (type 2) is uniformly fatal in children and thankfully is much
from endarteritis obliterans of the vasa vasorum, which is less common than the milder type 1, which has prolonged
most marked in the proximal aorta. In addition, the patient survival into adulthood. The marrow is infiltrated by large
has findings of neurosyphilis, with tabes dorsalis and general cells with abundant pale cytoplasm with the appearance of
paresis. A positive VDRL test result on CSF aids in diagnosis. crumpled tissue paper. α-l-Iduronidase deficiency is seen
None of the remaining organisms listed produces aortic dis- in Hurler syndrome, characterized by progressive features
ease. Neuroborreliosis from Lyme disease can produce aseptic of corneal clouding, coarse facial features, and mental re-
meningitis, encephalopathy, and polyneuropathy. Coxsacki- tardation. α-1,4-Glucosidase deficiency is present in Pompe
evirus B can produce meningoencephalitis and myocarditis. disease, a glycogen storage disease that causes marked car-
HIV can produce encephalitis characterized by dementia diomegaly. Arylsulfatase A deficiency is present in meta-
and motor and sensory deficits. Hansen disease, caused by chromatic leukodystrophy and causes CNS degeneration
Mycobacterium leprae infection, mainly affects the peripheral without visceral organ involvement. Tay-Sachs disease with
nerves. Tuberculosis can produce meningoencephalitis or a cherry-red maculae and progressive neurologic deterioration
mass known as a tuberculoma; obstructive hydrocephalus may occurs as a result of diminished hexosaminidase A. Sphin-
occur in chronic meningitis. West Nile virus is most likely to gomyelinase deficiency leads to Niemann-Pick disease, with
produce severe meningoencephalitis in elderly individuals. foamy-appearing macrophages filling tissues of the mono-
nuclear phagocyte system.
PBD9 378–381, 1274–1275 BP9 346, 826 PBD8 508, 1301–1302
BP8 359, 875 PBD9 153–154 BP9 231–232 PBD8 153–154 BP8 237–238
8 E Sickle cell anemia (hemoglobin SS) may present with 1 1 D Pernicious anemia can be due to atrophic gastritis,
abdominal crisis and vertebral bone marrow infarction. The with lack of intrinsic factor to bind dietary vitamin B12 for ab-
haptoglobin is low as a result of sickle cell crisis with hemo- sorption. This condition has led to megaloblastic anemia and
lysis. The continued hemolysis leads to formation of pig- subacute combined spinal cord degeneration. The anti-Smith
mented gallstones. Autosplenectomy is a consistent finding. antibody is a feature of systemic lupus erythematosus, which
There is a predisposition to aseptic necrosis and osteomyeli- has many manifestations, but not typically gastritis or spinal
tis, particularly with Salmonella. The MCV is high because of cord degeneration. Factor V (Leiden) deficiency is a risk factor
reticulocytosis, and the RDW is quite high because of sickling for recurrent thrombosis. Helicobacter pylori infection leads to
C H A P T E R 3 0 Final Review and Assessment 4 8 1
gastritis (not typically atrophic), but not to neurologic prob- should have been identified, as would pelvic inflammatory
lems. An elevated urine glucose level suggests diabetes mel- disease that may produce a tubo-ovarian abscess.
litus, which may lead to peripheral neuropathy, but not to
gastritis. PBD9 624 BP9 456 BPD8 633 BP8 475
PBD9 647–648, 765 BP9 423, 567 PBD8 778–779 BP8 438–439, 592 15 A The chest CT scan shows a thymoma posterior to the
sternum just below the clavicles. The findings listed describe
12 D The C282Y mutation in the HFE gene can be found myasthenia gravis with complications of thymoma, includ-
in one in nine individuals of Celtic heritage and causes in- ing the rare finding of pure RBC aplasia, which is charac-
creased absorption of dietary iron. In men beginning around terized by selective suppression of the erythroid lineage
age 40 years, the increased iron stores lead to organ dysfunc- in the bone marrow. In about half of such cases, removal
tion, typically involving the heart (cardiomyopathy with of the thymic tumor relieves the RBC aplasia, suggesting
congestive heart failure), pancreas (diabetes mellitus), skin some autoimmune mechanism as the cause of the aplasia.
(increased pigmentation), and joints (arthritis). In women, Thymic disorders are common in myasthenia gravis, either
increased iron loss through menses delays the onset of this thymic hyperplasia or thymoma (as in this case). Antibod-
disease for 20 more years. A patient with β-thalassemia ies against the acetylcholine receptor disrupt the function of
would have anemia, although the ineffective erythropoiesis the myoneural junction. Anti–DNA topoisomerase is seen in
leads to excessive iron absorption. Although this patient scleroderma, in which there is renal failure and skin thick-
has diabetes mellitus and an increased glucose level, dia- ening, but not muscle weakness after use. Anti–glomerular
betes mellitus does not explain all the findings, such as the basement membrane antibody can be seen in Goodpasture
arthritis. Familial hypercholesterolemia could lead to coro- syndrome, a form of rapidly progressive glomerulonephri-
nary artery disease and heart failure, but it does not explain tis, often with pulmonary hemorrhage. Antimitochondrial
the patient’s diabetes or arthritis. Rheumatoid arthritis with antibody may be seen in primary biliary cirrhosis. ANA is
joint inflammation mediated in part by TNF typically leads characteristic of many systemic autoimmune diseases, most
to joint deformities and mostly involves small joints. often systemic lupus erythematosus, which can be accompa-
nied by myalgias, but not by muscle weakness with repeti-
PBD9 847–849 BP9 629–630 PBD8 861–863 BP8 654–656 tive movement.
13 F Systemic lupus erythematosus (SLE) manifestations PBD9 206, 627, 655 BP9 115, 457 PBD8 636–637 BP8 476, 830
may include photosensitivity, renal failure, body cavity ef-
fusions, pericarditis, arthralgias, myalgias, and cytopenias. 1 6 A Goodpasture syndrome has antibody directed
The antinuclear antibody test is the most sensitive screening against the glomerular basement membrane, which also acts
test for SLE, and if positive can be followed by the more spe- on basement membrane in the lung to produce pulmonary
cific anti–double-stranded DNA antibody test. Acetylcholine hemorrhage and hemoptysis. Cytotoxic CD8+ lymphocytes
receptor antibody may be seen in myasthenia gravis, which are part of a cell-mediated immune response effective in
would explain muscle weakness but not pain. Anti–DNA eliminating intracellular infections such as influenza. Circu-
topoisomerase is seen in scleroderma, in which there is re- lating immune complexes are more likely to be seen in au-
nal failure and skin thickening, but not photosensitivity. toimmune diseases, such as systemic lupus erythematosus.
Anti–glomerular basement membrane antibody can be seen Macrophage activation is more typical of chronic inflamma-
in Goodpasture syndrome and renal failure, but not arthral- tion and granulomatous inflammation with type IV hyper-
gias, myalgias, or cytopenias. Antimicrosomal (anti–thyroid sensitivity. Release of mediators such as histamine from mast
peroxidase) antibody is associated with autoimmune thyroid cells is typical of anaphylaxis with type I hypersensitivity.
diseases, mainly Hashimoto thyroiditis, but also Graves dis-
ease. Antimitochondrial antibody may be seen in primary PBD9 701, 912–913 BP9 485, 532 PBD8 709–710, 920
biliary cirrhosis, which leads to malaise, but not to renal fail- BP8 124, 507–508, 557–558
ure or photosensitivity.
17 F The ascites, edema, and splenomegaly together with
PBD9 218–226 BP9 125–131 PBD8 213–221 BP8 139–144 laboratory evidence of hepatic dysfunction suggest a hepatic
disorder with portal hypertension, and a common cause is
14 A She has fever of unknown origin (FUO), at least until hepatic cirrhosis from chronic alcohol abuse. Decreased es-
a record review correlated with the CT imaging suggests that trogen metabolism results in testicular atrophy. The findings
the mass is a residual hemostatic sponge placed at the time of right-sided and left-sided congestive heart failure are as-
of surgery. Radiopaque markers or radio-frequency identi- sociated with alcoholic dilated cardiomyopathy. Macrocytic
fication (RFID) chips can be incorporated into such objects anemia is common, and the AST is slightly higher than the
for identification. The mild splenomegaly is consistent with ALT, features typical of chronic alcoholism. Addison disease
intra-abdominal abscess. There is a long differential diag- resulting from adrenal atrophy would not produce hypoal-
nosis list for FUO. A mass could represent a neoplasm, but buminemia or liver enzyme elevations, and the glucose level
lymphomas do not tend to have significant necrosis and a is often lower. Aortic stenosis may explain the pulmonary
lucent center. Sarcoidosis tends to involve multiple organs, edema. Autoimmune gastritis may lead to gastric mucosal
but lymph node enlargement is likely, although central ca- atrophy, loss of parietal cells, and megaloblastic anemia, but
seation is not. At the prior surgery, an ovarian neoplasm not to hepatic abnormalities. In chronic glomerulonephritis
4 8 2 U N I T I I Diseases of Organ Systems
severe enough to produce a hepatorenal syndrome, the renal associated with the appearance of various neoplasms, in-
failure would be much worse and would be indicated by a cluding neurofibromas, pheochromocytomas, and gliomas.
high serum creatinine. Dilated cardiomyopathy is a type of p53 is a tumor suppressor gene, and loss of both alleles can
cardiomyopathy typical of chronic alcoholism. promote the appearance of various malignancies, mainly
carcinomas.
PBD9 827–830, 842–845 BP9 608–610, 623–624 PBD8 837–839
BP8 290–292, 648–652 PBD9 466–471 BP9 223–227 PBD8 465–471 BP8 264–267
18 C Elusive as the yeti, the paradoxical embolism ex- 2 1 D Lead poisoning is mainly manifested by neurologic
plains her findings. She has thrombophlebitis with pulmo- disorders, particularly in children. Lead absorption is en-
nary embolism as a result of prolonged bed rest. Her chronic hanced by zinc deficiency; zinc is a trace metal. Lead inhibits
obstructive pulmonary disease has led to cor pulmonale with heme incorporation into hemoglobin, leading to increased
an enlarged right side of the heart, reversing the shunt across amounts of zinc protoporphyrin with anemia. Cadmium is
a ventricular septal defect. Shunt reversal allows a thrombo- a heavy metal associated with toxicity to the gastrointestinal
embolus arising in the venous circulation to reach the sys- tract, kidneys, and lungs. Copper is a trace metal that is un-
temic arterial circulation in the brain. A constrictive pericar- likely to cause toxicity from environmental sources, although
ditis yields a paradoxical pulse from impaired cardiac filling copper accumulation can occur with Wilson disease. Acute
and greater than normal decline in systolic arterial pressure iron poisoning is associated with gastrointestinal, renal, and
on inspiration; this is not associated with thromboembolism. CNS toxicities. Nickel jewelry may cause skin rash; inhaled
A dilated cardiomyopathy should lead to global cardiac en- nickel produces respiratory problems.
largement, not just enlargement of the right side of the heart,
and although mural thrombosis with embolism can occur, PBD9 410–412 BP9 274–275 PBD8 406–407 BP8 283–285
there is usually no association with thrombophlebitis. Infec-
tive endocarditis can lead to embolization, but in her case 2 2 E Granulomatosis with polyangiitis (ANCA-associated
there is no fever or infection. Rheumatic heart disease can vasculitis) is a multisystem vasculitis that most often involves
affect one or more valves, and often leads to left atrial en- the lungs and kidneys. C-ANCA is positive in 95% of patients.
largement with mural thrombosis and embolism, but the left Anti–DNA topoisomerase I antibody can be seen in diffuse
atrial border would be prominent, and the pulmonic valve is scleroderma, which produces pulmonary interstitial fibrosis
almost never involved. and renal hyperplastic arteriolosclerosis. Anti–glomerular
basement membrane antibody is seen in Goodpasture syn-
PBD9 533–535 BP9 371–372 PBD8 540 BP8 383–384 drome, which produces crescentic glomerulonephritis and
pulmonary hemorrhage, but not necrotizing vasculitis.
19 F Type 1 diabetes mellitus with ketoacidosis is the Anti–Jo-1 antibody accompanies polymyositis/dermato-
setting for infection by Mucor in the paranasal sinuses, an myositis. Antimitochondrial antibody accompanies primary
o therwise unusual infection. T-cell and B-cell function is gen- biliary cirrhosis. Anti-dsDNA is positive principally seen in
erally maintained in diabetes mellitus, although neutrophilic systemic lupus erythematosus (SLE), which can produce a
function may be depressed, so bacterial infections (staphy- vasculitis, but not a necrotizing granulomatous vasculitis.
lococcal, streptococcal, and coliform organisms) most often Anti-RNP antibody is positive in cases of mixed connective
complicate diabetes mellitus. Actinomycosis can produce tissue disease, which overlaps SLE, scleroderma, rheumatoid
chronic subcutaneous abscesses, usually in the neck, lung, arthritis, and polymyositis, but it usually does not entail
or abdomen, and usually following trauma or tissue devital- significant renal or pulmonary involvement.
ization. Cutaneous anthrax is rare and produces a localized
eschar or ulcerated region. Cytomegalovirus and cryptococ- PBD9 506–507, 701–702 BP9 349–350, 485 PBD8 516–517
cal infections are typically seen in immunocompromised in- BP8 367–368, 508, 558
dividuals with diminished cell-mediated immunity. Clostrid-
ium perfringens appears in the setting of soft-tissue infections 23 A Reactive systemic amyloidosis has developed from
with gas gangrene. her underlying granulomatous ileitis, and serum amyloid-
associated protein is generated by chronic inflammation.
PBD9 736, 1109–1110, 1279 BP9 741, 829 PBD8 385–386 Atrial natriuretic peptide can be seen with isolated atrial
BP8 527–528, 775–781 amyloidosis. β2-Microglobulin is found with hemodialysis-
associated amyloidosis. Calcitonin is a precursor to local am-
2 0 A Cystic fibrosis can be accompanied by agenesis of yloid deposition in medullary thyroid carcinomas. Excessive
the vas deferens, a common finding that leads to infertility. light chains predispose to amyloid deposition with multiple
With good medical care, patients with cystic fibrosis are living myeloma. Transthyretin can be associated with systemic se-
longer, and childbearing becomes an issue. Disorders of nile amyloidosis.
fibroblast growth factor receptor (FGFR) can include dwar
fism. Glucose-6-phosphate dehydrogenase (G6PD) deficiency PBD9 257–262 BP9 153–158 PBD8 251–253 BP8 168
results in hemolysis on exposure to oxidants such as antima-
larial drugs (e.g., primaquine). The HFE gene is abnormal in 2 4 C The reddish-purple lesions are typical of Kaposi
hereditary hemochromatosis; however, the patient is young sarcoma in a patient with wasting syndrome, oral thrush,
for the onset of this disease. NF1 (neurofibromatosis) is and lymphopenia characteristic of HIV infection with AIDS.
C H A P T E R 3 0 Final Review and Assessment 4 8 3
Hepatitis C virus is unlikely to produce skin lesions or lym- 2 8 D Patients with hepatitis C infection can develop
phopenia of this degree. Herpes simplex virus infections chronic hepatitis with persistently elevated liver enzymes.
may be seen more frequently in HIV infection, but the lesions Some patients with hepatitis C develop a mixed cryoglob-
are typically vesicular and are located in the perioral or peri- ulinemia with a polyclonal increase in IgG. Renal involve-
anal regions. Hansen disease, caused by Mycobacterium leprae ment is common, with either nephrotic or nephritic features.
infection, may produce a faint reddish rash that fades, fol- Cryoglobulinemic vasculitis leads to skin hemorrhages and
lowed by hypopigmentation or anesthesia of affected skin ulceration. Autoimmune hemolytic anemia can lead to a pre-
and sometimes nodular deforming lesions developing over dominantly indirect hyperbilirubinemia. Although hepato-
years. Staphylococcal skin infections tend to produce local- cellular carcinoma may complicate hepatitis C infection, a
ized abscesses, such as furuncles and boils. Streptococcal mass lesion would be seen on CT scan, and the alkaline phos-
skin infections may manifest as abscesses or as cellulitis. phatase level usually is elevated when an intrahepatic mass
is present. Chronic liver disease may complicate hereditary
PBD9 253–254 BP9 152 PBD8 246–247 BP8 164–165, 374–376 hemochromatosis, but these patients usually do not have
hepatitis C, and the skin has a slate color, not purpura. Mul-
25 A Lyme arthritis is suggested by meningitis, carditis, tiple myeloma can increase the serum globulin and produce
and a past history of erythema chronicum migrans. The ar- renal disease, but hepatitis is usually not part of myeloma;
thritis may appear weeks to a couple of years after a bite vasculitis likewise is not part of myeloma.
from the vector, the deer tick (Ixodes), and can be migratory
and involve the large joints. Tuberculosis rarely can produce PBD9 833–835, 927 BP9 617–618 PBD8 847–848 BP8 643–644
a chronic arthritis associated with osteomyelitis of the large
joints, leading to ankylosis and deformity. Streptococci may 29 C The delay in onset after trauma is consistent with fat
cause an acute arthritis, although a polyarthritis with rheu- embolism to brain, and the figure shows the predominantly
matic fever owing to group A streptococcal infection can oc- white matter petechiae of brain purpura. Fat embolism caus-
cur along with carditis. Staphylococcus aureus causes an acute ing respiratory difficulty or neurologic findings typically
suppurative arthritis. Yersinia enterocolitica can cause entero- has an onset 1 to 3 days after trauma. The exact mechanism
pathic arthritis with an abrupt onset; a yearlong course is for development of these vascular lesions is unknown, but
possible in HLA-B27–positive individuals. vascular occlusion with free fatty acid release and platelet
a ctivation play a role. Central pontine myelinolysis occurs
PBD9 381–382, 1214 BP9 789–790 PBD8 377–378 BP8 824 when hyponatremia is rapidly corrected, leading to white
matter edema most marked in the tightly packed crossing
2 6 A Alzheimer disease is progressive over years, and the fibers of the pons. Diffuse axonal injury can occur as a result
brain becomes decreased in size, with narrower gyri and of trauma, but symptoms and signs should appear soon after
widened sulci, usually in all lobes except the occipital lobes. the injury, and the white matter lesions are often microscop-
The atrophy leads to ex vacuo ventricular dilation. Micro- ic. A ruptured aneurysm is usually not related to trauma,
scopically, there are neocortical neuritic plaques with Aβ and most of the hemorrhage is at the base of the brain. Be-
amyloid cores. Absence of Betz cells may be seen in amyo- cause she is afebrile, an abscess is unlikely, and the CT scan
trophic lateral sclerosis, in which there is progressive mus- did not show a focal lesion. Viral meningitis can produce
cular weakness. Alzheimer type II cells, despite the eponym, brain edema, and herpes simplex viral infection can produce
are not part of Alzheimer disease, but are seen with increased hemorrhage, but there is no relationship to trauma, and there
blood ammonia levels as a consequence of hepatic failure— should be leukocytosis in the CSF with infection.
hepatic encephalopathy. Arteriolosclerosis can occur in asso-
ciation with hypertension. Red neurons are seen with acute PBD9 128 BP9 91 PBD8 126–127 BP8 99
infarction. Spongiform change is most likely to occur in a
rapidly progressive dementia (over weeks to months), such 30 A Translational research takes an idea from bench to
as Creutzfeldt-Jakob disease. bedside. The mechanism described is that of apoptosis, or in-
dividual cell death. Turning on apoptosis within cancer cells
PBD9 1287–1292 BP9 836–838 PBD8 1313–1317 BP8 891–893 would be a useful pharmacologic effect to cause the tumor to
self-destruct. The other listed conditions would not benefit
27 E The findings are most typical of gouty arthritis. Gout from induction of apoptosis to a similar degree.
can lead to renal failure and to tophaceous deposits in soft
tissues and joints, and it is often accompanied by hyperlip- PBD9 52–58 BP9 19–22 PBD8 25–29 BP8 19–22
idemia. Calcium pyrophosphate dihydrate deposition dis-
ease is more common in elderly individuals and usually is 31 D The MR image shows multiple areas of signal in-
asymptomatic; the knees are most often affected, and soft- tensity representing white matter plaques of demyelination
tissue deposition of the crystals away from joints is unlikely. typical of multiple sclerosis, a disease that has various neu-
Cholesterol crystals form in joint cavities after trauma with rologic manifestations. The mean age at onset is 30 years, and
hemorrhage. Cystine crystals can be seen in the urine in cys- it rarely occurs after age 60 years. Optic neuritis, weakness,
tinosis, a rare inborn error of metabolism. Hydroxyapatite and sensory changes are frequent manifestations. Diabetes
crystals may be found in joints affected by osteoarthritis, mellitus can produce peripheral neuropathy and retinopa-
with either acute or chronic presentation. thy, but typically in a more symmetric fashion, and white
matter plaques are not present. Graves disease can lead to
PBD9 1214–1217 BP9 786–789 PBD8 1243–1246 BP8 820–823
4 8 4 U N I T I I Diseases of Organ Systems
hyperthyroidism with heat intolerance, but neurologic man- malignancies such as lymphomas, may produce a superior
ifestations are not frequent, and diarrhea is typically pres- vena cava syndrome, but neoplasms virtually never invade
ent. HIV infection can lead to HIV encephalitis, which can the arterial media, and bleeding from neoplasms is produced
involve white matter, although defined plaques are unlikely, from much smaller vessels. Takayasu arteritis can involve
and peripheral neuropathy is infrequent. Myasthenia gravis the aortic arch and lead to dissection, but this condition is
can produce generalized weakness, which becomes worse rare and is most likely seen in women younger than 30 years
with repetitive movement and is not focal; there are no white old. Syphilitic aortitis may produce aortic root dilation and
matter changes. Systemic lupus erythematosus can cause possible rupture, but this is much less common than aortic
cerebritis but without plaques of demyelination, and focal dissection resulting from hypertension and atherosclerosis.
neurologic deficits are an infrequent finding. Thromboangiitis obliterans (Buerger disease) is an uncom-
mon disorder that affects small to medium-sized arteries in
PBD9 1283–1285 BP9 832–834 PBD8 1310–1312 BP8 887–889 the arms and legs of middle-aged men who smoke.
32 D Spina bifida occulta is the mildest form of neural PBD9 501–505 BP9 344–348 PBD8 508–510 BP8 359–362
tube defect. It is characterized by defective closure of the ver-
tebral arches, but with intact meninges and spinal cord, and 3 5 C Pulmonary emphysema and gastritis are related
“closed” by skin and connective tissue. A radiograph may to smoking. Multiple malignancies are related to smoking,
show its presence in 20% of the population. Despite the lack including urinary tract urothelial carcinoma and renal cell
of an open defect, there is an increased risk for meningitis. carcinoma. α1-Antitrypsin (AAT) deficiency can explain em-
In an Arnold-Chiari malformation, there is a small poste- physema, but it would be panlobular, and AAT deficiency is
rior fossa and extension of the cerebellum into the foramen not associated with urinary tract neoplasia. Chronic alcohol-
magnum and a lumbar meningomyelocele. Dandy-Walker ism can explain gastritis, but not emphysema or carcinoma.
malformation is detected by ultrasound evidence of a cyst Aniline dyes increase the risk of urothelial carcinoma, but
in the fourth ventricle and agenesis of the cerebellar vermis. not of emphysema or gastritis. Vitamin C deficiency can lead
Meningomyeloceles are open neural tube defects. Tuberous to soft-tissue hemorrhages and bone pain, but not to carci-
sclerosis is a rare disease that causes firm hamartomatous noma or emphysema.
“tubers” in the cortex, and is not associated with neural tube
defects. PBD9 675–676, 766 BP9 464–466, 564–565 PBD8 684–687
BP8 484–487
PBD9 1256 BP9 822–823 PBD8 1284 BP8 872
3 6 A Addison disease with bilateral atrophy of the adre-
3 3 C Wilson disease (hepatolenticular degeneration) with nal cortex is most often idiopathic and leads to electrolyte
Kayser-Fleischer corneal rings results from a mutation in the changes owing to loss of mineralocorticoid secretion, mainly
gene encoding for a copper-transporting ATPase (ATP7B). aldosterone; when atrophy is marked, glucocorticoid secre-
Excessive copper deposition occurs, particularly in the liver, tion is diminished. Increased ACTH precursor hormones,
putamen, and cornea. Psychiatric and neurologic disturbanc- resulting from loss of feedback from cortisol production,
es are common in Wilson disease, and patients often develop stimulate skin melanocytes. Stress, including infections, may
chronic liver disease ranging from acute hepatitis to chronic precipitate an addisonian crisis. Loss of islets of Langerhans
hepatitis to cirrhosis. In α1-antitrypsin deficiency, there can is a feature of type 1 diabetes mellitus, with hyperglycemia
be chronic hepatitis and pulmonary emphysema, but there and possible ketoacidosis as complications. Loss of releas-
are no neurologic changes. Cystic fibrosis can lead to pul- ing or inhibiting hormones from the hypothalamus affects
monary disease and pancreatic insufficiency. Galactosemia the pituitary and leads to multiple endocrinopathies, but not
can lead to liver disease and cirrhosis in early childhood. In specifically to loss of ACTH. Parafollicular C cells of the thy-
its most severe form, Gaucher disease from glucocerebrosi- roid produce calcitonin, which plays a minor role in calcium
dase deficiency can lead to neurologic deterioration, but it homeostasis. The pineal gland produces melatonin, which
does not lead to chronic liver disease. Von Gierke disease is is involved in circadian rhythms, but is not significant in
a form of glycogen storage disease that does not commonly disease states. Loss of thyroid hormone from follicular epi-
progress to cirrhosis. thelium leads to hypothyroidism typified by modest weight
gain, coarse and dry skin, and constipation, but without sig-
PBD9 849–850 BP9 630–631 PBD8 863–864 BP8 656–657 nificant electrolyte disturbances.
3 4 A An aortic dissection can extend proximally to PBD9 1130–1132 BP9 757–759 PBD8 1154–1157 BP8 793–795
envelope and partially occlude the great vessels. Proximal
dissections may result in minimal or no chest pain. Blood 37 A Prolactinoma is the most common tumor of the ante-
has dissected into the mediastinum, causing widening, and rior pituitary. Macroadenomas produce homonymous hemi-
into the pericardial cavity, causing tamponade. Risk factors anopsia and can secrete prolactin to cause gynecomastia. A
include hypertension and atherosclerosis. In addition, cys- carcinoid tumor can produce various hormones, but not pro-
tic medial necrosis makes aortic dissection a serious risk in lactin. Medullary thyroid carcinomas can produce calcitonin,
individuals with Marfan syndrome. A bicuspid aortic valve which has a minimal effect on calcium homeostasis. Pheo-
leads to aortic valvular stenosis, but not to aortic rupture. chromocytomas can produce excess catecholamines, most
Neoplasms involving the mediastinum, typically hematologic often manifested by hypertension. Renal cell carcinomas
C H A P T E R 3 0 Final Review and Assessment 4 8 5
may produce various paraneoplastic syndromes, most often 41 A Stevens-Johnson syndrome (SJS) is a severe form of
polycythemia, hypercalcemia, and Cushing syndrome, but erythema multiforme that can complicate infections and drug
not hyperprolactinemia. Likewise, small cell anaplastic (oat therapy. Sulfonamides, allopurinol, phenytoin, and carbam-
cell) lung cancers of neuroendocrine origin can produce para- azepine are the most likely drugs to be associated with SJS.
neoplastic syndromes, most often Cushing syndrome and the Cytotoxic (CD8+) lymphocytes mediate SJS through epider-
syndrome of inappropriate antidiuretic hormone secretion. mal cell necrosis. Eosinophils are common in allergic reac-
tions, including drug allergies, but most of these reactions
PBD9 1076–1079 BP9 719–720 PBD8 1103–1104 BP8 755 are accompanied by urticaria and erythema of short dura-
tion, without blistering or desquamation. Langerhans cells
3 8 E The child has trisomy 21 (Down syndrome) and has and macrophages are antigen-presenting cells in the epider-
developed acute leukemia as a complication. The 45,X karyo- mis and dermis that do not directly cause toxic damage to
type is seen in Turner syndrome only in females. The normal surrounding cells. Neutrophilic exudates are not a feature of
46,XY karyotype is unlikely with the constellation of anoma- SJS, although a leukocytoclastic vasculitis with purpura is a
lies present in this case. Trisomies 13 and 18 are far less likely form of drug reaction. Natural killer cells are part of innate
than trisomy 21 to be associated with long-term survival; immunity and do not participate directly in drug reactions.
affected children are more likely to have severe anomalies.
The 47,XXY karyotype of Klinefelter syndrome is associated PBD9 1164–1165 BP9 853–854 PBD8 1189 BP8 839–840
with nearly normal–appearing males of normal intelligence.
42 C Letterer-Siwe disease is an acute disseminated form of
PBD9 161–163 BP9 237–238 PBD8 161–163 BP8 244 Langerhans cell histiocytosis. Acute lymphoblastic leukemia
generally produces an elevated WBC count, and cutaneous
3 9 C About 10% of individuals with autosomal dominant and skeletal manifestations are rare. Gaucher disease, an
polycystic kidney disease (ADPKD) have a berry aneurysm autosomal recessive condition resulting from diminished
of the circle of Willis, which may be complicated by rupture glucocerebrosidase activity, has cells with cytoplasm that
and hemorrhage into the subarachnoid space. The cysts of resembles crinkled tissue paper, and the course is not as ag-
ADPKD may appear in the liver, and rarely in the pancreas. gressive. Leishmania donovani can cause visceral leishmani-
The cysts in adult-onset medullary cystic disease are central- asis, but the amastigotes infiltrating the marrow are not posi-
ly located in the kidney. Although renal failure does occur tive for CD1a, and the course is usually not as aggressive.
in middle age, similar to ADPKD, the kidneys are small and Multiple myeloma is seen in older adults, and although lytic
shrunken, and there are no cysts in other organs. Abnormal bone lesions are common, they are caused by infiltrates of
renal resorption of amino acids, including cystine, may lead plasma cells. Forms of myelodysplastic syndrome are seen
to formation of cystine crystals and stones in the urine; ma- in older adults, with myeloid cells that do not mark for CD1a
ple syrup urine disease and severe liver disease may cause but are accompanied by numerous ringed sideroblasts in the
such a finding. Granulomatosis with polyangiitis (ANCA- marrow; some cases progress to acute myelocytic leukemia.
associated vasculitis) can affect multiple organs, principally
the kidneys and lungs, but it does not produce cystic disease. PBD9 621–622 BP9 449 PBD8 631–632 BP8 467–468
Diabetic nephropathy includes nephrosclerosis, glomerulo-
sclerosis, pyelonephritis, and papillary necrosis, but not cys- 43 C Myositis ossificans is an uncommon, exuberant re-
tic disease. Polyarteritis nodosa may produce small microan- pair reaction following soft-tissue trauma to muscle in which
eurysms of arteries, typically in the kidneys, and may affect there is metaplastic bone formation. The keys to diagnosis
multiple organs, but cystic disease is not seen. are the location within soft tissue, calcification beginning at
the periphery, and decrease in size over time. Gouty tophi
PBD9 945–947, 1269–1271 BP9 542–544, 817–818 PBD8 956–959 can form in soft tissues, but there is typically a history of
BP8 569–570, 866 gouty arthritis first, and the lesions do not calcify. A hem-
arthrosis forms with joint trauma and hemorrhage in and
4 0 D Scurvy from vitamin C deficiency is manifested by a around the joint capsule, but does not involve calcification.
decrease in synthesis of collagen peptides from inadequate An osteochondroma is a bony exostosis projecting from
hydroxylation of procollagen. Diminished collagen synthe- bone into soft tissue. An osteosarcoma that rarely arises in
sis affects bone matrix formation, vascular integrity, and soft tissue must be distinguished from myositis ossificans;
epithelial function. There is bleeding into joints and soft tis- the latter is characterized by the mature shell of bone, lack
sues with minimal trauma. Diminished carbonic anhydrase of enlargement, and lack of bone or soft-tissue destruction.
levels are seen in some forms of ostepetrosis with risk for Polymyositis involves inflammation with degeneration and
fracture, but not the other findings. Hemophilia A, which in regeneration of muscle fibers, but there is no mass effect and
some cases can be due to an acquired inhibitor of factor VIII, no calcification.
leads to hemorrhage into soft tissues with hemarthroses and
joint deformities, but this condition is typically X-linked and PBD9 38 BP9 793 PBD8 1251 BP8 833 AP3 Figs. 17-88, 17-91
unlikely to affect girls, and skin and bone are not primarily
involved. Mutations in fibroblast growth factor receptor un- 44 E In “classic” polyarteritis nodosa, HBsAg is positive
derlie some forms of dwarfism. Vitamin D deficiency could in about one third of cases. The mesenteric artery angio-
produce the bone deformities, but there is reduced calcifica- gram reveals focal distal occlusions and microaneurysms of
tion, and anemia and hemorrhage are not found. branches of the superior mesenteric artery. Antimitochon-
drial antibody is seen in primary biliary cirrhosis. ANCA
PBD9 442–443 BP9 301–302 PBD8 437–438 BP8 312–313
4 8 6 U N I T I I Diseases of Organ Systems
is associated with “microscopic” polyarteritis, but not with typical of syndromes in which an immunodeficiency state is
classic polyarteritis. The ANA test result is positive in a wide present, such as AIDS and large cell lymphoma with BCL6
variety of autoimmune diseases, principally systemic lupus mutation. Osteomas may be seen in Gardner syndrome with
erythematosus, which can affect the kidney with glomeru- the adenomatous polyposis coli (APC) gene. Renal cell carci-
lonephritis, not typically vasculitis. Cryptococcal antigen noma may be seen in von Hippel–Lindau disease owing to
can be detected in CSF of patients with meningitis, usually mutation in the VHL gene.
immunocompromised patients. Histoplasma capsulatum anti-
body may be detected in individuals with prior exposure to PBD9 1136–1137 BP9 761–762 PBD8 1162 BP8 798–799
this agent, which mainly causes pulmonary disease.
48 D His pneumoconiosis (with progressive massive fibro-
PBD9 509–510 BP9 352 PBD8 514–515 BP8 365–366 sis) is producing restrictive lung disease. Silicosis occurs
from prolonged and extensive exposure to inorganic dusts
4 5 A This form of adrenogenital syndrome is character- in occupations such as mining. Carbon monoxide poisoning
ized by 21-hydroxylase deficiency and salt wasting caused produces hypoxemia without pathologic changes to lung
by a block in cortisol synthesis and an increase in ACTH tissues. Fungal hyphae may produce either an allergic re-
secretion stimulating increased androgen production. Islet sponse or a hypersensitivity pneumonitis. Plant pollens are
cell adenomas may secrete various hormones, often insulin, most often associated with episodic atopic asthma. Sulfur
glucagon, or somatostatin, which do not produce virilizing dioxide contributes to chronic bronchitis. Wood dusts tend
signs. Pituitary adenomas may destroy remaining pituitary to produce bronchoconstriction.
function and lead to hypopituitarism, but a microadenoma
is unlikely to do this, and the features in this case suggest PBD9 690 BP9 476 PBD8 697–698 BP8 498–499
increased ACTH secretion. Neuroblastomas can be seen in
young children and arise in the adrenal or extra-adrenal 4 9 F Mixed connective tissue disease has overlapping fea-
paraganglia, but their hormonal output may produce only tures of systemic lupus erythematosus (SLE), scleroderma,
hypertension. Craniopharyngiomas are typically seen in polymyositis, and rheumatoid arthritis. ANCA is most likely
adolescence to young adulthood and are destructive lesions to be seen in vasculitides such as ANCA-associated granu-
without hormonal output. Medullary carcinoma of the thy- lomatous vasculitis or microscopic polyarteritis. Antibodies
roid is a tumor in adults that can produce calcitonin. to cyclic citrullinated peptide (anti-CCP) have greater than
99% specificity for rheumatoid arthritis, and these patients
PBD9 1127–1128 BP9 756–757 PBD8 1152–1154 BP8 792–793 are more likely to have severe disease. Antihistone antibod-
ies are most characteristic of drug-induced SLE. Anti-Smith
46 F Celiac disease is complicated by dermatitis herpeti- antibodies are very specific for SLE. Thyroid peroxidase an-
formis in this man. Antigliadin, antitransglutaminase, and tibodies are seen in autoimmune thyroid disorders, such as
antiendomysial antibodies can be detected. The jejunal bi- Hashimoto thyroiditis and Graves disease.
opsy specimen shows mucosal flattening and increased in-
traepithelial lymphocytes. Individuals who have HLA-DQ2 PBD9 231 BP9 135 PBD8 226 BP8 151
or HLA-DQ8 are more likely to develop these findings. With
a gluten-free diet, the skin lesions resolve in some patients. 50 D This family has fragile X syndrome. Anticipation
Antibodies to desmoglein 3, a desmosome protein, are pres- occurred, with premutations of limited triple repeat expan-
ent in pemphigus vulgaris, a vesicular disease of older adults sions present in the first two generations, whereas later gen-
without gastrointestinal tract involvement. Cyclic citrulli- erations had full mutations with larger CGG expansions. The
nated peptide antibodies are characteristic for rheumatoid FMR1 gene encodes for familial mental retardation protein
arthritis. Antibodies to double-stranded DNA are highly (FMRP) expressed most abundantly in brain and testis, ac-
specific for systemic lupus erythematosus (SLE), which pro- counting for macro-orchidism in the latter. Absence of this
duces erythematous rashes without vesicles. Antihistone protein in brain leads to increased mRNA translation that
antibodies are most characteristic of drug-induced SLE. An- affects synaptic junctions and their function. The FMRP pro-
ti-RNP antibodies are seen in mixed connective tissue dis- tein is widely expressed in other tissues such as those listed,
ease, which has elements of SLE, scleroderma, rheumatoid but their function is not as markedly affected as brain and
arthritis, and polymyositis. Antibodies to type IV collagen testis.
are seen in Goodpasture syndrome, which does not involve
skin rashes. PBD9 169–171 BP9 241–243 PBD8 169–171 BP8 248–250
PBD9 782–783, 1170–1171 BP9 577–579, 861 PBD8 795–796, 1196 5 1 B Thromboembolic events in women of later reproduc-
BP8 611, 847 tive years, and the hepatic adenoma shown here, are com-
plications of oral contraceptive use. Note the green color
4 7 A Multiple endocrine neoplasia type 1 (MEN 1) in this (biliverdin) indicating that this neoplasm, derived from he-
case is associated with a gastrinoma (arising either in the is- patocytes, is producing bile. Allopurinol and sulfonamides
lets or in the small intestine), a parathyroid lesion (adenoma are associated with hepatic granuloma formation. Aspirin
or hyperplasia), and a prolactinoma. Medullary carcinoma use in children has been associated with Reye syndrome with
and pheochromocytoma are more typical of MEN 2 with microvesicular steatosis. Isoniazid has been associated with
RET gene mutation. Non-Hodgkin lymphomas are more acute or chronic hepatitis. Phenacetin and acetaminophen
C H A P T E R 3 0 Final Review and Assessment 4 8 7
use have been associated with analgesic nephropathy, and large multimers of vWF. The metalloproteinase is referred
excessive acetaminophen use may produce acute massive to as ADAMTS 13 (a disintegrin and metalloproteinase, with
hepatic necrosis. thrombospondin 1–like domains). In most patients with
TTP, plasma ADAMTS 13 activity is less than 5% of normal.
PBD9 867–869 BP9 636 PBD8 415 BP8 293–294 The patient’s hemoglobin concentration is not low enough
to justify transfusion of RBCs. Giving platelets to a patient
5 2 D Risk factors for HELLP (hemolysis with elevated liv- with TTP would “add fuel to the fire” because the platelets
er enzymes and low platelets) syndrome, a variant of severe would cause more thrombi to form, resulting in further or-
preeclampsia, include nulliparity, advanced maternal age, gan damage. Simple pressor agents, such as dobutamine, are
diabetes mellitus, preexisting hypertension, a prior history not primary therapy. Surgery is not indicated because the
of preeclampsia, and renal disease. Patients with HELLP injury is occurring in the small vasculature of many organs.
syndrome may progress to disseminated intravascular co- Prednisone may be given to a subset of patients who do not
agulation. Emergent delivery is indicated. Abruptio placen- respond to plasmapheresis.
tae is an acute event marked by severe abdominal pain and
vaginal bleeding. Hepatic vein thrombosis in Budd-Chiari PBD9 659–660 BP9 453–454 PBD8 669–670 BP8 472–473
syndrome can produce liver necrosis with elevated enzymes;
pregnancy is a risk factor, but this does not explain the 55 C Budd-Chiari syndrome is a rare condition that can
neurologic and renal findings. Likewise, a dilated cardiomy- complicate pregnancy or the postpartum state. Hepatic ve-
opathy that can occur in pregnancy does not explain these nous occlusion leads to hepatomegaly with severe centri-
findings. In hydatidiform mole, preeclampsia is more likely, lobular congestion and necrosis, much more pronounced
but 30 weeks is a long time to have it, and a fetus would than the typical nutmeg liver of chronic passive congestion
not be present. Acute fatty liver of pregnancy may resemble with right-sided heart failure. Biliary tract obstruction with
Reye syndrome (a disease that occurs in children) and may choledocholithiasis would increase the serum bilirubin to a
be preceded by preeclampsia. Sheehan syndrome is postpar- greater degree than seen in this patient, and hepatomegaly
tum pituitary necrosis leading to hypopituitarism. is unlikely. Hepatic adenomas, which can be associated with
use of oral contraceptives, are mass lesions, usually several
PBD9 1037–1039 BP9 703–704 PBD8 875 BP8 737–738 centimeters in size. At 12 weeks’ gestation, with a fetus pres-
ent, choriocarcinoma is very unlikely, and a marked increase
5 3 E The findings are those of infectious endocarditis, and in liver enzymes is unlikely. Acute fatty liver of pregnancy
the needle track in the left arm suggests injection drug use with microvesicular steatosis produces a more uniform den-
as the risk factor. These individuals can have right-sided sity with hepatomegaly, a rare condition that is usually seen
and/or left-sided valvular lesions. The vegetations are likely in the third trimester of pregnancy.
to embolize, and the septic emboli can lead to infection or
infarction of multiple organs from left-sided lesions and of PBD9 863–864 BP9 634 PBD8 872–873 BP8 662
the lungs from right-sided lesions. The pulmonary nodule is
likely a lung abscess. The patient probably has acute pyelo- 5 6 B In common variable immunodeficiency (CVID),
nephritis from hematogenous infection. Candida albicans and there are normal numbers of T cells with normal to low
Cryptococcus neoformans may cause endocarditis in immuno- numbers of B cells, and there is hypogammaglobulinemia
compromised individuals. Escherichia coli is a likely cause of with decreased IgG and possibly other immunoglobulin
ascending urinary tract infections with pyelonephritis, but it types. CVID occurs in young adults of both sexes, causing in-
is an uncommon cause of endocarditis. Listeriosis most of- creased bacterial infections and giardiasis and recurrent her-
ten results from food or water contamination and can lead to pes simplex (and herpes zoster) infections. The mechanisms
sepsis with meningitis, but rarely endocarditis. Streptococ- are diverse and include failure of B-cell maturation to plasma
cal infections are more likely to cause endocarditis in indi- cells, excessive T-cell suppression, and defective T helper cell
viduals with preexisting valvular heart disease, and viridans function. Mutations in genes encoding NADPH oxidase pro-
streptococci are most often implicated. Yersinia enterocolitica teins produce chronic granulomatous disease and recurrent
can produce enterocolitis, not endocarditis (this organism infections with Aspergillus, Staphylococcus, Serratia, Nocardia,
can persist in stored blood and cause transfusion-related and Pseudomonas. In hyper-IgM syndrome, mutations in the
sepsis). CD40 ligand induce failure in B cells, with low IgG, IgA,
and IgE levels, but increased IgM; in infancy and childhood,
PBD9 559–561 BP9 392–394 PBD8 567–568 BP8 406–407 there is increased risk of severe infections with bacterial and
viral agents and opportunistic agents, such as Pneumocystis
5 4 E Thrombotic thrombocytopenic purpura (TTP) can jiroveci. Mutations in CD18, the common β chain of integ-
present with the classic pentad of neurologic changes, fever, rins, which aid in binding of leukocytes, lead to leukocyte
thrombocytopenia, microangiopathic hemolytic anemia, and adhesion deficiency with leukocytosis, but with absence of
decreased renal function. The pathogenesis of TTP is relat- suppurative inflammation in areas of tissue necrosis and ul-
ed to von Willebrand factor (vWF). Monomers of vWF are ceration caused by Staphylococcus aureus and gram-negative
linked by disulfide bonds to form multimers with various enteric bacteria. In severe combined immunodeficiency
molecular masses that range to millions of daltons. A vWF- (SCID), half of cases result from an X-linked m utation for
cleaving metalloproteinase in plasma normally prevents the the common γ chain of IL-2, a receptor for many cytokines
entrance into the circulation (or persistence) of unusually needed for T-cell development, and the other half of cases
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Robbins and Cotran Review of Pathology ( PDFDrive ) (1)
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