Nbme 30 2021 A

Exam Section 1: Item 1 of 50 National Board of Medical Examiners^
Comprehensive Basic Science Self-Assessment
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1 . Shortly after delivery a full-term male newborn is found to have black hair with a white forelock . His mother, a brunette also has a white forelock and wears hearing aids. Physical examination shows heterochromia of irides . Otoacoustic emissions testing and
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brain stem auditory evoked responses show bilateral sensorineural hearing loss. Which of the following is the most likely cause of the findings in this patient?
A ) Abnormal neural crest development

B ) Abnormality of connexins
C ) Deficiency of homogentisic acid oxidase activity
D } Deficiency of tyrosinase activity
E ) Failure of internalization of melanin granules by keratinocytes
F ) Failure of melanosome transportation along dendrites
Correct Answer : A .
Abnormal neural crest development leads to Waardenburg syndrome. Waardenburg syndrome is a syndrome of patchy depigmentation of the skin , hair irises and cochlear dysfunction that primarily illustrates an autosomal dominant inheritance pattern . Because of
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genetic mutations of genes encoding transcription factors , neural crest cells do not properly differentiate into melanoblasts ( melanocyte precursors ) , or melanoblasts do not migrate to their appropriate location. Patients typically have a white forelock and eyelashes ,
depigmented skin patches , iridic heterochromia , and sensorineural deafness . The eyes may also be laterally displaced. The clinical diagnosis may be confirmed with genetic testing . Treatment includes audiologic evaluation and genetic consultation .
Incorrect Answers : B, C , D: E , and F.
An abnormality of connexins ( Choice B) would lead to abnormal formation of the plasma membrane channels of diverse cell types . Different combinations of sensorineural hearing loss, ichthyosis alopecia , and peripheral neuropathy may occur. Depigmentation
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would be atypical.
Deficiency of homogentisic acid oxidase activity ( Choice C) would lead to decreased metabolism of the amino acids phenylalanine and tyrosine , which instead degrade into homogentisic acid . Homogentisic acid accumulates in the skin and joints , causing increased
pigmentation and arthritis, respectively. Depigmentation would be atypical .
Deficiency of tyrosinase activity (Choice D) occurs in oculocutaneous albinism which presents with uniformly hypopigmented hair and skin (versus the patchy depigmentation of Waardenburg syndrome) and eye abnormalities ( eg , iris hypopigmentation refractive
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errors, nystagmus ) fn tyrosinase deficiency, melanocytes are unable to synthesize melanin from the amino acid tyrosine . Iridic heterochromia and sensorineural deafness would be atypical.
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Failure of internalization of melanin granules by keratinocytes ( Choice E) as well as the failure of melanosome transportation along dendrites ( Choice F) would lead to decreased pigmentation of keratinocytes , the primary cell type of the epidermis. These
abnormalities would likely lead to uniform depigmentation (versus the patchy depigmentation of Waardenburg syndrome ) , and iridic heterochromia and sensorineural hearing loss would be atypical .
Educational Objective: Waardenburg syndrome is a syndrome of patchy depigmentation of the skin, lair, irises , and cochlear dysfunction that results from a defect in the differentiation of neural crest cells into melanocytes. Patients typically present with a white
forelock and eyelashes , depigmented skin patches, iridic heterochromia , and sensorineural hearing loss .
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2 . During an experiment , a solution of mixed fatty acids is injected into the duodenum of an experimental animal . Under these conditions the clearance rate of an intravenous glucose load from the circulation is doubled . In contrast, an injection of an equal
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volume amount of 0.9% saline into the duodenum has much less effect on the plasma clearance rate of glucose. These findings are most likely caused by the secretion of which of the following hormones?
A ) Gastrin
B ) Glucose-dependent insulinotropic peptide
C ) Motilin
D ) Secretin
E ) Somatostatin
Correct Answer : B .
Glucose-dependent insulinotropic peptide (GIF) Is secreted by K cells in the duodenum and jejunum and functions to decrease gastric acid production and stimulate insulin release from the pancreas . Its secretion is promoted by the presence of fatty acids, amino
acids , and intestinal glucose . While serum glucose also stimulates insulin secretion by the pancreas , the effect of intraluminal glucose on GIF and subsequent insulin secretion leads to increased concentrations of insulin compared to parenteral glucose
administration. Insulin promotes peripheral tissue uptake of glucose , glycolysis , glycogen synthesis , protein synthesis , and fatty acid synthesis , resulting in decreased glucose concentration in the serum .
Incorrect Answers : A, C , D . and E.
Gastrin ( Choice A) is produced by G cells in the gastric antrum and stimulates parietal cells within the gastric body to produce hydrochloric acid . Gastric acid has no effect on serum glucose concentration .
Motilin (Choice C ) is secreted by the small intestine and stimulates intestinal peristalsis . IVlotilin receptors are targeted by erythromycin and metodopramide, used therapeutically in gastroparesis .
Secretin ( Choice D ) is produced by duodenal S cells . It promotes the release of bi car bon ate-rich pancreatic secretions and bile and inhibits gastric acid production.
Somatostatin ( Choice E) is a regulatory peptide secreted by D cells of the pancreas and gastrointestinal mucosa that inhibits gastric acid and pepsinogen secretion, gallbladder contraction , and insulin and glucagon release. Somatostatin would have an indirect
effect on glucose through counter regulatory action of both insulin and glucagon .
Educationa Objective: Glucose- dependent insulinotropic peptide ( GIF) is secreted by K ceMs in the duodenum and jejunum, and it functions to decrease gastric acid production and stimulate insulin release from the pancreas . Insulin promotes the peripheral tissue
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uptake of glucose and hepatic glucose storage , resulting in a decreased glucose concentration in the serum .
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3 . A 53 -year- old man comes to the physician because of a 6- day history of shortness of breath , cough, and pleuritic chest pain. His temperature is 38.9DC (102°F): and respirations are 35 / min. Sputum is purulent and rust colored Physical examination shows
decreased breath sounds : and crackles are heard at the left base . A Gram stain of sputum shows gram- positive diplococci. A chest x-ray shows left-sided lobar consolidation . Which of the following anatomic structures most likely allowed rapid spread of
organisms between alveoli to involve the entire left lobe in this patient?
A ) Alveolar capillaries
B ) Germinal centers
C ) Lymphatic capillaries
D ) Pores of Kohn
E ) Vascular sinusoids
Correct Answer : D .
The pores of Kohn form connections between alveoli and are present in norma! lung tissue. They are composed , at least in part of type II alveolar cells and allow for the passage of air fluid phagocytes , and in the setting of pneumonia , bacteria between adjacent
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alveoli . By allowing equilibration between adjacent alveoli the pores of Kohn aid in normal oxygenation and in the prevention of atelectasis . However infectious organisms and inflammation may also spread between adjacent alveoli through these apertures .
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Incorrect Answers : A . B C . and E.

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Alveo: ar capillaries ( Choice A ) surround each alveolus and are crucial for gas exchange . However they do not provide a direct connection between adjacent alveoli, provided that the alveolar and capillary endothelia remain intact .
Germinal centers ( Choice B) allow for the development of B lymphocytes and are important in mounting an adaptive immune response to pulmonary pathogens 1 hey do not form connections between alveoli .
Lymphatic capillaries ( Choice C ) allow for the drainage of interstitial fluid from the lung parenchyma to the lymphatic ducts and eventua ly to the heart . These passages do not form direct anastomoses between adjacent alveoli .
Vascular sinusoids (Choice E) are present in hepatic tissue and create anastomoses between the portal and systemic circulation, allowing for the exchange of nutrients with hepatocytes. They are not present in pulmonary tissue .
Educationa Objective : The pores of Kohn form connections between alveoli and are present in normal lung tissue. They allow for the passage of air, fluid , phagocytes, and , in the setting of pneumonia , bacteria between adjacent alveoli .
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4 . A female newborn is bom at 39 weeks' gestation following an uneventful pregnancy The Apgar scores are 10 at 1 and 5 minutes , respectively. The newborn is at the 50th percentile for length and 25th percentile for weight . She has normal morphologic
features The parents are told she has an enzyme defect that , if left untreated will result in failure to attain early developmental milestones: microcephaly: hyperactivity. seizures: intellectual disability, and a mousy odor of the skin and urine The patient' s diet
needs to contain which of the following to provide substrate for catecholamine production?
A ) Dihydroxyphenylalanine
B ) Dopamine
C ) Epinephrine
D ) Norepinephrine
E ) Phenylalanine
F ) Tyrosine
Correct Answer F
Tyrosine supplements are required for catecholamine production in this patient with phenylketonuria (PKU). PKU results from a deficiency in the enzyme phenylalanine hydroxylase ( PAH ) that converts phenylalanine to tyrosine. Deficiency results in accumulation of
phenylalanine and its metabolites phenylacetate and phenyllactate. Rarely mutations in enzymes that either produce or recycle tetrahydrobiopterin (BH J , which is a cofactor for PAH , can have similar c inica! manifestations as classic PKU . Phenylalanine is a
precursor to tyrosine , and tyrosine is used to synthesize catecholamines such as dopamine , epinephrine, and norepinephrine . Tyrosine is converted to dihydroxyphenylalanine by tyrosine hydroxylase, followed by conversion to dopamine by DOPA -decarboxylase.
Dopamine can subsequently be converted to norepinephrine and methylation of norepinephrine results in formation of epinephrine . Patients with PKU from PAH deficiency require supplementation with tyrosine to bypass the dysfunctional enzymatic step of
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converting phenylalanine to tyrosine.
Incorrect Answers : A . B C . D, and E

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Dihydroxyphenylalanine ( Choice A ) , abbreviated as DOPA : is a precursor to dopamine and is formed via the action of tyrosine hydroxylase . This enzymatic pathway is functional in patients with PKU so supplementation with DORA is not required. Similarly ,
dopamine (Choice B) is created from DORA by the enzyme DORA decarboxylase , while epinephrine ( Choice C ) and norepinephrine ( Choice D ) are made from dopamine by separate enzymes: none of which are deficient in PKU . Supplementation of tyrosine is
sufficient to allow for normal synthesis of all of these catecholamines.
Phenylalanine ( Choice E ) would worsen the symptoms of PKU as the primary cause of this condition is the inability to convert phenylalanine to tyrosine .
Educational Objective: PKU commonly results from deficiencies in the enzyme phenylalanine hydroxylase which converts phenylalanine to tyrosine . Tyrosine in turn, is required for synthesis of the catecholamines dopamine , norepinephrine , and epinephrine.
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Supplementation with tyrosine effectively bypasses the defective enzyme and allows for the normal synthesis of catecholamines.
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5 . A 7 G -year- old woman comes to the emergency department because of a 6-hour history of moderate right low back and flank pain. Vital signs are within normal limits. Physical examination shows mild vertebromediastinal recess {costovertebral angle )
tenderness. Urinalysis shows no blood . A CT scan of the pelvis shows hydronephrosis with obstruction of the right ureter caused by external compression at the pelvic brim from a vascular structure. This patient most likely has an aneurysm of which of "he
following arteries ?
A ) Abdominal aorta
B ) Common iliac
C ) Femoral
D ) Inferior mesenteric
E ) Renal
The ureter courses from the renal pelvis to the urinary bladder. It initially descends through the lower abdomen anterior and medial to the psoas major. It then enters the pelvis and crosses immediately anterior to the bifurcation of the common iliac artery before
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continuing its descent anterior to the internal iliac artery. The ureters are commonly constricted at three locations : at the ureteropelvic junction at the crossing point over the common iliac artery: and at the vesicoureteral junction at the entrance to the bladder The
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ureter may be constricted by a vascular aneurysm of the common iliac artery and , additionally renal calculi tend to lodge at these three locations. Ureteral obstruction leads to hydroureteroneplirosis and possible postrenal kidney injury.
Incorrect Answers : A . Cr D, and E.
The abdominal aorta ( Choice A ) is located medial to the ureters , just anterolateral to the vertebral bodies . It bifurcates into the two common iliac arteries and does not come in direct proximity to either ureter. Abdominal aortic aneurysms are usually not of sufficient
size to cause ureferal obstruction .
The femoral artery ( Choice C ) is found in the thigh as a continuation of the external iliac artery. It does not come in proximity to the ureters . Femoral arterial aneurysms occur but are uncommon.
The inferior mesenteric artery ( Choice 0) originates from the abdominal aorta near the level of the third lumbar vertebra and provides arterial supply to the distal colon . As it is a midline structure , t does not come in dose proximity to the ureters.
The rena ! artery ( Choice E) supplies blood to the kidney and the proximal portion of the ureter While aneurysms of the renal artery may form , they are rare and are unlikely to obstruct the ureter.
Educational Objective: The ureter is commonly constricted at three sites: at the ureteropelvic junction , at the crossing point over the common iliac artery, and at the vesicoureteral junction at the entrance to the bladder. The ureter may be constricted by a vascular
aneurysm of the common iliac artery and , additionally, renal calculi tend to lodge at these three locations .
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6 . A 33 -year- old woman comes to the physician because of a 3-day history of nausea and light-headedness . Her last menstrual period was 5 weeks ago. She is apprehensive . Physical examination shows no abnormalities . Her serum p- human chorionic
gonadotropin concentration is increased . At this stage in the pregnancy, progesterone is most likety produced within which of the following structures?
A ) Corpus albicans
B ) Corpus luteum
C ) Pituitary gland
D ) Placental cytotrophoblast
E ) Placental syncytiotrophoblast
Pregnancy is suspected when there is a missed or delayed menstrual period During a normal menstrual period , follicle- stimulating hormone and iuteinizing hormone (FSH and LH , respectively ) concentrations increase and stimulate the developing follicle . The
follicle produces estrogen , which leads to proliferation of the endometrium in preparation for implantation of a fertilized ovum . As estrogen rises , a surge occurs , which in turn stimulates a surge in LH that causes ovulation . Immediately following ovulation , the corpus
luteum forms. The carpus luteum secretes progesterone to maintain the endometrial lining . If no implantation occurs , the corpus luteum degrades to the corpus albicans and estrogen and progesterone concentrations decrease , causing menstruation. However
during pregnancy, the placenta develops from embryo implantation . The placenta then begins to secrete human chorionic gonadotropin which acts to maintain the carpus luteum and its secretion of progesterone , which is necessary for maintenance of the
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pregnancy. As the placenta develops , it becomes primarily responsible for progesterone production around seven to ten weeks of gestation. As this patient is at five weeks of gestation , her progesterone production is still primarily performed by the corpus luteum .
Incorrect Answers : A . C , D, and E.
The carpus albicans (Choice A) is the degraded corpus luteum that develops because of the absence of embryo implantation. It does not secrete hormones .
The pituitary gland ( Choice G) is responsible for secreting FSH and LH . as we ; as prolactin and thyroid - stimulating hormone . While FSH and LH play a ro: e in the development of an ovarian follicle , the pituitary gland does not directly produce progesterone.
Placental cytotrophobtast ( Choice D ) is the inner layer of the chorion and ; s vital for the implantation of an embryo. It does not secrete hormones.
Placental syncytiotrophoblast (Choice E) is the outer layer of the chorionic villi and is responsible for secreting human chorionic gonadotropin which maintains the corpus luteum and its production of progesterone. It does not directly produce progesterone.
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Educational Objective: During pregnancy, progesterone Is produced by the corpus uteum for the first seven to ten weeks of gestation secondary to stimulation by human chorionic gonadotropin from the placental syncytiotrophoblast . after which time it is primarily
produced by the placenta .
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7 . A study is done to determine the relationship between use of oral contraceptives and cervical cancer. Study subjects include 50, 000 women who are using oraf contraceptives and 50,000 women who have had a tubal ligation. After 2 years of follow-up, the
rate of in situ cervical cancer is 18 per 10 , 000 in the oral contraceptive group and 3 per 10.000 ( p < 0.05) in the tubal ligation group. Which of the following is the estimated relative risk of cervical cancer among women who have had a tubal ligation compared
with women who use oraf contraceptives?
A) 3 - 50.000 = 0.00006
B) 3
- 1 3 = 0.17
C) 18
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3=6
D ) 1 8 - 3 1 0 = 17.7
E ) 1 8 - 3 = 15
F ) 18 + 3 = 21
G ) Indeterminable from the data given
Relative risk ( RR ) describes the difference in likelihood of the occurrence of a particular disease outcome between two groups of patients with or without a particular exposure . In this case: the outcome of cervical cancer in situ is compared between two exposures ,
the use of oral contraceptives or the use of tubal ligation for contraception. Calculations of relative risk are commonly performed in cohort studies. RR is calculated by dividing the fraction of patients with a positive exposure and who developed disease (a) amongst
all patients who were exposed which includes those exposed who did not develop disease (b ) , (a + b |by the fraction of patients with a negative exposure and who developed disease (c) amongst all patients who were not exposed which includes those who did not
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RR equal to 1.0 indicates that the disease outcome and the exposure are not related . In this case. RR of cervical cancer in situ among women who have had a tubal ligation compared with women wno use oral contraceptives is calculated as ( 3 / 10 ,000)
(13/10, 000) = 3 13 = 0.17 . -
develop disease (d ), ( c + d). RRtlius equals (a / ( a + b )) / (c / (c + d)). RR values greater than 1.0 indicate an increased risk for developing disease in association with the exposure, whereas values Jess than 1.0 indicate a reduced risk for developing disease , and
Incorrect Answers : A , C D . E F, and G .

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3 50, 000 = 0.00006 ( Choice A ) is an incorrect computation of the total fraction of women wiln a tubal ligation who developed cervical cancer in situ , as the data are presented per 10, 000 patients . Therefore , if the fraction of women with a tubal figation who
developed cervical cancer in situ were to be calculated , it would be 3/10 , 000 persons or 15/5 D: 000 in absolute numbers.
18
- 3 = 6 ( Choice C) computes the RR of developing of cervical cancer in situ among women who use oral contraceptives compared with women who have had a tubal ligation .
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18 - 3 10 = 17.7 ( Choice D) is not a meaningful computation in the context of the presented data and reflects a misinterpretation or a mathematical error.
18 - 3 = 15 ( Choice E ) if reflecting the numbers of cervical carcinoma in situ per 10.000 patients: would reflect the attributable risk to oral contraceptive use .
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18 + 3 = 21 ( Choice F) , if reflecting the numbers of cervical carcinoma in situ per 10.000 patients , would reflect the total risk within the overall study population .
Indeterminable from the data given (Choice G) is incorrect, as the relative risk can be computed from the data provided .
Educational Objective: Relative risk (RR ) describes the difference in likelihood of the occurrence of a particular disease outcome between two groups of patients with or without a particular exposure . RR is calculated by dividing the fraction of patients with a positive
exposure and who developed disease (a) amongst all patients who were exposed including those exposed who did not develop disease (b ) , (a + b ) by the fraction of patients with a negative exposure and who developed disease (c) amongst all patients who were
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not exposed which includes those who did not develop disease (d ), ( c + dj_ RR thus equals (a / ( aib )) / (c / ( c 4 d)).
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8 . A study is conducted to assess the accuracy of a new rapid test to detect a virulent bacterial infection. This infection has an 80% mortality rate if it is not identified early in its course ; however prompt administration of antibiotics decreases the mortality rate to
less than 5%. The risks of this antibiotic therapy are minimal. A total of 1 D. GOD participants are enrolled and undergo assessment with the newr test . The graph shows the distribution of infected and noninfected participants according to the results of the test.
Which of the following labeled points is most appropriate for use as the optimal diagnostic cut point for results of this test?
V)
E
ns
CL
O
c Not Infected
to
EX infected
o
CD
_Q
E5
=
A E
A)
B)
C)
D)
E)
Correct A ns wer : B .
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The cut point of the test should be set such that all persons with the infection result as positive so that there are few false negatives. The threshold should be set to maximize sensitivity, which equals the true positive test results divided by the sum of true positive
and false negative test results Therefore, as sensitivity approaches 1.0 , all patients who have the disease will be detected by the test (there will be no false negatives ). In this example , high sensitivity is critical, as the disease has an 80% mortality rate if not
detected and treated early. Therefore , a priority should be placed on sensitivity when deciding the cut point threshold for positive and negative results. Specificity is calculated by the true negative test results divided by the sum of true negative and false positive
results. Increasing sensitivity comes at the expense of specificity ; by setting the cut point to include all persons with the disease , many false positives will be introduced as persons without the disease have results above the cut point . Patients testing negative on
a sensitive test can be safely considered disease free , whereas patients who test positive should receive additional diagnostic evaluation or treatment. In this example , a bimodal distribution of patients with and without disease is presented . All patients without
disease are included in the area beneath the not-infected curve while all patients with disease are included in the area beneath the infected curve . There is overlap between the two , suggesting that some patients will test equivalently on the test but may or may
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not have the disease . Setting the cut point to point B would permit all patients within the area under the infected curve to be identified as positive, which maximizes sensitivity, while minimizing the number of false positives , and therefore optimizing specificity while
prioritizing sensitivity.
Incorrect Answers : A . C , D , and E.
Choice A would permit 10D% sensitivity, as all patients within the area under the infected curve would test positive , however, in comparison with point B (which also identifies all infected patients), point A would include a larger fraction of false positives. This would
reduce the specificity of the test without further increasing sensitivity, which would worsen its performance.
Choices C , D . and E all miss a substantial fraction of infected patients and wou d all have a sensitivity less than 100% , making them subopttmal for use in ruling out a significantly fatal disease .
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Educationa - Objective: The cut point of a test should be set to optimize sensitivity, specificity, or both depending on the clinica utility of the test . A sensitive test should be employed when ruling out a significantly mortal or morbid diagnosis .
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9 . A GG -year- old man with type 2 diabetes melfitus and hypertension is brought to the emergency department 30 minutes after the sudden onset of left eyelid drooping double vision, and mild weakness of the right hand and leg . His pulse is 88/min and regular
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and bkxxl pressure is 159/' 99 mm Hg . Examination of the head shows a substantially droopy left eyelid and in primary gaze: the left eye is exotropic and somewhat lower than the right. He has slowed finger movements on the right a pronator drift with the
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right hand and mild hyperreflexia on the right . Which of the following is the most likely site and diagnosis of the patient' s lesion?
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A ) Angular gyrus ( Gerstmann syndrome)

B ) Dorsolateral thalamus (Dejerine -Roussy syndrome)
C ) Lower medulla (Wallenberg syndrome)
D ) Lower midbrain (Weber syndrome )
E ) Upper spinal cord ( Homer syndrome )
This patient likely has a lesion of the lower midbrain that affects the cerebral peduncle and the oculomotor nerve, which causes contralateral hemiparesis and ipsilateral oculomotor palsy , known as Weber syndrome . The cerebral peduncle refers to the anterior
portion of the midbrain and includes the crus cerebri, which contains the corticospinal tract and is supplied by paramedian branches of the posterior cerebral artery. Upper motor neurons of the corticospinal tract originate in the primary motor cortex descend
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ipsilaterally through the internal capsule and midbrain (within the crus cerebri) , decussate in the caudal medulla and then descend contralateralty in the spinal cord to synapse with the contra ateral lower motor neuron . A brainstem lesion of the corticospinal tract
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leads to contralateral weakness in an upper motor neuron pattern of dysfunction (eg : spastic paralysis: pronator drift , and hyperreflexia). The oculomotor nerve (cranial nerve III ) is located anteriorly between the two cerebral peduncles and may also be affected by
strokes of the paramedian branches of the posterior cerebral artery leading to ipsilateral dysfunction of the extraocular muscles and consequent diplopia along with ptosis and a deficit in pupillary constriction . CVAs occur because of ischemic or hemorrhagic loss of
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blood supply to the brain. Approximately 80 -85% of CVAs are ischemic , commonly arising from thromboembolic disease (eg . middle cerebral artery occlusion from a thrombus ) , whereas 15- 20% of CVAs are hemorrhagic and caused by blood vessel rupture (eg ,
hypertension- related intraparenchymal hemorrhage from a perforating artery ). Risk factors for CVAs include smoking , hypertension, diabetes mellitus, carotid or intracranial atherosclerotic disease , history of hypercoagulability, atrial fibrillation , and advanced age.
Classically, CVAs manifest as a neurologic deficit related to the affected part of the brain.
Incorrect Answer : A, B. C . and E.
Patients with angular gyrus ( Choice A) damage may demonstrate agraphia , acalculia, finger agnosia , and left- right disorientation . This constellation of symptoms is known as Gerstmann syndrome .
The dorsolateral thalamus ( Choice B) connects with the limbic system and may mediate the emotional aspects of pain As such , lesions of this brain area may lead to post-stroke intractable pain , known as thalamic pain syndrome or Dejerine -Roussy syndrome .
Lesions of the lower medulla ( Choice C ) may affect the nuclei of multiple cranial nerves , the spinal trigeminal nucleus, solitary nucleus vestibular nuclei, and nucleus ambiguus ; the sympathetic , spinothalamic , and spinocerebellar tracts may also be affected .
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Consequently lesions of the lower medulla typically lead to ipsilateral facial numbness impaired taste sensation , vertigo with nystagmus dysphonla , dysarthria , dysphagia . Horner syndrome , pain and temperature sensation deficits in the contralateral arms and
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legs, and/or ipsilateral ataxia . This constellation of symptoms is known as Wallenberg syndrome.
Lesions of the upper spinal cord ( Choice E ) may interrupt the sympathetic nerve supply to the ipsilateral face and eye , which results in Horner syndrome . Horner syndrome classically presents with ipsilateral ptosis , miosis , and anhidrosis .
Educational Objective: In Weber syndrome , a stroke of the paramedian branches of the posterior cerebral artery affect the cerebral peduncle , containing the corticospinal tract and the neighboring oculomotor nerve . Patients typically present with ipsilateral
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oculomotor nerve palsy (diplopia , ptosis , primary gaze palsy, pupillary constriction deficits ) and contralateral hemiparesis with an upper motor neuron pattern of dysfunction.
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Exam Section 1: Item 10 ol 50 National Board of Medical Examiners^
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10 . A 12 -year- old boy is brought to the physician by his parents because of bed-wetting . He urinates 10 to 15 times each day. He says that he is constantly thirsty and drinks large quantities of liquid throughout the day. Urinalysis shows a specific gravity of
1.003. A 24 -hour urine collection shows a creatinine clearance of 140 mL/min, with a total urine volume of 7600 mL and urine osmolality of 230 mOsmol /kg H 20 . A tumor affecting which of the following hypothalamic nuclei is most likely involved in producing
this patient's symptoms ?
A ) Anterior
B ) Arcuate
C ) Dorsomedial
D ) Lateral
E ) Posterior
F ) Supraoptic
G ) Ventromedial
Correct Answer : F.
Central diabetes insipidus may result from a tumor involving the hypothalamic paraventricular and supraoptic nuclei and is characterized by the inadequate secretion of antidiuretic hormone (ADH , also known as vasopressin ) from the posterior pituitary. Normally,
increased plasma osmolality will be sensed by osmoreceptors and result in the increased production of vasopressin in the hypothalamic paraventricular and supraoptic nuclei . Vasopressin is subsequently released by the posterior pituitary gland . ADH binds V 2
receptors of the late distal convoluted tubule and the collecting duct principal cells , which results in the insertion of aquaporin channels in the lumina : surface and increases free water absorption. This process is typically utilized to maintain tight regulation of the
serum osmolality. Inadequate production of ADH by the hypothalamus and release by the posterior pituitary gland may occur in the setting of various pathologies , such as pituitary tumors , trauma , tuberculosis , or intracranial surgery. Inis results in a decreased
ability to absorb adequate amounts of free water within the collecting duct , which results in dilute urine and increased serum osmolality. Patients typically present with extreme thirst, production of large volumes of dilute urine, and altered mental status . Treatment
requires the administration of desmopressin , an analog of vasopressin (ADH) , which results in the reabsorption of free water via aquaporin insertion in the collecting duct .
Incorrect Answers : A, B . C . D , E . and G.
The anterior hypothalamic nucleus ( Choice A) is involved in thermoregulation , specifically in cooling.
The arcuate hypothalamic nucleus ( Choice B) contains complex regulatory functions that are involved in appetite stimulation .
The dorsomedial hypothalamic nucleus ( Choice C) is involved ; n the regulation of feeding and circadian rhythm.
The lateral hypothalamic nucleus ( Choice D) is important in promoting appetite under the stimulation of ghrelin.
The posterior hypothalamic nucleus ( Choice E ) is involved in thermoregulation specifically in heating .

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The ventromedial hypothalamic nucleus ( Choice G) is important in promoting satiety under the stimulation of leptin.
Educational Objective: Central diabetes insipidus may result from a tumor involving the hypothalamic paraventricular and supraoptic nuclei and is characterized by inadequate secretion of antidiuretic hormone. Lack of antidiuretic hormone leads to decreased free
water reabsorption from collecting ducts , resulting in an inability to concentrate urine and an abnorma ly increased serum osmolality.
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11 . A 2 G -year- old man comes to the physician because of fever cough, chest pain, and malaise for 2 weeks. He moved to central California 6 months ago. A complete blood count shows mild eosinophiilia . A chest x -ray
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shows patchy bronchopneumonia. Culture of the sputum grows a mold with the morphology shown in the photomicrographr with the arrow indicating the infectious particle . Which of the following is the most likely causal
organism?
A ) Actinomyces israelii
B ) Coccidioides immitis
C ) Histoplasma capsuiatum m
D ) Legionella pneumophila * n
E } Mycobacterium tuberculosis Ice
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F ) Nocardta brastliensis
> OM I
G ) Staphylococcus aureus
H ) Streptococcus pneumoniae
Coccidioicies immitis is an endemic fungus of the Southwestern United States and central valley of California that typically causes coccidioidomycosis , a self-limited respiratory illness. Signs and symptoms include fever fatigue , cough : arthralgia , and myalgia.
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Patients may also present with erythema nodosum . Coccidioidomycosis can potentially present with disseminated disease , especially in immunocompromised patients , and cause infections of the skin, bone , and central nervous system. Silver stain of sputum or
tissue biopsy demonstrates large spherules containing endospores. Diagnosis can be facilitated with enzyme- linked immunosorbent assay (ELISA ) testing and be confirmed with polymerase chain reaction. Treatment is with oral or intravenous antifungals ,
including agents from the azole or polyene classes.
Incorrect Answers : A, C , D , E, F, G, and H .
Actinomyces israelii ( Choice A ) is a Gram-positive , anaerobic bacillus that forms branching filaments and yellow granules it typically causes abscesses of the head and neck, often with draining fistulous tracts.
,
Histoplasma capsuiatum (Choice C) is a fungus native to the Ohio river and Mississippi river valleys that can cause pneumonia and is spread by the droppings of birds or bats . It is identifiable as oval yeasts within macrophages .
Legioneiia pneumophila ( Choice D) is a Gram-negative bacillus that is transmitted primarily through aeroso: s from water sources . It causes Legionnaire disease, characterized by fever, pneumonia , and gastrointestinal symptoms. It can be identified by positive
staining with silver stains and its fastidious nature , requiring culture on charcoal yeast extract with supplemental iron and cysteine .
Mycobacterium tuberculosis (Choice E) is an acid -fast bacillus that causes tuberculosis. It is identifiable by its thick , waxy capsule , positive acid - fast staining, and by the presence of caseating granulomas with multinucleated giant celts.
Nocardia brasiiiensis ( Choice F) is a Gram-positive, aerobic acid fast bacillus that forms branching filaments it can cause pneumonia, as well as cutaneous and central nervous system infections in immunocompromised patients .
, ,
Staphylococcus aureus ( Choice G) is a Gram -positive coccus that is a common cause of skin and soft tissue infections in adults it is identifiable as Gram - positive cocci in clusters .
,
Streptococcus pneumonip ( Choice H ) is a Gram-positive dipiococcus that is a common cause of community- acquired pneumonia infections in adults. It is identifiable as Gram - positive cocci in chains or pairs .
Educational Objective : Coccidiomycosis is a fungal infection endemic to the Southwestern United States and to the central valley of California fhat typically presents as a self -limited respiratory illness. Signs and symptoms typically include fever, fatigue cough
,
arthralgia , and myalgia . Disseminated disease is possible , especially irt immunocompromised patients.
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12 . An investigator is conducting a study of the effects of a newly discovered spider venom on neuromuscular transmission . An isolated nerve muscle preparation is bathed in a solution containing the venom ; there is a decrease in the end-pEate potential
amplitude following stimulation of the nerve . The presence of the venom does not change the amplitude of the nerve action potential or the muscle potential change in response to the exogenous application of acetylcholine to the neuromuscular junction .
Blockade of which of the following by the venom best explains the decreased end-plate potential amplitude in this study?
A ) Chloride conductance in the nerve terminal

B ) Function of acetylcholinesterase
C ) inactivation of voftage-gafed sodium channels in the muscle
D ) Insertion of acetyEcholine receptors into the muscle membrane
E ) Presynaptic , voltage -gated calcium channels
Correct Answer : E
The blockade of presynaptic , voltage- gated calcium channels would lead to decreased end-plate potential amplitude . Normally action potentials lead to depolarization in the terminal bouton of the axon. Presynaptic voltage-gated calcium channels consequently
,
open and allow calcium influx , which triggers the exocytosis of acetylcholine- filled vesicles into the synaptic cleft . Acetylcholine diffuses across the synaptic cleft and binds nicotinic acetylcholine receptors (NAChRs } on the skeletal muscle ceil membrane. The bound
NAChRs aliowf sodium influx ( and a lesser degree of potassium efflux) , leading to depolarization of the postsynaptic membrane potential . Once the threshold membrane potential is reached , voltage -gated sodium channels open and the depolarization propagates
down the postsynaptic membrane, representing the muscle action potential Each NAChR is associated with its own end-plate potential, or voltage change, that results from the binding of acetylcholine. The summation of the end-pEate potentials represents the
membrane potential . Decreased synaptic acetylcholine concentrations result in decreased end - plate potential amplitudes.
Incorrect Answers : A, 6 , C, and D.
Blockade of chloride conductance in the nerve terminal ( Choice A) would iead to decreased chloride influx and a more positive presynaptic membrane potential . Consequently more voltage-gated calcium channels would open , leading to calcium influx and
,
increased release of acetylcholine vesicles. The amplitude of end-plate potentials would increase .
Blockade of the function of acetylcholinesterase ( Choice B) leads to decreased degradation of synaptic acetylcholine and is the mechanism of medications (eg . pyridostigmine ) utilized for myasthenia gravis . An increased synaptic acetylcholine concentration would
increase the amplitude of end-plate potentials .
Blockade of the inactivation of voltage- gated sodium channels in the muscle (Choice C ) would not affect end-plate potential amplitudes , which are instead influenced by synaptic acetylcholine concentrations . Blockade of sodium channel inactivation would result in
an increased amplitude of muscle action potentials.
Blockade of the insertion of acetylcholine receptors into the muscle membrane ( Choice D) would not decrease the end -plate potential amplitude , which is instead influenced by synaptic acetylcholine concentration . Fewer acetylcholine receptors would lead to a
decreased muscle membrane potential.
Educational Objective: When acetylcholine binds postsynaptic nicotinic acetylcholine receptors , each receptor causes Its own postsynaptic voltage change which is called an end-plate potential. The summation of the end - plate potentials represents the membrane
,
potential. The synaptic acetylcholine concentration influences the amplitude of end - plate potentials .
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13. A 38 -year- old woman with asthma comes to the physician for advice concerning contraception . She is sexually active with one partner and they use condoms inconsistently. Current medications include inhalational fluticasone and albuterol . She has
smoked one - half pack of cigarettes daily for 20 years and drinks two alcoholic beverages daily. She does not use illicit drugs. Her maternal grandmother developed breast cancer at the age of 5 S years . She is 157 cm ( 5 ft 2 in) tall and weighs 82 kg (180 lb ) :
BMI is 33 kg/ m 2. Her vital signs are within normal limits. Physical examination shows no other abnormalities . This patient should be advised to avoid the use of an oral contraceptive because of which of the following historical factors?
A ) Age
B ) Alcohol use
C ) Asthma
D ) Family history
E ) Obesity
F ) Tobacco use
Correct Answer: F.
Combined oral contraceptive pills ( OCRs) contain a combination of estrogen and progesterone . They are primarily used for contraceptive purposes but can also be used in a variety of gynecologic disorder such as polycystic ovarian syndrome (PCGS ) r
menorrhagia , and endometriosis . A sustained release of progestin and estrogen prevents ovulation and causes thickening of the cervical mucus along with thinning of the endometrial layer by inhibiting the release of gonadotropin-releasing hormone follicle -
,
stimulating hormone , and luteinizing hormone . OCRs are typically administered as a daily pill for three weeks , followed by a daily placebo pill for one week during which time withdrawal bleeding occurs. They are associated with increased hypercoagulability and are
,
therefore contraindicated in patients with a history of deep venous thrombosis pulmonary embolism , stroke , or myocardial infarction . They are also contraindicated in patients who are 35 years of age or older and concomitantly smoke 15 or more cigarettes per day,
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along with patients diagnosed with hypertension , migraine with aura, severe cirrhosis , and breast cancer. Common adverse effects include nausea , breast tenderness , irregular menstrual periods , and a mildly delayed return to fertility following cessation. OCRs are
contraindicated in this patient caused by her tobacco use .
Incorrect Answers : A . B C . D, and E

(
:
Age ( Choice A ) can increase the risks associated with OCRs, as there is an increased baseline risk for cardiovascular disease. However, this patient is only 38 years old , and age a one is not a contraindication to OCR use without smoking history
Alcohol use ( Choice B ) can preclude the use of OCRs if severe and associated with consequent cirrhosis , as they are generally contraindicated in severe decompensated cirrhosis However, alcohol use a. one would not be an indication to avoid OCRs .
Asthma (Choice C) commonly presents with shortness of breath, prolonged cough, and bronchospasm. OCRs do not cause alterations in respiratory mechanics and are not contraindicated in asthmatic patients .
Family history of breast cancer ( Choice D) could raise concern for the use of estrogen- containing oral contraceptives , as a strong family history of breast cancer could indicate a possible BRCA 1 or 2 mutation that would increase the patient ' s risk for developing
breast cancer in the setting of exogenous estrogen administration. However, this patient's grandmother developed breast cancer at 58 , making a BRCA 1 or 2 mutation unlikely.
Obesity (Choice E) independently increases the risk for cardiovascular disease, stroke , and thromboembolism When administered to an obese patient , OCRs do increase the relative risk for thromboembolism . However, the absolute risk is less than the risk for
thrombosis in an active smoker taking oral contraceptive pills.
Educational Objective: Combined oral contraceptive pills contain estrogen and progesterone to promote anovulation and prevent pregnancy as well as to treat PCOS , menorrhagia , and endometriosis. They should be avoided in patients with a history of deep
,
venous thrombosis , pulmonary embolism , stroke , myocardial infarction, hypertension, migraine with aura , severe cirrhosis and current breast cancer . They are also contraindicated in patients 35 years or older who concomitantly smoke cigarettes .
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14 . A 27-year- old man with AIDS comes to the physician because of a 6 - week history of progressive memory loss imbalance , clumsiness , and difficulty finding words. The symptoms began with an inability to
,
concentrate 3 months ago . He is not adherent to combination antiretroviral therapy and recently recovered from Pneumocystis jirovecii (formerly P. carinii ) pneumonia . An MRI shows diffuse, poorly defined ,
bilateral hyperintensities within cerebral white matter. A stereotactic biopsy specimen shown in the photomicrograph depicts cells scattered predominantly along the perivascular spaces. Which of the following is
the most likely diagnosis?
A ) Cryptosporidiosis
B ) HIV encephalopathy
C ) HIV protease inhibitor toxicity
D ) Lymphoma
E ) R jirovecii infection
HIV encephalopathy is the most likely diagnosis in this patient with AIDS, progressive memory loss , and motor deficits who does not adhere to antiretroviral therapy. HIV encephalopathy is a diagnosis of exclusion in patients with HIV and other causes of
encephalopathy such as toxoplasmosis , meningitis , encephalitis, bacterial abscess , progressive multifocal leukoencephalopathy (PML ) , or primary centra - nervous system ( CHS) lymphoma should be ruled out . The classic triad of HIV encephalopathy involves
movement disorders , psychomotor impairment , and memory deficits . While it can occasionally be confused with PML patients with PML tend to have a more rapid disease progression , focal deficits and different findings on MRI . In HIV encephalopathy, the MRI
,
demonstrates multi pie. symmetric , and poorly demarcated T2 hyperintense lesions scattered in the subcortical white matter. Brain biopsy characteristically demonstrates microglial nodules with multinudeated giant cells as in this case .
Incorrect Answers : A, C , D , and E.
Cryptosporidiosis ( Choice A ) is caused by Cryptosporidium parvum that presents with severe diarrhea in patients with AIDS. Symptoms include fever, weight loss , symptoms of dehydration and onhostasis , severe , watery diarrhea, cramping abdominal pain
nausea, and vomiting . Disseminated infection can involve the lungs and liver but encephalopathy or encephalitis does not occur .
HIV protease inhibitor toxicity (Choice C) can present acutely with nausea and vomiting , but long-term complications commonly include lipodystrophy and increased cardiovascular risk . They do not cause encephalopathy.
Lymphoma ( Choice D ) in patients with AIDS can take on many forms, but primary CNS lymphoma is common . It often presents with seizures , lethargy, subacute memory loss , and headache. Physical examination may show neurologic deficits stemming from
structural disruption caused by the location of the mass. MRI will usually show a dominant cortical mass. Multiple lesions distributed throughout the cortex would be atypical .
P. jirovecii ( Choice E ) is an opportunistic yeast-iike fungal organism that can cause pneumonia in immunocompromised patients . Chest imaging typically shows diffuse , bilateral infiltrates , often prominently about the hila . Methenamine silver or toluidine blue
,
selectively stain the cyst walls and are used to confirm the diagnosis .
Educational Objective: HIV encephalopathy is typica ly a diagnosis of exclusion. Patients commonly present with subacute to chronic memory and language impairment and psychomotor deficits . MRI shows symmetrically distributed , poorly defined , T2
hyperintense lesions in the subcortical white matter . Brain biopsy shows multinudeated giant ceils and microgliai nodules.
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15. A 4 -year- old boy has had a viral upper respiratory tract infection for the past 3 days . Clearance of the virus is most dependent on which of the following?
A ) Activation of macrophages
B ) Class I MHC - viral peptide complex presentation
C ) Class II MHC-viraj peptide complex presentation
D } Phagocytosis of viral particles by CD 3+ T lymphocytes
E ) Production of memory 6 lymphocytes
F ) Proliferation of memory T lymphocytes
G ) Proliferation of plasma cells
Class I MHC -virai peptide complex presentation with subsequent activation of CDS+ T lymphocytes wiJI most likely contribute to clearance of the virus. Viruses are obligate intracellular pathogens and must enter a cell] to proliferate. Viral particles that are released
from infected cells are taken up by professional antigen presenting cells ( APCs) such as dendritic cells . These large proteins are shuttled to the proteasome, which generates smaller fragments of protein that are in turn shuttled to the endoplasmic reticulum (ER ). In
the ER , these peptides are attached to class f MHC molecules before being transferred to the Golgi apparatus and then to the cytoplasmic membrane where they are expressed . Viral particles may also be presented on class I MHC molecules on the surface of
infected cel!s: although these cells often iack the costimulatory capabitities of APCs . CD 8+ T lymphocytes possess unique T-celP receptors (TCRs) that recognize particular viral antigens and binding of the ICR to the class I MHC- antigen complex activates the
,
CD8 + T lymphocytes. In turn they release cytokines such as interferon- y and tumor necrosis factor they also interact with cell surface Fas and FasL to induce apoptosis of infected cells. They can release granzyme and perforim which cause membrane pore
'
formation and Jead to apoptosis of infected cells .
Incorrect Answers : A . C D E : F: and G .

; ;
Activation of macrophages ( Choice A ) occurs primarily through IL -12/IFN-y signaling . Activated macrophages can become histiocytes and may form granulomas in the case of some infections (eg Mycobacterium tuberculosis}
; .
Class II MHC-viral peptide complex presentation ( Choice C) activates CD 4+ T lymphocytes which assist B lymphocytes in making antibodies : and recruit macrophages . CD8+ T lymphocytes, and leukocytes to the site of activation . While they do contribute to viral
clearance they are incapable of directly killing infected cells , unlike Class I MHC- CD8+ T lymphocyte interactions.
,
Phagocytosis of viral particles by CD 8+ T ymphocytes ( Choice D) is incorrect. Viral particles are phagocytosed by APCs and their peptide fragments are presented via class II MHC molecules on the celi surface .
Production of memory B lymphocytes ( Choice E) occurs during the course of a viral infection after B lymphocytes class switch and differentiate into plasma cells ( Choice G), which secrete large quantities of immunoglobulin . While a critical part of humoral immunity,
the production of specific antibodies takes time and does not contribute to early clearance of a virus unless specific memory B lymphocytes and plasma cells already exist.
Proliferation of memory T lymphocytes (Choice F) is a feature of viral infections although it occurs later in the course and does not contribute to early viral clearance upon initial infection unless the patient is re- exposed to the same virus . Memory T lymphocytes
,
reside in peripheral tissues ; upon re- exposure rapidly differentiate into effector cells such as CD8+ T lymphocytes.
Educational Objective: Early vira: clearance is predicated upon the actions of cytotoxic CD 8+ T lymphocytes , which recognize viral antigen complexed to class l MHC molecules presented on the surface of APCs and virally infected cells. Binding results in T
lymphocyte activation with the subsequent release of inflammatory cytokines to attract other immune cells , release of granzyme and perforin to form membrane pores in infected ceils : and initiation of apoptosis in infected cells.
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16. The graph shows diastolic and end-systolic relationships of the left ventricle. The solid line shows the control pressure - volume loop in a single cardiac cycle . If a healthy person is given nitroprusside and reflex responses are blocked which of the following
,
labeled end-systolic pressure points is most likely?
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Correct Answer D .
Nitroprusside is an intravenous , titratable vasodilator that can be used for the treatment of hypertensive emergencies. It breaks down in circulation to release nitric oxide: which in turn activates guanylate cyclase in vascular smooth muscle to result in vascular
smooth muscle relaxation and vasodilation via a cyclic GMP pathway. It typically induces a reflex tachycardia . Sodium nitroprusside preferentially dilates arterial vessels over venous vessels , resulting in a decrease in afterload without significant change in
preload . An isolated decrease in afterload results in a shortened pressure- volume loop ( less left ventricular pressure is needed to open the aortic valve ) and a decreased end-systolic left ventricular volume (because of an increased stroke volume and ejection
fraction) . The associated end -systolic pressure point on this graph is represented by point D .
Incorrect Answers : A . B. C . and E.
Choice A represents a point that may be observed if afterload is increased and cardiac contractility is increased . The left ventricular pressure needed to open the aortic valve is increased , and the increased contractility maintains the stroke volume to result in the
same end-systolic left ventricular volume as the control.
Choice B represents the end-systolic pressure point associated with an isolated increase in afterload. The left ventricular pressure needed to open the aortic valve is increased and the stroke volume is reduced resulting in an increased end-systolic left ventricular
:
volume.
Choice C represents an end -systolic pressure point that may be seen in the case of decreased afterload and decreased cardiac contractility, with reduced end-systolic left ventricular pressure and a reduced stroke volume resulting in increased end -systolic left
ventricular volume .
Choice E represents a point that may occur with an isolated increase in cardiac contractility. The afterload and end-systolic left ventricular pressure remain the same and an increase in stroke volume results in a lower end-systolic left ventricular volume .
,
Educational Objective: Pressure-volume loops provide information about cardiac mechanics . The shape and position of the loop is dependent on preload , afterload, and cardiac contractility. A decrease in afterload results in a shorter loop that is shifted to the left ,
as lower ventricular pressure is needed to open the aortic valve and a greater volume of blood is ejected .
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17 . The patient whose cardiac function is Illustrated most likely has which of the following?
z> n Normal
A } Arteriovenous malformation CL
B ) Cardiac tamponade o
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C ) Congestive heart failure CO
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D ) Cor puEmonale CB
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E ) Restrictive cardiomyopathy
Left ventricular end- diastolic

volume
Correct Answer : C .
The Frank-Starling mechanism describes the phenomena by which cardiac output is dependent on the amount of cardiomyocyte fiber stretch prior to contraction as represented by the left ventricular end -diastolic volume . A greater pre -contraction stretch results in
,
a greater force of contraction (to a point ) : and the relationship is demonstrated by Frank-StarEing curves. A given Frank -Starling curve applies for constant afterload and inofropy. Changes in afterload and/or inotropy shift the curve up or down . This patient has a
Frank- Starling curve that is shifted down : indicating that for a given preload , there is reduced cardiac output relative to normal. This may occur in decreased inotropic states such as congestive heart failure with the administration of negative inofropes: or in the
,
setting of increased afterload . The curve shifts up in positive inotropic states and/ or with decreased afterload .
Incorrect Answers : A, B : D, and E.
Arteriovenous malformation ( Choice A ) results in low-resistance , high - volume flow of blood from the arterial to the venous system with greatly increased venous return . The increase in preload causes a greater distension in the cardiomyocyte fibers at the end of
diastole , which results in increased cardiac output per the Frank-Starling relationship.
Cardiac tamponade ( Choice B ) result in decreased ventricular filling because of compression of the heart by fluid in the pericardium. In the absence of other factors affecting afterload or cardiac contractility the Frank- Starling curve would not be depressed.
,
Cor pulmonale ( Choice D) describes right ventricular failure resulting from chronic pulmonary hypertension Left ventricular contractility and afterload are not affected , and the Frank- Starling curve for the left ventricle would not shift .
Restrictive cardiomyopathy ( Choice E) results in decreased compliance of the ventricular wall, with diastolic dysfunction and preserved left ventricular systolic function .
Educational Objective: The Frank - Starling mechanism describes the relationship between cardiac output and left ventricular end-diastolic volume (preload ) . Cardiac output can be described by a family of curves that shift depending on afterload and cardiac
contractility.
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18. A 28 -year- old woman has had fatigue and heavy menstrual periods during the past year . She is a vegetarian who eats eggs and dairy products. Her diet contains littfe fruit . Which of the following erythrocyte types is most likely to be present on a peripheral
blood smear from this patient?
A ) Macrocytes
B ) Microcytes
C ) Ovalocytes
D ) Spherocytes
E ) Stippled cells
Microcytes are most likely to be present in this patients periphera blood smear which is suggestive of iron deficiency anemia (IDA) in the setting of heavy menstrual periods and low dietary iron intake (vegetarianism) . Erythrocytes in the setting of IDA are pale
(hypochromic) and small in size (microcytic) but normal in shape . Iron is required for the synthesis of heme , which is a necessary component of the hemoglobin molecule , and thus , of erythrocytes. It functions to shuttle oxygen to and from peripheral tissues in ,
individuals who do not have an adequate intake of dietary iron in the form of heme obtained from animal meat , especially when other causes of ongoing blood loss such as heavy menstruation are present deficiency can develop . IDA may also develop as the result
,
of chronic blood loss from colorectal bleeding , as a result of malabsorption syndromes (eg , celiac disease ) and in patients who have undergone gastric bypass surgery. Erythrocytes on the peripheral blood smear are hypochromic and microcytic as a result of
,
deficient hemoglobin concentration. It is hypothesized that erythrocytes are microcytic as a result of continuing erythrocyte division in order to reach an adequate hemoglobin concentration ; because hemoglobin stores are inadequate , cell division continues beyond
what would normally occur and causes the cells to be smaller than normal. Treatment for this patient would include management of her menstrual bleeding and oral iron supplementation.
Macrocytes ( Choice A ) refer to larger than normal erythrocytes and are seen in the setting of folate or vitamin B 12 deficiency. This patient has chronic blood loss most likely leading to iron deficiency and is likely to have adequate stores of folate and vitamin 612,
which are consumed in high amounts in most vegetarian diets.
Ovalocytes ( Choice C) are oval shaped erythrocytes also known as elliptocytes . While they can be seen in IDA , they are more commonly seen in conditions such as myelofibrosis thalassemia megaloblastic anemia , and myelodysplastic syndrome.
, ,
Spherocytes ( Choice D) are small, dark , round cells with a high concentration of hemoglobin that are most commonly seen in hereditary spherocytosis or in cases of autoimmune hemolytic anemia . They are not seen in IDA.
Stippled cells (Choice E) suggest the presence of precipitated ribosomes and ribosomal RMA within an erythrocyte. Classically , coarse basoph: ic stippling is associated with lead poisoning.
Educational Objective : Patients who follow a strict vegetarian diet and have clinically significant blood loss from menstruation are at risk far iron deficiency anemia as iron is required for the normal synthesis of heme . IDA presents with hypochromic , microcytic
erythrocytes on peripheral blood smear. Treatment includes control of the underlying bleeding and oral iron supplementation .
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19. A 13 -year-old girl is brought to the physician by her mother because of a mass in her armpit for 3 days. She has a history of several similar masses since early childhood that have resolved with treatment. She also
has had several episodes of pneumonia rhinitis and perianal abscesses since birth . Her temperature is 37 X ( 9 S. 6 aF). Physical examination shows a 2 -cm . raised red . tender fluctuant mass in the right axilla .
, , ,
There is mild hepatosplenomegaly. A complete blood count shows a mildly increased leukocyte count. A chest x -ray shows bilateral interstitial infiltrates . A photomicrograph of lung tissue obtained on biopsy is
shown . A nitroblue tetrazolium test shows deficient reduction by granulocytes. The axillary mass is incised and drained and culture of the fluid grows Staphylococcus aureus . Which of the following is the most likely
diagnosis?
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Chronic granulomatous disease ( CGD ) is the most likely diagnosis in this patient with a Staphylococcus aureus abscess : history of prior similar infections and an abnormal nitroblue tetrazolium test . CGD is defined by deficiency of the NADPH oxidase complex ,
,
which is essential for normal neutrophil intracellular killing of pathogens. NADPH oxidase uses oxygen as a substrate for the generation of free radicals (superoxide anions). Free radical oxygen species are subsequently used for the creation of hydrogen peroxide
and hypochlorous acid . Activation of thrs pathway leads to the respiratory burst which results in bacterial death Deficiency of NADPH oxidase renders phagocytes incapable of neutralizing catalase-positive bacteria which are capable of neutralizing their own
,
hydrogen peroxide : thus leaving the host cells without the substrate necessary to complete the respiratory burst . Diagnosis is made by an abnormal dihydrorhodamine test or a nitroblue tetrazolium reduction test . Jn this latter test , normal phagocytes use the action
of NADPH to reduce nitroblue . which leads to a color change from yellow to blue. Patients with CGD will not demonstrate color change . Recurrent pneumonia is the most common presenting infection in patients with CGD: and the most common infecting bacteria
include Staphylococcus species , Aspergillus species, Burkholcieria cepacia , and Nocardia species. Patients with CGD are also at risk for fungal infections , especially Aspergillus species .
Incorrect Answers : A , C D . and E.

;
presentingGhediak -Higashi syndrome ( Choice A ) is a rare , autosomal recessive disorder of the immune system caused by mutations in the lysosomal trafficking regulator gene (LYST ) that encodes a protein essential for normal formation and transportation of
lysosomes within the cell . The clinical manifestations include frequent bacteria! infections , oculocutaneous albinism , peripheral neuropathy, and progressive neurologic dysfunction.
Myeloperoxidase deficiency ( Choice C ) is a common inherited immunodeficiency syndrome characterized by the inability to produce hypoch orous acid within phagolysosomes. Disease is typically mild and may present with recurrent Candida albicans infection.
Neutrophil -specific granule deficiency ( Choice D) results from defective production of granules within neutrophils . The disorder is characterized by recurrent pyogenic infections that occur early in childhood as well as impaired production of defensins . Patients
have a normal nitroblue tetrazolium test .
Wiskott-Aldrich syndrome ( Choice E) is caused by a mutation in the WAS gene on the X-chromosome that encodes a protein essential for the actin cytoskeleton rearrangement that occurs during interactions between T lymphocytes, antigen-presenting cells and ,
B lymphocytes : this can lead to an impaired innate and adaptive immune system . The phenotype is variable but classically includes eczema , thrombocytopenia , and infections with encapsulated bacteria and opportunistic pathogens.
Educational Objective : CGD is caused by NADPH oxidase deficiency and results in impaired ;: ntraceliu! ar killing of pathogens. This presents as recurrent pyogenic infections with catalase -positive organisms such as S. aureus with norma! concentrations of
leukocytes and immunoglobulins.
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20 . A G 7 -year- old white woman undergoes punch biopsy of an urticarial lesion on her back . When the biopsy specimen container is received in the laboratory, it is determined that it contains two specimens instead of one . Review of the additional specimens
received from the physician ' s office indicates that specimens from two separate patients were inadvertently shipped in the same container. The other specimen is from the back of a dark-skinned . 55-year -old Nigerian woman. An increase in which of the
following in the specimen from the Nigerian patient is most likely to differentiate these two specimens ?
A ) Number of melanocytes
B ) Number of melanophages
C ) Number of melanosomes
D ) Size of melanocytes
Melanin is a pigment made within a specialized cellular organelle called a melanosome found in melanocytes , which are dendritic cell derivatives that reside in the basal layer of the epidermis. Melanocytes are derived from neural crest cells, which originate at the
dorsal neural tube . During embryologic development , they migrate from dorsal to ventral, and then to the epidermis . Tne initial substrate in the creation of melanin is the amino acid tyrosine . After producing melanin from tyrosine the melanosomes are transferred to
,
the surrounding keratinocytes . The variation in skin tones seen in different ethnic groups is based on the number of the melanosomes and the distribution of melanin within them in the keratinocytes not the number of melanocytes themselves. In patients with darker
skin, the melanosomes are more numerous and more densely packed with melanin . In patients with tighter skin, the melanin is distributed with less density, and there are fewer melanosomes. Melanin production is regulated in part by melanocyte- stimulating
hormone ( MSH ). MSH is a byproduct of proopiomelanocortin (POMC ) which also produces adrenocorticotropic hormone ( ACTH ). In adrenal insufficiency, stimulation ofACTH production by POMC simultaneously produces MSH . leading to diffuse hyperpigmentation
in affected patients .
Incorrect Answers : A . B , and D .
Neither the number of melanocytes ( Choice A } nor their size (Choice D) differs between patients with different skin types . Increased number, size , and nuclear/cytoplasmic ratio of melanocytes would be seen n melanoma a neoplasm of melanocytes . Lesions
,
concerning for melanoma are characterized clinically by asymmetry, irregular -appearing borders , variable coloration , a diameter greater than 6 mm, and rapid evolution in characteristics.
Melanophages are macrophages which have taker up melanin and reside in the dermis . Increased number of melanophages ( Choice Bj would not distinguish two patients with different skin types from each other . Melanophages are not routinely present in healthy
skin; rather , they develop when an inflammatory process has destroyed the basal layer of the epidermis , causing melanocytes and keratinocytes to release melanin.
Educational Objective : Melanin is a pigment made by melanocytes within a specialized cellular organelle called a melanosome . The number of melanosomes and density of melanin are what provide variation in skin tone .
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21 . An investigator is studying the adverse effects of a proteasome inhibitor bortezomib , on immune responses . Bortezomib is administered to a group of patients with relapsed multiple myeloma, and immune responses are observed. Which of the following
immunofogic processes is primarily affected by this drug?
A ) Activation of the complement cascade

B ) Activation of perforin
C ) Presentation of antigens to GD 8+ T lymphocytes
D } Secretion of histamine by mast ceils
E ) Secretion of interleukin-1 (IL-1J by macrophages
Presentation of antigens to CD 8+ T lymphocytes would be affected by the use of the proteasome inhibitor bortezomib . Proteasomes are large proteases with numerous domains that are present in both the cytoplasm and the nucleus . They are made of a and p
subunits and have an extensive role in cell cycle regulation but also in immune function The caspase . chymotrypsln , and trypsin-like protease capabilities of this enzyme complex are also critical to their role as antigen processing centers ; intracellular peptides are
,
processed in the proteasome for presentation on class I major histocompatibility complex (MHC). Antigen-bound class I MHC molecules are recognized by cytotoxic CDS+ T lymphocytes , so proteasome inhibitors blunt the response of CD 8+ T lymphocytes by
altering antigen presentation on the surface of MHC I molecules.
Incorrect Answers : A . 6 : D . and E.
Activation of the complement cascade ( Choice A ) is not a feature of proteasome inhibitors . The complement cascade is activated by the classical, alternative , or lectin pathways . Activation leads to opsonization of invading microbes direct microbial killing via
,
formation of the membrane attack complex (MAC ) , and proinfiammatory signaling (eg , C5a mediation of neutrophil chemotaxis).
Activation of perforin ( Choice B) occurs as a result of activated natural killer ceils, which are immune cells that primarily respond to an absence of MHC I molecules on the surface of cells. Perforins , along with granzyme , are proapoptotic agents and induce cellular
death . Proteasome inhibitors interfere with antigen presentation on MHC I molecules but do not affect the presence of MHC I molecules.
Secretion of histamine by mast cells (Choice D) occurs as a result of mast ceil degranulation, a process that primarily occurs during allergic reactions but can also occur in the setting of mast cell activation syndrome . This is not affected by proteasome inhibitors .
Secretion of interleukin-1 ( IL -1) by macrophages ( Choice E) has numerous effects , including the promotion of fever, vasodilation , and stimulation of endothelial ceils to express adhesion proteins for leukocyte recruitment . Secretion is not affected by proteasome
inhibitors .
Educational Objective : Proteasome inhibitors prevent antigen processing and presentation on class i MHC molecules , thereby blunting CD 8+ cytotoxic T lymphocyte activation. While this is an effective strategy to treat multiple myeloma it also makes patients more
,
prone to infections, especially viral infections.
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22 . A 3-month-old girl is brought to the physician 2 days after the mother felt masses in the infant ' s groin while bathing her Physical examination shows bilateral inguinal hernias and a shallow vagina that ends blindly. Serum studies show increased
concentrations of luteinizing hormone follicle- stimulating hormone, testosterone and dihydrotestosterone. During repair of the hernias gonads are found . A biopsy specimen of the gonads shows bilateral testes . The karyotype is 46 XY. Ultrasonography
: , ,
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shows no uterus or fallopian tubes. Which of the following is the most likely cause of the findings in this patient?
A ) Decreased 21-hydroxylase activity

B ) Decreased 5 o -reductase activity
C ) Defective androgen receptor
D ) Failure of testis to secrete anti-mullerian hormone
E ) Mutation of the sex-determining region Y gene ( SRY)
Androgen insensitivity syndrome is caused by a defect in the androgen receptor complex resulting in a genotypic XY male to develop external female or ambiguous genitalia and female secondary sexual characteristics . Testes are present and produce testosterone
normally: but absence of a functioning androgen receptor prevents hormone binding and thereby prevents the development of male sexual characteristics . Patients present with female external genitalia , scant pubic and axillary hair absent uterus and fallopian
,
tubes and a rudimentary vagina . Results of laboratory studies show increased concentrations of testosterone, estrogen , and luteinizing hormone. Menses wi i not occur because of the lack of cycled progesterone and estrogen , and the lack of a functional uterus
;
with endometrial lining .
Incorrect Answers : A . B : D , and E.
Decreased 21-hydroxylase activity ( Choice A) occurs in the setting of congenital adrenal hyperplasia, of which the most common form is 21-hydroxylase deficiency. Lack of this enzyme prevents production of aldosterone and cortisol . and results in excessive
androgen production . Genetically female patients present with hypoaldosteronism as well as virilization during infancy and genetically male patients present with precocious puberty in childhood .
,
Decreased 5 a -reductase activity ( Choice B) results in the insufficient conversion of testosterone to dihydrotestosterone (DHT ), leading to decreased concentrations of DHT and impaired virilization of the male urogenital tract . Individuals with 5 a -reductase deficiency
exhibit either female or ambiguous external genitalia , although demonstrate normal male internal genitalia because of normal concentrations of testosterone . Increased concentrations of DHT. as in this infant would not be found .
Failure of testis to secrete anti-mullerian hormone (Choice D) results in failure of suppression of the development of the paramesonephric (Mullerian) duct . Patients with an XY karyotype appear externally ma = e but have undescended testes and an incompletely
developed uterus.
Mutation of the sex-determining region Y gene ( SRY) ( Choice E) would cause an XY male to develop as a phenotypic female since the non-functional gene would result in the development of ovaries from the undifferentiated gonads , not testes. This would then
consequently result in the development of both normal internal and external female genitalia .
Educational Objective : Androgen insensitivity syndrome occurs because of a defect in the androgen receptor, and results in an XY genotypic male developing external female or ambiguous genitalia and female secondary sexual characteristics .
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23. A 35 -year- old man comes to the physician because of a 3-year history of an enlarging nose, coarsening of his facial features muscle weakness , and increased hand and foot size. Physical examination shows a large fleshy nose and prognathism . Fasting
serum studies show increased insulin-Jike growth factor - l , glucose , and triglyceride concentrations . Increased serum growth hormone concentrations do not decrease after the administration of oral glucose . Compared with a healthy patient , which of the
following best describes the metabolic changes in this patient?
Muscle Glucose Adipose Hepatic

Uptake Lipolysis Gluconeogenesis
A) T T
B) T l
C) T i
D) I T T
E) i T
F) I i i
Correct Answer : D
Acromegaly is caused by a growth hormone (GH) secreting pituitary adenoma that stimulates the excessive production of insulin-hke growth factor - 1 (IGF -1) by the liver. IGF -1 interacts with its receptor, a tyrosine kinase -based receptor that stimulates celE growth ,
proliferation and growth of the axial and appendicular skeleton . Acromegaly occurs after the closure of growth plates , and in this context excessive IGF -1 leads to expansion of flat bones and tissues. Excessive GH and IGF-1 leads to deranged glucose
,
homeostasis by increasing peripheral insulin resistance , impairing muscle and adipose uptake of glucose, increasing adipose lipolysis . and increasing hepatic gluconeogenesis . Consequently, up to half of patients with acromegaly develop diabetes mellitus.
Patients with acromegaly also exhibit increased rates of hypertriglyceridemia .
Incorrect Answers : A, B. C, E. and F.
Choices A , B , and C reflect states of increased muscle glucose uptake , which would occur in the setting of increased peripheral insulin concentrations or receptor sensitivity. Excessive concentrations of GH and IGF -1 lead to reduced peripheral insulin sensitivity.
Choices B . C , and F reflect states of decreased lipolysis . whereas deficient insulin signaling will lead to increased lipolysis .
Choices C . E, and F reflect states of decreased hepatic gluconeogenesis . GH directly stimulates gluconeogenesis , which is increased in acromegaly.
Educational Objective : Acromegaly is associated with excessive GH and IGF- 1 concentrations that lead to deranged glucose homeostasis by increasing peripheral insulin resistance , impairing muscle and adipose uptake of glucose , and increasing lipolysis and
hepatic gluconeogenesis . Patients with acromegaly experience increased rates of diabetes mellitus and hypertriglyceridemia.
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X 24 . A 45 -year- old woman is brought to the emergency department 30 minutes after the sudden onset of left - sided facial drooping and left arm and leg weakness . One week ago , she returned from a business trip that involved a 6 -hour airplane flight. She has no
history of major medical illness . She does not smoke. Her only medications are an oral contraceptive and occasional acetaminophen for headache . Her pulse is 88 / min and regular, and blood pressure is 160/90 mm Hg . Physical examination shows left-
sided facial paralysis. Examination of the left lower extremity shows swelling , tenderness , and localized erythema over the caif . Muscle strength is 3 / 5 in the left upper and tower extremities . Cardiac examination shows no abnormalities . Echocardiography is
most likely to show which of the following findings in this patient?
A ) Aortic stenosis
B ) Endocarditis
C ) Hypertrophy of the interventricular septum
D ) Mitral valve prolapse
E ) Patent foramen ovale
Correct Answer : E
This patient with a deep venous thrombosis (DVT ) most likely possesses a patent foramen ovale , allowing a thromboembolism to bypass the pulmonary circulation and cause a thromboembolic cerebrovascular accident (CVA . or stroke). DVT typically presents with
lower extremity edema , erythema warmth , and pain at rest along with calf pain on dorsiflexicn of the foot (Homan sign) . Blood clots typically occur in patients who possess some or all of the risk factors of the Virchow triad : stasis (long flight, postoperative
,
immobility), hypercoagulability (oral contraceptive use, hypercoagulable disorders ): and endothelial damage (smoking hypertension atherosclerosis , injury ). DVT may lead to pulmonary embolism if the clot embolizes to the right heart and subsequently to the
, ,
pulmonary circulation . Jr patients with a patent foramen ovale ( a congenital defect between the right and left atria) , the clot may travel from the right atrium to the left atrium and then to the systemic circulation This patient 's clot likely embolized to the right internal
carotid artery and then the right middle cerebral artery (MGA) occluding blood flow to the right primary motor cortex resulting in ieft-sided weakness. CVAs occur because of ischemic or hemorrhagic loss of blood supply to the brain . Approximately 80 to 85% of
;
CVAs are ischemic , commonly arising from thromboembolic disease , whereas 15 to 20% of CVAs are hemorrhagic as a result of blood vessel rupture ( eg. hypertension - related intraparenchymal hemorrhage from a perforating artery ). Classically, CVAs manifest as a
neurologic deficit related to the affected part of the brain.
Incorrect Answers : A, 0. C, and D.
Aortic stenosis ( Choice A), hypertrophy of the interventricular septum (Choice C). and mitral valve prolapse ( Choice D) are structural abnormalities of the heart that lead to abnormal cardiac outflow which may result in volume overload and left atria enlargement
,
over time . Hemostasis (blood pooling ) in the enlarged left atrium increases the risk for thromboembolic stroke . However, this patient 's physical examination shows a DVT as the source of the thromboembolism . The classic example of this scenario is left atrial stasis
in the setting of atrial fibrillation from mitral stenosis, left ventricular hypertrophy, or chronically increased afterload (eg hypertension , aortic stenosis).
;
Endocarditis ( Choice B) refers to an infection of the endocardium , which may feature valvular vegetations. These vegetations may embolize to the brain However, this patient's physical examination shows a DVT as the source of the occlusion instead. This patient
lacks physical examination findings concerning for endocarditis (eg : splinter hemorrhages , Osier nodes . Janeway lesions ) .
Educational Objective : Patients with the risk factors of Virchow triad (stasis hypercoagulability, and / or endothelial damage) may develop deep venous thrombosis (DVT) . A DVT can embolize to the pulmonary circulation , resulting in pulmonary embolism. However
,
in patients with a patent foramen ovale , thromboembolism from DVT may bypass the pulmonary circulation and cause a thromboembolic stroke .
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25. A 57-year- old man dies 5 days after a stroke . He had progressively severe hypertension over the past 2 years but refused treatment . Blood pressure just prior to the stroke was 220/ 110 mm Hg . Which of the following is the most likely histologic finding in his
kidneys at autopsy?
A ) Amyloidosis
B ) Chronic pyelonephritis
C ) Hyperplastic arteriolitis
D ) Nodular glomerulosclerosis
E ) Renal papillary necrosis
Chronic hypertension is associated with vascular changes in the small arteries and arterioles called arteriosclerosis marked by thickening of the vessel walls and loss of elasticity . There are two primary types: which are hyaline arteriosclerosis and hyperplastic
,
arteriosclerosis (also called hyperplastic arteriolitis ) . Hyaline arteriosclerosis is characterized by protein deposition in the vessel walls . Hyperplastic arteriosclerosis is characterized by concentric thickening of the vessel wall with a laminar appearance caused by the
proliferation of smooth muscle cel s and is associated with severe , chronic hypertension as in this patient .
,
Incorrect Answers : A, B. D, and E.
Amyloidosis ( Choice A ) is an infiltrative disorder caused by the deposition of abnormal proteins in tissue . The kidneys are commonly involved, with abnormal protein deposits in the mesangium that display an apple -green birefringence with Congo red dye on
histologic analysis . Renal impairment and nephrotic syndrome may develop . It is not caused by chronic hypertension.
Chronic pyelonephritis (Choice B) may develop from recurrent infections of the genitourinary tract with reflux into the renal pelvis which may occur in the setting of obstructive uropathy nephrolithiasis, and vesicoureteral reflux . The kidneys display atrophy, calyceal
,
deformities , and fibrosis of the renal parenchyma .
Nodular glomerulosclerosis ( Choice D) is associated with diabetic nephropathy and amyloidosis it may progress to nephrotic syndrome.
,
Rena! papillary necrosis ( Choice E) may result from severe ischemic injury to the kidney. Risk factors include sickle cell disease obstructive nephropathy, nonsteroidal anti - inflammatory analgesic use . diabetes meJIitus, and severe pyelonephritis .
,
Educational Objective: Chronic hypertension can result in arteriosclerosis , which commonly affects the renal arterioles . Histologic changes associated with hyperplastic arteriosclerosis include laminar thickening of the vessel wall caused by smooth muscle
proliferation.
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26. A 65 -year- old woman dies 6 months after the onset of severe headaches . Her brain as seen at autopsy is shown in the photograph . Which of the following is the most likely cell of origin of this neoplasm?
A ) Astrocyte
B ) Endothelial
C ) Melanocyte
D ) Meningeal
E ) Squamous epithelial
Meningiomas are the most common primary brain tumors in adults and arise from the meninges (the protective coverings of the brain). This patients meningioma is pictured along the inferior aspect of the forebrain within the anterior interhemispheric fissure
between the frontal lobes, resulting in significant mass effect and compression of the adjacent frontal lobes and olfactory bulbs . Patients may be asymptomatic or experience seizures or focal neurologic deficits related to the tumor location . Meningiomas are
typically benign but can be malignant . Malignant meningiomas may grow rapidly, leading to symptoms of increased intracranial pressure (postural headache , nausea , papilledema) , or may metastasize . Meningiomas appear as well-circumscribed extra -axial
,
(outside of the brain parenchyma) masses that compress the parenchyma , as in this patient . Treatment may include surgical resection to alleviate the tumoral mass effect if significant .
Incorrect Answers : A, B. C . and E.
Astrocytes ( Choice A ) proliferate to form glial tumors in adults , for example , glioblastoma . These highly malignant tumors appear as intra -axial masses in the cerebral hemispheres , which typically demonstrate areas of necrosis and can spread to the opposite
hemisphere across the corpus callosum .
Endothelial cel s ( Choice B ) may proliferate to form hemangioblastomas . Hemangioblastomas typically arise in the posterior fossa as intra- axial tumors .
Tumors arising from melanocytes (melanomas) ( Choice C ) or squamous epithelial cells (squamous cel carcinomas) (Choice E) are primarily extracranial and would not compress the brain. Brain metastases from these malignancies would most likely be intra -
axiai rather than extra -axial .
Educational Objective : Meningiomas are the most common primary brain tumors in adults. Malignant meningiomas may grow rapidly and cause symptoms of increased intracranial pressure such as headache. Meningiomas appear as well-circumscribed extra- ,
axial masses that compress the adjacent brain parenchyma .
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27. A study is conducted in which the right renal artery of an experimental animal is constricted to decrease arcuate artery pressure by 20 mm Hg. Measurement of inufin clearance shows that renal artery constriction has no effect on glomerular filtration rate
(GFR ) . Which of the following best explains the maintenance of a constant GFR in this experiment?
A ) Decreased glomerular filtration coefficient

B ) Decreased glomerular hydrostatic pressure
C ) Decreased renal blood flow
D } increased afferent arteriolar resistance
E ) Increased efferent arteriolar resistance
F ) Increased renal blood flow
Correct Answer : E
Autoregulation is an essential process for maintaining perfusion of end organs despite variations in systemic blood pressure and takes place in numerous organs throughout the body. Renal autoregulation is adapted to produce a relatively constant GFR despite
changes in glomerular perfusion and is mediated by the delivery of filtered sodium to the macula densa in the early distal convoluted tubule . In renal artery stenosis, there is decreased glomerular perfusion. Reductions in glomerular perfusion result in decreased
filtration and decreased sodium delivery to the macula densa. The macula densa compensates for this by promoting activation of the renin-angiotensin system by stimulating the juxtaglomerular apparatus to secrete renin , which subsequently causes an increased
angiotensin ll-mediated constriction of the glomerular efferent arteriole . This causes increased efferent resistance and induces an increased intraglomerular pressure to maintain GFR . Systemic hypertension can also be counteracted by renal autoreguiation through
a similar but opposite mechanism . As with all autoreguiatory systems , rena] autoregulation is only able to maintain glomerular filtration within a particular range of systemic blood pressures and can be overwhelmed by either profound hyper- or hypotension .
Incorrect Answers : A . B . Ca D, and F.

Decreased glomerular filtration coefficient ( Choice A) is not a mechanism of renal autoregulation . The glomerular filtration coefficient is an inherent property of the renal capillary and is not freely modified in response to changes in blood pressure. Some diseases
that result in glomerular capillary damage , such as diabetes mellitus , may decrease the filtration coefficient .
Decreased glomerular hydrostatic pressure ( Choice B) would result in decreased glomerular filtration and exacerbate the hypofiltration of sodium that underlies the mechanism of renal autoregulafion .
Decreased renal blood flow ( Choice C) is the direct result of the experimental constriction of the renal artery. This answer choice describes the effects of the experimental intervention rather than the physiologic mechanisms that compensate for this intervention .
Increased afferent arteriolar resistance ( Choice D ) would also result in decreased glomerular filtration and exacerbate the hypofiltration of sodium that underlies the mechanism of renal autoregulation .
Increased renal blood flow ( Choice F) would not be observed following experimental constriction of the renal artery. Autoregulation does rot alter renal blood flow itself , but rather maintains GFR despite changes in renal blood flow.
Educational Objective: Renal autoregulation is mediated by the delivery of filtered sodium to the macula densa . Hypoperfusion of the glomerulus leads to decreased sodium filtration, and activation of the renin- angiotensin system by the macula densa , which causes
angiotensin : l -mediated constriction of the glomerular efferent arteriole and a consequent increase in intraglomerular pressure and GFR .
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28. A 23-year- old woman comes to the physician because of a 1 -week history of intermittent episodes of fever and chills, followed by a rash. She has had four operations to correct scoliosis, in addition to undergoing a tonsillectomy an appendectomy removal
, ,
^
of a lipoma from her scalp and dermabrasion to correct acne scarring. She was admitted to :he hospital 1 year ago for 2 weeks because of nausea and vomiting of unexplained origin . Her temperature is 37 C (98.6 T ) . Physical examination shows
;
approximately 12 evenly spaced punctate marks in a linear pattern on the abdomen and upper and lower extremities . There are no marks on the face or back . Which of the following is the most likely diagnosis ?
A ) Acute myelogenous leukemia

B ) Factitious disorder
C ) Immune thrombocytopenic purpura
D ) Lyme disease
E ) Syphilis
In factitious disorder patients consciously produce symptoms (ie : purposely injure themselves) for primary gain. Primary gain is the motivation to be cared for which constitutes an unconscious motivator for the patient's conscious production of symptoms . Early
losses , neglect or abuse may disrupt patient identity and relationships, and adopting the sick role may represent an attempt to cope with stress and stabilize their identity and relationships . This young patients extensive history of elective surgeries and hospita
,
admissions illuminate a pattern of care seeking and linearly spaced punctate marks are consistent with self-inflicted puncture wounds rather than a known disease . Treatment includes regular follow- up with one physician who oversees management (as apposed to
,
symptom-triggered appointments) and possible psychotherapy.
incorrect Answers : A . C , D , and E.
Acute myelogenous leukemia ( Choice A) is a hematologic cancer resulting from the malignant transformation of myeloid precursor cells . Proliferated myeloid precursor cells may deposit in soft tissues and present as nodules or plaques . Punctate lesions would be
atypical.
Immune thrombocytopenic purpura ( Choice C } is an acquired thrombocytopenia resulting from autoantibodies against platelet antigens . Patients may present with a petechial or purpuric rash in dependent body regions ( eg . feet . legs and hands) rather than
,
punctate marks on the abdomen and legs .
Lyme disease ( Choice D) is a tick-borne illness that may initially present with erythema migrans , a lesion that forms around the site of the tick bite . The lesion may develop central clearing . Multiple punctate lesions would be inconsistent with Lyme disease .
Patients with syphilis ( Choice E ), a sexually transmitted spirochete infection, may demonstrate a diffuse macular or papular rash that involves the trunk and extremities (including the palms and soles) during secondary syphilis or may present with gummatous
disease during tertiary syphilis, which can manifest as singular or multiple ulcerative or granulomatous lesions . Punctate marks in a linear pattern would be atypical.
Educational Objective: In factitious disorder patients consciously produce symptoms ( ie . purposely injure themselves) for primary gain . A history of multiple procedures and subjective or objective findings that are inconsistent with known diseases suggest factitious
disorder.
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29. A 28 -year- old woman delivers a full -term newborn who has generally flattened facial features including a broad , flat nose : and bilateral clubfoot deformity with tibial torsion. Ultrasonography at 18 weeks' gestation showed oligohydramnios and small
,
dysplastic fetal kidneys with scattered cysts. Which of the following general classifications best describes the extrarenal physical features ?
A ) Deformation
B ) Disruption
C ) Malformation
D ) Multifactorial
E ) Teratogenic effect
Deformation describes a disruption in organ morphogenesis that occurs after the embryonic period . It arises because of an extrinsic force that limits normal development in this example, renal dysplasia has resulted in minimal fetal urine production and therefore
,
limited production of amniotic fluid ( oligo- or anhydramnios) as fetal urine is a major contributor. Without the production of amniotic fluid to distribute force evenly over the surface of the developing fetus deformities will result . Fetuses with renal agenesis or dysplasia
typically exhibit compressed flattened facial features : limb dysplasia , and puimonary hypoplasia caused by inadequate amniotic fluid - induced lung expansion Tnis is known as the Potter sequence and* is an example of an extrinsic influence on organ
;
morphogenesis from an inadequate intrauterine environment.
Incorrect Answers : B, C : D: and E.
Disruption ( Choice B } defines an error in organ morphogenesis that arises from the breakdown of an organ or body region that was developmental normal . The classic example of disruption is the presence of amniotic bands that constrict compress, or encircle the
developing fetus, resulting in morphogenic abnormalities involving , for example, the limbs : pents : fingers: or toes .
Malformation ( Choice C) defines an intrinsic disruption in organ development, which generally occurs earlier in the embryonic period .
Multifactorial ( Choice D ) defines the presence of many influences that result in organ morphogenic errors , an example of which could be a fetus exposed to alcohol in utero with resultant abnormal facial development that also experienced disruption from amniotic
bands later in utero .
Teratogenic effect ( Choice E) describes the result of embryonic exposure to an external toxic substance (often a medication or illicit drug) that results in malformation . Examples include the maternal use of ACE inhibitors , which impair fetal renal development ,
lithium, which is classically associated with an atrialized right ventricle, and thalidomide , which is known to cause limb deformities .
Educational Objective : Deformation describes a disruption in organ morphogenesis that occurs after the embryonic period . It arises because of an extrinsic force that I mits normal organ development .
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30 . A transgenic animal containing a targeted mutation in the gene coding for macrophage colony-stimulating factor is prepared . Which of the following generalized skeletal ahnormalities is expected in this animal?
A ) Achondroplasia
B ) Osteomalacia
C ) Osteopetrosis
D ) Osteoporosis
E ) Skeletal agenesis
Osteopetrosis is a rare , inherited condition in which an imbalance in the function of osteoclasts and osteoblasts arises: leading to excess bone mineral deposition with resulting dense abnormally mineralized bones . Consequences of imbalanced bone density m
,
osteopetrosis include early mineralization and fusion of the physis with stunted growth, cranial nerve impingement with resultant blindness, deafness: or loss of cranial nerve function , bone pain craniosynostosis , scofiosis : hypoca!cemi.a: anemia and
; ,
immunodeficiency. In contrast conditions of low bone density such as osteoporosis generally present with fragility fractures. There are many genetic causes of osteopetrosis : with the final common pathway being the failure of the osteoclast to appropriately resorb
bone. Genetic mutations may include channelopathies ( CLCN7 ) , receptor activator of nuclear factor kappa- Ei ligand ( RANKLE the RANK receptor or carbonic anhydrase (CA2} deficiencies The net effect of any such defect is impaired resorption by the osteoclast .
Osteoclasts originate from the monocyte-macrophage lineage (a hematopoietic line ) ; therefore , mutations that inactivate macrophage colony- stimulating factor would prevent differentiation of these cells . RANKL. is also required for their differentiation and activation.
By contrast , osteoblasts arise from mesenchymal stem cells. Osteoclasts are large , multinucleated cells found in pits at the surface of bone , where they produce matrix metalIo proteases , cathepsins . and hydrogen ions , which dissolve bone matrix .
Incorrect Answers : A , Bp D . and E.
Achondroplasia (Choice A) results in impaired growth of long bones caused by an autosomal dominant mutation in the fibroblast growth factor receptor 3 ( FGFR3 ) gene . Affected patients have short extremities and a torso of normal length . Intelligence is generally
unaffected , but patients may experience sleep apnea caused by craniofacial obstructive effects . Homozygous dominance is generally fatal by infancy, at the latest .
Osteomalacia ( Choice B) is a condition of imbalanced bone mineral deposition that results in inappropriately soft bones , generally arising from dietary vitamin D deficiency or impaired calcium resorption .
Osteoporosis (Choice D) defines a state of low bone mineral density and is common among postmenopausal women . The etiology is multifactorial with genetic predisposition and environmental influences leading to the phenotype.
Skeletal agenesis ( Choice E) describes a heterogeneous group of conditions in which all or part of a bone fails to develop . This may be primary , as in fibular hemimelia . or related to multiple malformations , as seen in caudal regression syndrome .
Educational Objective: Osteopetrosis describes a disease of excessive mineralization of bone, leading to abnormally dense bone. It results from failure of osteoclastic resorption . The osteoclast arises from the monocyte -macrophage lineage , and defects in signaling
of macrophage colony -stimulating factor may play a role in the pathogenesis.
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31. A 50 -year- old man is brought to the emergency department because of a 2 - hour history of vomiting blood He is in acute distress . His temperature is 37.5°C ( 99.5°F ), pulse is 110/min ,
respirations are 18,'min, and blood pressure is 80/50 mm Hg . Despite appropriate treatment, he dies shortly thereafter, and an autopsy is done . The gross and microscopic appearances of a
section of the esophagus are shown . Which of the following best explains these autopsy findings?
A ) Angiosarcoma
B ) Candidiasis
C ) Cytomegalovirus infection
D ) Esophageal carcinoma
E ) Gastric metaplasia -
^-
F ) Hemangioma
G ) Miliary tuberculosis
m *
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H ) Portal hypertension
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Correct Answer : H .
The microscopic findings taken from the esophageal sample demonstrate dilation of the submucosal venous plexus. This correlates with the dilated vessels seen on the gross specimen The inferior esophageal veins drain into the left gastric vein and then into the
portal vein Tliey are part of the portal venous system , a series of interconnected veins that drain blood from the colon small intestines spleen , liver stomach , and inferior esophagus . While this blood eventually makes its way to the systemic circulation via the
, , ,
inferior vena cava , it must first pass through the liver. Jn cirrhosis, obliteration of the hepatic sinusoids through progressive fibrosis increases the resistance to blood flow through the liver, which is transmitted to the portal venous system causing portal hypertension
(PH ) . Increased venous pressure is transmitted to all the veins which drain into the portal vein , including the inferior esophageai veins, resulting in esophageal varices after they are engorged . Jn addition to esophageal varices , manifestations of PH include gastric
varices, caput medusae , hemorrhoids splenomegaly, and ascites . The risk for acute gastrointestinal bleeding from esophageal varices Is high . It presents with large volume hematemesis followed by hemodynamic collapse if untreated .
,
Incorrect Answers : A . B. C . D , E . F. and G .
Angiosarcoma (Choice A) and hemangioma ( Choice F) are both vascular neoplasms caused by proliferation of endothelial cells. Angiosarcoma is a malignant vascular neoplasm which is characterized by large , atypical endotheiia cells and vascular slit-like :
spaces . In contrast , hemangioma is a proliferation of benign endothelial cells creating duplicated vascular channels . This histopathoiogy does not demonstrate cellular atypia and the number of vascular channels is normal , only they are dilated .
Esophageal candidiasis ( Choice B) is seen in HIV patients and presents with white friable patches on the mucosa of the esophagus . It is commonly accompanied by oral candidiasis . It causes dysphagia , but not large volume hematemesis and hemodynamic
,
instability.
Cytomegalovirus ( GMV) infection ( Choice C ) is an opportunistic infection commonly occurring in immunocompromised patients In the setting of solid -organ or allogeneic bone marrow transplantation or HIV,' AIDS . When causing esophagitis linear ulcers are ,
characteristic . Large volume hematemesis is not a feature of CMV esophagitis .
Gastric metaplasia ( Choice E ) is a complication of longstanding gastritis. Persistent mucosal irritation and inflammation leads to replacement of the normal gastric epithelium with columnar, intestinal epithelium . Untreated , this can increase the risk for developing
gastric carcinoma. Similarly intestinal metaplasia of the distal esophagus secondary to longstanding gastroesophageal reflux (Barrett esophagus ) increases the risk for developing esophageal carcinoma ( Choice D) These are less likely a cause of large volume
hematemesis than esophageal varices .
Miliary tuberculosis ( Choice G) is caused by hematologic dissemination of Mycobacterium tuberculosis. The esophagus is an unlikely site of miliary tuberculosis. Miliary tuberculosis commonly involves the lymphatic system , bones , fiver, and centra! nervous
system and is usually accompanied by fever and night sweats.
Educational Objective : Esophageal varices appear microscopically as dilated submucosal veins . They are caused by portal hypertension in which the resistance generated by a cirrhotic liver is conveyed through the portal venous system and portosystemic shunts.
Esophageal varices are at a high risk for bleeding leading to hematemesis and hemodynamic instability.
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32 . A 70-year- old man comes to the physician because of a 3- day history of shortness of breath and right-sided chest pain . His respirations are 25/mifL Chest x-rays show a right pleural effusion and an associated ipsiEateral . scallop -shaped pleural density.
Examination during an open fung biopsy shows a thick : firm, white pleural tumor that ensheathes the right lung . Which of the following Is the strongest predisposing risk factor for this patient's condition?
A ) Family history of lung cancer

B ) Radiation therapy
C ) Raising pigeons
D ) Smoking cigarettes
E ) Working in a shipyard
Correct Answer : E
Chronic cough : shortness of breath and pleural effusion plus a calcified pleural plaque or x-ray is consistent with a diagnosis of malignant mesothelioma , which can be confirmed by biopsy. Development of malignant mesothelioma is strongly associated with
,
pulmonary asbestosis A history of working in a shipyard is a known risk factor for exposure to asbestos , along with roofing and plumbing. Asbestosis is a progressive fibrotic disease that manifests decades after exposure . Long -term complications include interstitial
fibrosis , chronic respiratory failure, and malignancy ( especially malignant mesothelioma and bronchogenic carcinoma). Malignant mesothelioma typically presents with an exudative pleural effusion caused by the malignant pleural disease. Treatment includes
chemotherapy, surgical resection, and radiation .
Incorrect Answers : A . B C . and D.

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Family history of lung cancer ( Choice A ), radiation therapy ( Choice B) , and smoking cigarettes (Choice D) are risk factors for developing primary bronchogenic carcinoma . Asbestosis is also a risk factor for bronchogenic carcinoma , although it also has a strong
association with the development of malignant mesothelioma.
Raising pigeons ( Choice C ) is a risk factor for chronic hypersensitivity pneumonitis an inflammatory condition of the lungs in response to environmental irritants The condition may progress to pulmonary interstitial fibrosis and the chronic inflammation increases the
, ,
risk for developing primary bronchogenic carcinoma .
Educational Objective : Asbestosis is a chronic progressive pulmonary disorder associated with interstitial fibrosis and an increased risk for both primary bronchogenic carcinoma and malignant mesothelioma . Occupational risk factors for asbestos exposure include
shipbuilding , roofing , and plumbing .
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33. A 5 G -year- old woman comes to the physician because of a 3 -week history of increasing weakness of her arms and legs . She has smoked 1 pack of cigarettes daily for 30 years. Physical examination shows pronounced weakness of the hip girdle muscles
and lesser weakness of the shoulder girdle muscles: both of which improve with repetitive testing. A chest x-ray shows a hilar lung mass. Electromyography is compatible with a malfunction of the neuromuscular junction . Impairment of which of the following
is the most tikely cause of these findings?
A ) Acetylcholinesterase
B ) Binding of acetylcholine on the postsynaptic membrane
C ) Direct depolarization of muscle fibers by Ca 2:+
D ) Postsynaptic membrane potential
E ) IPresynaptic release of acetylcholine
Correct Answer : E
Lambert-Eaton myasthenic syndrome (LEMS ) is an uncommon neurologic condition that affects neuromuscular junction transmission . Normally action potentials lead to depolarization in the terminal bouton of the axon. Voltage -gated calcium channels consequently
open and allow calcium influx , which triggers the exocytosis of neurotransmitter - filled vesicles into the synaptic cleft . Patients with LEMS possess antibodies to voltage-gated calcium channels on presynaptic lower motor neurons , which decreases calcium influx and
acetylcholine release to postsynaptic skeletal muscle ceHs. This patient with a smoking history and central lung mass likely has a small cefl lung cancer that is producing autoantibodies to the voltage -gated calcium channel, causing a paraneoplastic LEMS. Patients
consequently demonstrate progressive proximal muscle weakness with depressed or absent deep tendon reflexes. The muscle weakness typically improves with repetitive motion and exercise as small amounts of acetylcholine accumulate in the synaptic cleft over
1ime increasing the frequency of postsynaptic action potentials in skeletal muscle cells . Autonomic symptoms such as decreased salivation and consequent dry mouth may also occur The diagnosis may be confirmed with nerve conduction studies and
;
electromyography with exercise testing . Removal of the antibody - producing malignancy is crucial for treatment .
Incorrect Answers : A . B . C, and D.
Acetylcholinesterase ( Choice A ) inhibition leads to decreased degradation of synaptic acetylcholine and is the mechanism of medications (eg : pyridostigmine) utilized for myasthenia gravis. This mechanism typically improves muscle strength and would not be
expected to lead to the progressive muscle weakness demonstrated in LEMS .
Impairment of the binding of acetylcholine on the postsynaptic membrane ( Choice B ) is the cause of myasthenia gravis. Myasthenia gravis is an autoimmune disorder of neuromuscular transmission that presents with muscle weakness and fatigability (versus the
postexercise facilitation demonstrated in LEMS) . Additiona ly: myasthenia gravis is more likely to affect the distal extremity and ocular musculature than LEMS.
Direct depolarization of muscle fibers by Ca 2 + ( Choice C ) is not a known mechanism of neuromuscular junction transmission. Postsynaptic depolarization is mediated by sodium influx via nicotinic acetylcholine receptors.
The postsynaptic membrane potential ( Choice D ) may be decreased in LEMS secondary to the decreased presynaptic release of acetylcholine .
Educational Objective: Patients with Lambert-Eaton myasthenic syndrome (LEMS) possess antibodies to voltage-gated calcium channels on presynaptic lower motor neurons , which decreases calcium influx and acetylcholine release to postsynaptic skeletal muscle
cells in some patients , malignancies (eg , small cell lung cancer) trigger production of these antibodies , resulting in paraneoplastic LEMS Patients present with progressive proximal muscle weakness that improves with repetitive motion and exercise.
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Exam Section 1: Item 3+ ol 50 National Board of Medical Examiners^
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34 . An 83-year -old woman is brought to the physician by her daughter to discuss the results of a complete dementia work-up . The patient has had mild memory impairment for 8 months. She takes no medications . Vital signs are normal . Her Mini-Mental State
Examination score is 23/30 . A rapid plasma reagin is 1: 4. and a microhemagglutination assay for Treponema pallidum is positive. Which of the following is the best next step for the physician?
A ) Discussion of the diagnosis with the daughter privately

B ) Discussion of the diagnosis with the patient privately
C ) Disregarding the results since the patient is too old for treatment
D ) Repeated tests
E ) Lumbar puncture
This patient's syphilis diagnosis should be discussed with her privately. All patients , including those with dementia should be assumed to possess decisional capacity to make medical decisions unless the physician determines the patient does not possess
,
decisionai capacity. This physician should first discuss this sensitive diagnosis with the patient privately and assess her decisional capacity surrounding the diagnosis. Patients who are deemed to lack decisional capacity should still be informed of the diagnosis ,
which may give the patient a partial understanding of their situation and relieve potential distress about the diagnostic uncertainty. The next- of-kin or designated medical decision maker of a patient without decisional capacity should also be informed after the
diagnosis is discussed with the patient . Neurosyphilis refers to the spread of syphilis to the central nervous system. Neurosyphilis can manifest as meningitis : a progressive dementia syndrome known as genera! paresis: or disease of the posterior columns of the
spinal cord known as tabes dorsalis . Diagnosis involves confirming the diagnosis of syphilis with both treponemal and nontreponemal ( eg: rapid plasma reagin and VDRL ) serum testing fallowed by examining the cerebrospinal fluid ( CSF) and performing CSF
treponemal or nontreponemal tests. Treatment of neurosyphilis is crucial to prevent neurologic progression and requires the administration of penicillin G .
incorrect Answers : A . C D , and E.

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Rather than discuss this sensitive diagnosis with the patient ' s daughter ( Choice A ) the physician should honor this patient' s autonomy by first discussing the diagnosis with the patient . After this discussion , if the physician believes that the patient lacks decisional
;
capacity and the daughter is the next- of-kin or a designated medical decision-maker then the physician should discuss the diagnosis and management plan with the daughter. If the patient possesses decisional capacity and the daughter wishes to be informed of
her mother 's medical situation the physician should ask the patient 's permission to share the diagnosis with her daughter or encourage the patient to share the diagnosis with her daughter herself .
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There is no age limit for syphilis treatment ( Choice C). This patient with neurosyphi is should be treated with antibiotics to prevent progression of the neurologic manifestations.
Repeated tests are unnecessary ( Choices D) . Since both a treponemal and nontreponemal serum test were positive , this patient has a confirmed syphilis diagnosis.
Though cerebrospinal ftu; d testing from a iumbar puncture confirms the diagnosis of neurosyphilis (Choice E) the physician first needs to discuss the syphilis diagnosis with the patient and determine the patient's decisional capacity. The physician can then obtain
;
the patient's ( or next -of- kin's ) informed consent for the lumbar puncture.
Educational Objective: Neurosyphilis, or the spread of syphilis to the central nervous system , may present with a progressive dementia. All patients, including those with dementia , should be assumed to possess decisional capacity to make medical decisions unless
the physician determines the patient does not possess decisional capacity. Physicians should therefore discuss new diagnoses , such as syphilis , with patients privately before discussing the diagnosis with family members or proceeding with further management
steps.
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35. A 22 -year- old primigravid woman at 20 weeks ' gestation comes to the physician because of a 4-day history of dull pelvic pain that radiates to the right side of her labia majora . She says , ' It feels fiike something is pulling / ' She is concerned that she is going
into labor. Physical examination shows no dilation of the cervix . Stretching of which of the following ligaments is the most likely cause of this patient' s pain?
A ) Broad ligament
B ) Mesosalpinx
C ) Round ligament
D } Suspensory ligament of the ovary
E ) Uterosacral ligament
The round ligament of the uterus is a fibromuscular band of tissue that extends from the superolateral part of the uterus where the fallopian tubes insert passes through the inguinal canal and ends in the labia majora . It is a remnant of the gubemaculum , an
,
embryonic structure which assists in the descent of the gonads. In pregnancy, as the uterus increases in size , the round ligament becomes stretched . Increased concentration of the hormone relaxin during pregnancy also contributes to its stretching . Relaxin allows
for the ligaments of the pelvis and hip girdle to stretch so the birth canal can accommodate the fetus during delivery. The combination of increased elasticity and increased size of the uterus strains the round ligament and commonly ieads to pain during pregnancy.
Sudden movements or vigorous activity may precipitate this pain . There is no association of round ligament pain with preterm labor , but other causes of abdominal pain during pregnancy should be ruled out before attributing pain to the round ligament . No treatment
is necessary, as the pain is self-limited and typically mild .
Incorrect Answers : A . B D . and E.

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The uterus is supported by the broad ligament ( Choice A ) which attaches to the superior aspect of the uterus and is a layer of peritoneum . The mesometrium , mesosalpinx ( Choice B ) , and mesovarium are named portions of the broad ligament . While these
structures are all contiguous , the mesometrium covers the uterus and creates the majority of the broad ligament , the mesosalpinx covers the fallopian tubes , and the mesovarium covers the ovaries. Stretching of this ligament during pregnancy does not cause labial
pain .
The suspensory ligament of the ovary ( Choice D ) extends laterally from the ovary to the wall of the pelvis and runs adjacent to the ovarian artery and vein . Its size does not significantly change in pregnancy.
The uterosacral ligament ( Choice E) holds the uterus in place in the pelvis it is a paired structure which connects the uterus to the sacrum at the level of the cervix They may also be called the rectouterine ligaments or sacrocervical ligaments . It is not the cause of
,
this patient ' s pain.
Educational Objective: The round ligament of the uterus is a fibromuscular band of tissue that extends from the superolateral part of the uterus where the fallopian tubes insert , passes through the inguinal canal and ends in the labia majora . Stretching of the round
,
ligament commonly leads to pain during pregnancy.
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36. An investigator is studying Po 2 in an experimental animal . It is found that Po 2 in the renal vein is relatively high compared with venous Po 2 from most other organs . Which of the following best explains this finding?
A ) Bicarbonate reabsorption causes a Bohr shift of the oxyhemoglobin dissociation curve of the renal vein
B ) Blood flow per gram of tissue is greater in kidneys than in other organs
C ) Erythropoietin synthesized in the kidneys increases local hematocrit and Po 2
D ) Fenestrations in glomerular capillaries promote the convective transport of 02 from Bowman space to the efferent arteriole
E ) Most of the active transport to form urine in the kidney occurs in the renal podocytes
The kidneys receive approximately one-fourth to one-fifth of total cardiac output, and because of the small size of the kidneys they receive among the largest blood flow per gram of tissue. Blood flow functions to provide oxygen and nutrients . In the kidneys an
; ;
additional function of blood flow beyond native supply of the organ parenchyma is to contribute to filtration of plasma to create ultrafiltrate and urine . Thus the blood flow in the kidney is in excess of what is needed to meet its metabolic demands . This results in a
;
small difference in arterial and venous Po and Po 2 in the renal vein is relatively high compared to other organs that depend on blood flow to meet local metabolic demand .
^
Incorrect Answers : A , C D, and E.
;
Shifting of the oxyhemoglobin dissociation curve ( Choice A ) describes hemoglobin' s sigmoidal affinity for oxygen depending on the partial pressure of oxygen. The oxyhemoglobin dissociation curve can shift and is affected by H + and the partial pressure of COs not
bicarbonate. Other factors that can affect the oxyhemoglobin dissociation curve include exercise , altitude, and temperature .
Erythropoietin is a hormone produced by kidneys that stimulates proliferation of erythrocytic progenitors in the bone marrow. It does not increase local hematocrit and Po 2 ( Choice C).
Fenestrations in glomeruiar capillaries do not promote the convective transport of 02 from Bowman space to the efferent arteriole ( Choice D). Fenestrations in the glomerulus function for the filtration of plasma solutes and water to create ultrafiltrate in the Bowman
space.
Most of the active transport to form urine in the kidney does not occur in the renal podocytes ( Choice E ) . The renal podocytes are cells in the Bowman space , which is the first site of filtration . Filtration between the glomerulus and Bowman space is secondary to
hydrostatic and oncotic pressures , not as a result of active transport .
Educational Objective: The kidney ' s relatively low metabolic demands compared with high blood flow results in a small difference in renal arterial and venous Po 2. The Po 2 in the renal vein is relatively high compared to other organs that depend on blood flow to
meet local metabolic demands .
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37. A previously healthy 1 8- year -old man is brought to the emergency department by his mother 45 minutes after she found him crouched in his closet , saying he had to hide from the intruders "from that other place .' There were no intruders in the house. He
1
has no history of alcohol or drug use . He appears afraid of the physician and sits far away from her. During the interview, he says he has heard two male voices in his head for the past 2 weeks. Physical examination and laboratory studies show no
abnormalities. Which of the following is the most likely diagnosis?
A ) Bipolar disorder
B ) Brief psychotic disorder
C ) Delusional disorder
D ) Schizoaffective disorder
E ) Schizophrenia
This patient meets the diagnostic criteria for brief psychotic disorder. Brief psychotic disorder is characterized by the acute onset of one or more psychotic symptoms (eg , delusions hallucinations , disorganized speech , disorganized behavior ) lasting less than one
,
month. This patient is experiencing a paranoid de usion , disorganized behavior (crouching in his closet despite the absence of an intruder) , and auditory hallucinations . Risk factors for brief psychotic disorder inc ude stressful life events and personality disorders .
Treatment may include hospitalization and antipsychotic treatment depending on symptom severity and functional impairment , though some symptoms and the presentation overall may resolve without medications.
Bipolar disorder ( Choice A) is characterized by discrete episodes of depression and mania, which can sometimes be accompanied by psychotic symptoms such as hallucinations and delusions. This patient demonstrates psychotic symptoms without evidence of
mood symptoms , which makes a primary psychotic disorder such as brief psychotic disorder more likely.
Delusional disorder ( Choice C ) features one or more delusions for a month or longer without other psychotic symptoms . This patient does not meet the duration criterion for delusional disorder and demonstrates disorganized behavior and auditory hallucinations ,
which are atypical of delusional disorder.
Patients with chronic psychotic disorders such as schrzoaffective disorder ( Choice D) or schizophrenia ( Choice E) demonstrate at least two of the following five symptoms: delusions , hallucinations disorganized speech disorganized behavior, or negative symptoms
,
(eg , flat affect , apathy, alogia). Many patients also illustrate prodromal periods of strange behavior and decreased functioning. Patients with schizoaffective disorder experience these psychotic symptoms in the absence of mood symptoms though also experience
prominent depressive or manic symptoms . The total duration of symptoms must exceed six months to meet diagnostic criteria. This patient does not meet the duration criterion and did not demonstrate prodromal symptoms, making brief psychotic disorder the most
appropriate diagnosis .
bducationa Objective : Brief psychotic disorder Is characterized by at least one acute psychotic symptom ( eg. delusions , hallucinations disorganized speech, disorganized behavior) lasting less than one month.
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38. A 29-year- old woman comes to the physician because of a 6-day history of rash, joint pain, and fatigue . Her temperature is 37.4 CC (99.4°F) , and blood pressure is 150/ 90 mm Hg . Physical examination shows a raised erythematous , blotchy malar rash and
,
mild peripheral edema . There is tenderness and swelling of several joints. Laboratory studies show:
Leukocyte count 3200/ mm3
Segmented neutrophils 62%
Eosinophils 3%
Lymphocytes 29 %
Monocytes 6%
Platelet count 74,000/ mm 3
Serum albumin 2.8 g/dL
Antinuclear antibody positive
Antibody to double- stranded DNA positive
Urine
Protein 3+
RBC casts 2+
Which of the following serologic studies is most likely to produce a false -positive result in this patient?
A ) Gold agglutinins
B ) Hepatitis B surface antigen
C ) Heterophile antibody
D ) p 24 antigen
E ) Rapid plasma reagin
Correct Answer E .
A rapid plasma reagin false positive result in this patient would be expected . This young woman with malar rash , arthritis , leukopenia: thrombocytopenia, positive antinuclear antibody (.ANA) , positive anti double -stranded DNA antibody ( anti- dsDNA ) . and an active
urine sediment meets criteria for a diagnosis of systemic lupus erythematosus (SLE) . Many patients with SLE also possess one or more antiphospholipid antibodies , including anticardioiipin antibody, lupus anticoagu ant , or anti-beta -2 -glycoprotein- 1 antibody
which predisposes to the development of venous or arterial thrombosis and recurrent pregnancy loss. Additionally, these antibodies are known to interfere with the rapid plasma reagin (RPR ) test for syphilis. The RPR tests for the presence of antibodies against a
cardiolipin-cholesterol-lecithin antigen , which are called reagin antibodies In patients who possess an anti-cardiaEipin antibody the RPR will be falsely positive . Follow up tests to evaluate for infection with syphi is should involve a treponemal test such as
,
Treponema pallidum particle agglutination assay ( TPA) or fluorescent treponemal antibody absorption (FTA -ABS ) test.
Incorrect Answers : A, B . C . and D.
Cold agglutinins ( Choice A ) are circulating IgM antibodies against erythrocyte antigens that , upon binding to the erythrocyte antigen , cause agglutination and extravascular hemolysis. These antibodies are active at colder temperature, so agglutination occurs
primarily in the extremities . This is a rare cause of autoimmune hemolytic anemia in patients with SLE .
Hepatitis B surface antigen (HBsAg) ( Choice B) may persist for several weeks after hepatitis B vaccination, but a false positive HBsAg would not be expected in SLE .
Heterophile antibodies (Choice C ) are antibodies that react to antigens from unrelated species such as sheep or horse erythrocyte antigens . The heterophife antibody test is commonly used to diagnose mononucleosis from Epstein-Barr virus . While false positive
tests have been reported in patients with SLE , they are far less common than a false positive RPR .
p 24 antigen ( Choice D ) is found on the surface of HIV and is a component of the screening test for HtV. False positive results are known to occur and should be followed up with confirmatory testing typically with an HIV- 1/ 2 antibody differentiation assay and/or
,
HIV RNA level.
Educational Objective: Patients with SLE also commonty have antiphospholipid antibodies The RPR test for syphilis evaluates for the presence of antibodies against specific syphilis antioens to which anticardioiipin antibodies react resulting in a false positive
,
RPR.
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39. A 20-year- old man is brought to the physician because of a 4- hour history of abdominal pain nausea and vomiting . He says that he had been drinking ethanol heavily all weekend , and he took three doses of acetaminophen within 2 hours after the onset of
; ,
a severe headache Monday morning This patient is at increased risk for liver injury because of which of the following actions of ethanof ?
A ) Activation of IgE- mediated mast cell degranulation

B ) Decreased acetaminophen clearance via glucuronidation
C ) Increased btoavai I ability of acetaminophen
D ) Induction of cytochrome P 450 enzymes that activate acetaminophen to a hepatotoxic metabolite
E ) Metabolic acidosis due to an increased NADH : NAD + ratio
Acetaminophen poisoning is more common in patients with underlying risk factors , including exposure to alcohof and hepatotoxic drugs . When taken at therapeutic doses , acetaminophen is safely metabolized through phase II conjugations , including glucuronidation
and sulfation . In the setting of acetaminophen overdose , saturation of phase II metabolic pathways leads to excess acetaminophen metabolized by CYP-mediated reactions to M-acetyl-p- benzoquinoneimme (NAPQI } , which has strong oxidizing properties and is
directly hepatotoxic . Chronic alcohol use increases the risk for hepatotoxicity in patients who take high doses of acetaminophen . Ethanof leads to the induction of P 450 enzymes that result in the increased production of NAPQI when high doses of acetaminophen
are ingested . The antioxidant molecule glutathione conjugates NAPQI , allowing it to be safely excreted and depletion of glutathione is a hallmark of acetaminophen toxicity. Acetaminophen toxicity is treated by repleting hepatic stares of glutathione through
,
intravenous or oral administration of N- acetylcysteine .

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Activation of IgE- mediated mast cell degranulation ( Choice A ) is the mechanism of action of type hypersensitivity reactions and underlies many allergic reactions . Alcohol does not increase hepatic sensitivity to acetaminophen through an allergic mechanism .
Decreased acetaminophen clearance via glucuronidation ( Choice B) does not occur as a result of alcohof exposure . Rather than affecting the capacity of the liver to perform glucuronidation reactions alcohol increases the capacity of the liver to produce NAPQI
through the induction of P450 enzymes .
Increased bioavailability of acetaminophen ( Choice C) does not occur. Acetaminophen has high oral bioavailability , which is not altered by the ingestion of alcohol
Metabolic acidosis due to an increased NADH: NAD + ratio ( Choice E ) may occur as a result of alcohol ingestion but does not impact the metabolism of acetaminophen . The metabolism of ethanol to acetaldehyde by alcohol dehydrogenase converts NAD + to NADH
leading to decreased NAD + and increased NADH . Because of the LeChatelier principle , the excess NADH is responsible for an increased activity of numerous metabaEic pathways that utilize NADH as a cofactor, including the production of lactic acid and the
inhibition of allosteric enzymes within glycolysis and the tricarboxylic acid cycle. However decreased NAD + and increased NADH do not play a direct role in acetaminophen-mediated hepatotoxicity.
Educational Objective : Alcohol : eads to the induction of P 45 D enzymes that convert acetaminophen to /V-acetyl -p-benzoquinoneimine ( NAPQI) , a toxic metabolite that causes hepatotoxicity in the setting of acetaminophen overdose .
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40 . An 18-month- old boy has pinched , wrinkled facies and total loss of subcutaneous fat . He is alert. His height is at the 50th percentile and his weight is at the 2 nd percentile for his age . The fiver is not enlarged , and there is no edema. Which of the following is
the most likely diagnosis?
A ) Kwashiorkor
B ) Marasmus
C ) Pellagra
D ) Rickets
E ) Scurvy
Acute protein-energy malnutrition is characterized clinically by a decrease in mid-upper arm circumference weight for length, or body mass index . Unlike in chronic malnutrition , children maintain their linear growth because the weight is more quickly impacted than
,
the height . Acute malnutrition can be divided into two groups based on the presence or absence of edema . Marasmus , or wasting syndrome , occurs when the overall caloric intake is deficient, but no specific vitamins or minerals are missing . Wasting of muscle mass
and consumption of body fat stores is characteristic . It is not associated with edema. Affected children appear emaciated and weak and may be irritable . Autonomic functions may suffer, causing bradycardia, hypotension , and hypothermia . Redundant skin folds , as
seen in this case, arise because of loss of subcutaneous fat . in contrast , kwashiorkor is also a form of protein-energy malnutrition but is accompanied by edema . The edema begins in dependent areas but , with continued malnutrition , progresses to involve the
presacral . genitalia , and preorbital areas. Children with either marasmus or kwashiorkor malnutrition have compfications in nearly every organ system of the body including immune dysfunction, increased cortisol concentrations, decreased intestinal motility and
absorptive capacity and a tenuous fluid balance predisposing to acute heart failure.
,
Kwashiorkor ( Choice A } also known as edematous malnutrition is differentiated from marasmus by the presence of edema . Skin lesions and fatty liver, both absent in this case , are typically present in kwashiorkor.
, ,
Pellagra ( Choice C ) is caused by an acquired deficiency of niacin (nicotinic acid , vitamin Bg) . It is characterized by diarrhea , dementia, and dermatitis . Signs of protein -energy malnutrition are not present . Pellagra -like symptoms can also be seen in Hartnup disease
an autosomal recessive disorder caused by decreased gastrointestinal absorption of tryptophan , the precursor to nicotinic acid .
Rickets ( Choice D) , or childhood vitamin D deficiency, presents with multiple skeletal deformities including frontal bossing , nodules at the costochondral junctions of the anterior chest and delayed closure of the growth plates because of impaired bone
,
mineralization . Children may demonstrate bowing of the tibia and femur . Children will have hypoplastic teeth and multiple caries as mineralization of dentin is impaired . Vitamin D deficiency in children commonly comes from low exposure to UV radiation and low
dietary vitamin D intake (particularly from low vitamin 0 in breast milk ). Signs of protein- energy malnutrition are not present .
Deficiency in vitamin C leads to scurvy ( Choice E), which presents with signs and symptoms of impaired collagen synthesis including swollen , bleeding gums easy bruising and bleeding (eg . hemarthrosis ) , petechiae , impaired wound healing , and short fragile , curly
, ,
hair.
Educational Objective: Acute protein-energy malnutrition includes a non -edematous type (marasmus ) and an edematous type (kwashiorkor). Both are characterized clinically by wasting of muscle mass and consumption of body fat stores leading to emaciation .
Nearly every organ system of the body is affected by this severe malnourishment.
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41 . A 14-year- old boy is brought to the physician by his parents because of increasingly severe left knee pain during the past week . The pain is exacerbated by running or kneeling . He plays multiple sports and is currently in the middle of soccer season . There
has been no recent trauma to the area or related sports injuries . Physical examination shows full range of motion of both lower extremities . There is a discrete area of swelling just below the left patella over the proximal portion of the tibia . Palpation of the
area produces pain . Pain is also reproduced when he does a full squat . Examination of the right knee shows no abnormalities. Which of the following is the most likely cause of this patient' s condition?
A ) Chondromalacia
B ) Ligamental tear
C ) Osgood-Schlatter disease
D ) Osteochondritis
E ) Stress fracture
Osgood -Schlatter disease refers to osteochondrosis or traction apophysitis of the tibial tubercle that typically occurs in adolescent athletic children. Repetitive tension via the patellar tendon transmits to the tibia! tubercle , presenting as pain reported during activities
that increase the stress on the tubercle, such as kneeling, squatting, kicking or similar activities that increase the extensor force transmitted by the quadriceps . Patients localize pain to the anterior aspect of the proximal tibia and knee . Physical examination typically
,
discloses tenderness over an enlarged tibial tubercle The condition is diagnosed clinically; x-rays , if obtained , may show increased lucency in the area of the tibia] tubercle . Treatment is through rest , cryotherapy and non-steroidal anti-inflammatory medications , as
the condition resolves with time and unloading .
incorrect Answers : A . B : D , and E.
Chondromalacia ( Choice A ) as related to the knee refers to deterioration of cartilage along the posterior aspect of the patella . It is common in young athietes , especially runners , and presents with knee pain that is worse with bending . It can be differentiated from
Osgood-Schlatter disease by the location of pain , whereas chondromalacia wil not present with pain at the tibial tuberosity.
Ligamental tear (Choice B) is a broad term that in the context of the knee could describe damage to any of the collateral ligaments such as the anterior or posterior cruciate or the medial or lateral collateral ligaments . Tear or rupture of these ligaments presents with
,
pain which is worse when placing the affected ligament under strain , tenderness in the area of the injury, and laxity when evoking the motion restricted by the ligament itself.
Osteochondritis ( Choice D) describes the inflammation of bone or cartilage within a joint; it may also include the dissection of the cartilaginous layer away from adjacent bone . It is a cause of pain within, not adjacent to , a joint .
Stress fracture ( Choice E) is a repetitive use injury that results in microtrauma and small discontinuities in bone. Stress fractures are common in the lower extremities but would be less likely than Osgood -Schlatter disease to present with focal pain or tenderness
over the tibia ! tubercle .
Educational Objective: Apophysitis of the tibial tubercle , known as Osgood-Schlatter disease , is a common cause of knee pain at the insertion of the patellar tendon in young athletes . It presents with focal pain and tenderness that is worse with the application of
tension to the tibial tubercle .
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42 . A 40-year- old man is evaluated because his skin is extremely sensitive to sunlight . Exposure to the sun causes the formation of vesicles and blisters on the skin which frequently take weeks to heal . He is diagnosed with a disorder caused by the increased
,
synthesis of compounds in the skin that are subject to excitation by visible light Which of the following biochemical pathways is most likely defective in this patient?
A ) Bile acid synthesis

B ) Bilirubin degradation
C ) Heme synthesis
D ) Melanin synthesis
E ) Riboflavin metabolism
Porphyria cutanea tarda is characterized by severe cutaneous photosensitivity with blistering and hyperpigmentation after exposure to sunlight and is the most common of the porphyrias it is caused by decreased activity of uroporphyrinogen decarboxylase , an
,
enzyme used to in the production of heme . The initial substrates for heme are glycine and succinyl- CoA . Their conversion to heme begins in the mitochondria with a rate limiting step catalyzed by aminolevulinate synthase . A series of additional steps then occurs
which take place in the celtular cytoplasm in one of these intermediate steps uroporphyrinogen decarboxylase catalyzes the conversion of uroporphyrinogen ill to coproporphyrinogen HI . Not only will a deficiency in uroporphyrinogen decarboxylase prevent correct
, ,
heme synthesis , it will also cause uroporphyrinogen iil to accumulate . Accumulated uroporphyrinogen IN is then deposited in the skin. Upon exposure to light of wavelength 400nm , the molecule enters an excited state and releases photons which in turn create
reactive oxygen species within the skin . These reactive oxygen species damage the basement membrane , lipids and proteins nearby resulting in dermoepidermal separation and blister formation .
,
Incorrect Answers : A . B D . and E.

(
Bile acid synthesis ( Choice A ) uses cholesterol as the initial substrate . Cholesterol 7 a-hydroxylase is the rate -limiting step in the creation of bile acids. Porphyrins are not intermediate byproducts of this pathway. Impaired bile acid production will lead to decreased
intestinal absorption of lipids and fat- solubfe vitamins , but not photosensitivity and blister formation.
Bilirubin forms as a result of the degradation of heme. Bilirubin degradation ( Choice B) is the process by which bilirubin is first conjugated in the liver to become water soluble and then excreted into the gut via bile . If is then degraded by gut bacteria to urobilinogen.
Urobilinogen is either converted to stercobilin and excreted in the feces or is reabsorbed through the small intestine. If reabsorbed , 10 % is excreted by the kidneys as urobilin and 90% progresses to the liver where it is recycled . No enzyme deficiency in this pathway
causes porphyrins to accumulate .
Melanin synthesis ( Choice D) takes place in melanocytes , located in the basal layer of the epidermis Tyrosine is the initial substrate of melanin and tyrosinase catalyzes the rate limiiing step in patients with impaired melanin synthesis such as in oculocutaneous
, ,
albinism , photosensitivity is severe and blistering sunburns may form . However, this is not because compounds are being excited by visible light , but rather because there is no melanin to protect from the harmful effects of ultraviolet radiation on keratinocytes .
Impaired riboflavin, or vitamin B 2 metabolism ( Choice E) does not generate porphyrins . Metabolism of riboflavin creates FAD and FMN , two cofactors used in reduction- oxidation reactions such as the citric acid cycle . Riboflavin deficiency presents with lip and oral
l
commissure fissuring (cheilosis) and corneal vascularization .
Educational Objective: Porphyria cutanea tarda, the most common of the porphyrias is characterized by severe cutaneous photosensitivity with blistering and hyperpigmentation after exposure to sunlight . It is caused by a decreased activity of uroporphyrinogen
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decarboxylase , an enzyme used in the production of heme .
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43. A 70-year- old man with metastatic prostate cancer has been taking leuprciide for the past 3 months . Which of the following best describes this patient' s current serum luteinizing hormone ( LH ) and testosterone concentrations compared with concentrations
before treatment ?
LH Testosterone
A) T
B) T
C) No change T
D) no change
E) 1
Correct Answer : E
LeuproEide is a gonadotropin-releasing hormone ( GnRH) analog . If given in a pulsatile fashion, mimicking the physiologic secretion of GnRH it will act as a GnRH receptor agonist and increase follicle -stimulating hormone (FSH ) and luteinizing hormone (LH ) .
;
When leuprolide is initially started in a patient the hypothalamus reacts as if it were an agonist and there is a transient rise in LH and FSH for the first week of treatment . However, with continued use in a non-pulsatite fashion , as in this case, it will act as a GnRH
receptor antagonist and subsequently decrease FSH and LH. By decreasing the production of LH and the stimulation of Leydig cells leuprolide indirectly lowers testosterone. Prostate cancer is a hormonally sensitive cancer ; androgens play a critical role in its
,
growth . Thus by inhibiting testosterone production , this driver of cancer growth is removed , and sensitive tumors begin to shrink . This approach to treating prostate cancer is termed medical castration . Some tumors may become castration - resistant , in which
,
mutations develop that allow the cancer to continue growing without hormonal stimulation .
Incorrect Answers : A . B: C . and D.
While there is a transient increase in LH and testosterone ( Choice A ) for the first week of treatment , after three months of treatment leuprolide will be exerting GnRH antagonist effects. This will lead to decreased LH and testosterone concentrations .
Because LH stimulates the Leydig cells to produce testosterone , when LH concentration is decreased testosterone concentrations will also decrease { Choice B ). A medication which continuously increases testosterone would not be appropriate for use in prostate
,
cancer as it is an androgen-dependent malignancy and would continue to grow under androgen stimulation .
LH decreases rather than showing no change { Choice C ) when leuprolide is administered given its antagonistic effects on the GnRH receptors when given in a continuous fashion . Likewise , testosterone decreases rather than showing no change ( Choice 0 ) in
response to the decreased stimulation of the Leydig cetls .
Educational Objective : Leuprolide is used in prostate cancer as a form of medicaE castration . Administration of leuprolide in a continuous fashion decreases LH release by the pituitary and subsequently decreases the production of testosterone by the Leydig cells.
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44 . A 34 -year- old woman comes to the physician because of a 10-year history of constipation. She usually has fewer than three bowel movements weekly. She often has bloating and cramping , and she has to strain and apply perineal pressure to defecate . She
says that she does not have problems with sleep , appetite , or energy. Palpation of the abdomen produces diffuse discomfort ; bowel sounds are present . Which of the following is the most likely cause of this patient's gastrointestinal symptoms ?
A ) Colon polyps
B ) Congenital megacolon (Hirschsprung disease)
C ) Factitious disorder
D } Gluten enteropathy
E ) Irritable bowel syndrome
F ) Major depressive disorder
Correct Answer : E
Irritable bowel syndrome (IBS) is characterized by recurrent , intermittent abdominal pain and alteration of bowel habits as either a change in stool frequency or consistency. The abdominal pain may be either exacerbated or relieved by defecation and can vary
widely in location and character . IBS commonly presents with intermittent episodes of diarrhea and / or constipation , often which alternate. When diarrhea does occur it usually does so during waking hours which serves to differentiate it from other causes of
diarrhea . It is most common in middle -aged women and the pathogenesis is unknown . It is not caused by a structural abnormality, and physical examination will show nonspecific abdominal discomfort rather than localized pain Stress management may improve
bowel habits in patients with irritable bowel syndrome, which is often associated with concomitant anxiety. If medication is needed , dicyclomine is an antispasmodic and diphenoxylate slows gut motility. Both are used in the management of irritable bowel syndrome.
Incorrect Answers : A, B . C, D . and F.
Colon polyps ( Choice A ) present in a variety of subtypes , from non- neoplastic polyps (eg , hamartomatous , mucosal inflammatory, hyperplastic ) to potentially malignant polyps (adenomatous , serrated) . Polyps are typically asymptomatic and are only recognized
,
after screening colonoscopy. They are not a common cause of chronic constipation inflammatory polyps may be seen in inflammatory bowei disease , but not irritable bowel syndrome .
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Congenita! megacolon (Hirschsprung disease) ( Choice B) , or intestinal aganglionosis , is caused by the congenital absence of the distal portion of the myenteric plexus, a part of the enteric nervous system located between the inner and outer layers of the
musculahs externa. This often leads to a failure to pass stool within the first few days of life and constipation thereafter. An explosive expulsion of feces on rectal examination is a classic clinical finding . It does not present in adulthood .
In factitious disorder (Choice C). patients consciously produce symptoms (eg , purposely injuring themselves ) for primary gain . Primary gain is the motivation to be cared for which constitutes an unconscious motivator for the patient 's conscious production of
symptoms . This patient does not appear to be causing her constipation for primary gain .
Gluten enteropathy ( Choice D) , or Celiac disease , is an immunologic intolerance to the protein gliadin . Celiac disease typically presents with abdominal discomfort , bloating , nausea , and diarrhea , not constipation , following exposure to gluten, and may be
associated with weight loss and dermatitis herpetiformis .
Major depressive disorder ( Choice F) presents with depressed mood anhedonia, insomnia , weight loss , fatigue , impairments
, in concentration , guilt, psychomotor slowing , and suicidal ideation , none of which is patient is experiencing . Irritable bowel syndrome is
more likely to be seen in conjunction with anxiety than depression .
Educational Objective : Irritable bowel syndrome (IBS ) is characterized by recurrent , intermittent abdominal pain and alteration of bowel habits as either a change in stool frequency or consistency. The condition ; s chronic and in most patients the severity of
symptoms varies overtime .
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45. Human gene fragments in appropriate vectors may be introduced into bacterial cells by transformation . Which of the following is most likely to be used to transfer cloned human genetic material to bacteria ?
A ) DNAcomplexed with bacterial histones

B ) Human chromosomal fragments
C ) Naked DNA
D ) Purified euchromatin
E ) Purified heterochromatin
Transformation describes the ability of bacteria to uptake and Incorporate exogenous genetic material ( naked DNA ) from the environment . Following lysis of a cell DNA may exist extracellularly ; a bacterium may uptake such material through the cell membrane .
Transformation is one of three methods of horizontal gene transfer by which bacteria can acquire novei genes which may confer a survival benefit . Notab [ y Streptococcus pneumoniae and Haemophilus influenzae type B have demonstrated acquisition of genetic
;
material by transformation . In order for transformation to occur a bacterium must demonstrate competence (the ability to uptake such material ) . Competence occurs in states of stress such as starvation . Beyond transformation , horizontal gene transfer may also
occur via conjugation (in which two cells in direct contact typically involving a sex pilus ), exchange material, and transduction (transfer of genetic material via a viral vector such as a bacteriophage).
,
Incorrect Answers : A . B . D, and E.
DNA complexed with bacterial histones ( Choice A ) , human chromosomal fragments ( Choice B ) purified euchromatin ( Choice D): and purified heterochromatin ( Choice E) all describe fragments of DNA associated with additional protein complexes and of variable
;
sizes . The process of transformation requires naked DNA , which describes DNA that is not associated with proteins: liplds: or molecules that may shield it.
Educational Objective: Transformation describes the ability of bacteria to uptake and incorporate genetic material (naked DNA ) that is not associated with proteins or lipids from the environment . This mechanism may promote genetic diversity and acquisition of
survival advantage .
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46. A 4 -year- old girl has acute lymphoblastic leukemia that has not responded to aggressive treatment . The physician recommends palliative care to the parents and suggests that they talk to their daughter about her impending death and answer any questions
that she may have. The parents ask the physician to help them respond to her questions . When speaking with the child , the parents should anticipate that she will most likely understand death as which of the following?
A ) She will blame God for her illness and death

B ) She wifi comprehend that all living things die
C ) She will have no understanding of death
D ) She will view death as temporary and reversible
Most children between the ages of 3 and 5 years view death as temporary and reversible . Partly related to a lack of experience of death, they also do not understand that all living things inevitably die. Children of this age range who are dying may believe dying is a
punishment from their parents, signifying an inability to abstract . However these gaps in understanding can be filled by adults explaining death to children and by children's experiences of death . It is suggested that the parents of dying children help their child
understand the situation .
Incorrect Answers : A . B and C .

(
This patient is unlikely to blame God for her illness and death (Choice A) as it is too abstract a concept for a child this age. The patient is more likely to blame her parents . She may, depending on her parents ' religious beliefs , believe that death represents going to
Heaven without an abstract understanding of Heaven .
Starting at age five, children begin to understand that death is inevitable and irreversible ( Choice B ) . At this age: children may continue to demonstrate an incomplete understanding of death . Media images of death ( eg: ghosts ) may be part of this incomplete
understanding . At age fen. children typically understand that death is universal irreversible and renders people inanimate (versus believing in ghosts).
;
Only infants have no understanding of death ( Choice C ) . Toddlers typically begin to became aware of the concept of death over time.
Educational Objectives : Most children between the ages of 3 and 5 years view death as temporary and reversible. Further, preschool age children are frequently unaware of the inevitability of death .
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47. A 12 -year- old girl is brought to the emergency department 15 minutes after she accidentally siiced her left palm with a knife . Physical examination shows a 2- cm laceration over the left palm . The wound is cleansed and sutured . One week later the sutures
,
are removed . At this time , which of the following factors is most instrumental in the migration of fibroblasts into the area of wound healing?
A ) Collagen
B ) Fibronectin
C ) Heparin
D ) Immunoglobulin
E ) Plasminogen
Wound healing occurs via a staged process. In early wound healing , platelet aggregation and platelet plug formation occur to achieve hemostasis . In the subsequent 1 to 7 days , neutrophils and macrophages infiltrate the area and release growth factors and
cytokines that stimulate fibroblast proliferation . Fibronectin is essential for fibroblast migration by providing a pathway for migration during wound healing . Fibroblasts bind to peptide sequences within fibronectin , which guide them to the site of healing . Granulation
tissue forms as collagen is deposited into the area by fibroblasts and neovascularization begins to occur. During this time, wound edges contract from the action of myofibroblasts . Epidermal cells migrate across the newly deposited collagen matrix to reconstitute
normal skin appearance . In the following weeks and months , scar formation and remodeling occur via metalloproteinase- mediated collagen breakdown.
Incorrect Answers : A . C , D and E.

;
Collagen ( Choice A) is synthesized by fibroblasts and contributes to scar formation in the process of wound healing . Dermal collagen fibers increase as a result of scarring . While the majority of collagen fibers in healthy skin are type I collagen, scarring is initially
created by type III collagen .
Heparin ( Choice C) is a common anticoagulant that potentiates the action of antithrombin ill to inhibit multiple coagu ation factors. It does not relate to fibroblast migration in wound healing.
Immunoglobulins ( Choice D) are found on B lymphocyte membranes or are secreted into the serum by plasma cells to recognize antigens and activate the immune system in response to a pathogen .
Plasminogen ( Choice E ) is converted to plasmin, which subsequently degrades fibrin clots leading to clot dissoiution . Plasminogen is made in the liver and its role is to degrade and prevent clot formation, not guide fibroblasts.
Educational Objective: Fibronectin is essential for fibroblast migration and provides a pathway for migration during wound healing . Fibroblasts bind to peptide sequences within fibronectin , which guide them to the site of healing.
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48. The focal health department is investigating an outbreak of acute hepatitis A in two city districts by reviewing the medical records at a health center in each district. The investigators pfan to analyze the clinical and epidemiologic characteristics of patients
who tested positive for hepatitis A serum laM antibody compared with characteristics of those who tested negative for the antibody. Which of the following best describes this study design?
A ) Case series
B ) Case- control study
C ) Prospective study
D } Randomized trial
E ) Retrospective cohort
This study compares one group of patients with an outcome under study (seropositive for Hepatitis A IgIM antibody ) ( cases) against a second matched group without that outcome (controfs ) and identifies the associated exposure within each group . This study design
is known as a case-control study. Case-control studies can be conducted in a prospective or retrospective manner but are always observational studies . By grouping patients by outcome and comparing differences in the odds of exposure . case -confrol studies can
detect associations between exposure and outcome, such as exposure to certain risk factors and outcome of contracting hepatitis A as in this study. This is described statistically as an odds ratio (OR ). Two unrelated variables will have an OR of 1.0 , whereas
positive association between an exposure and an outcome will have an OR greater than 1.0 and negatively associated variables will have an OR less than 1 0 . Case-control studies are therefore capable of establishing association between exposure and outcome,
but they do not establish causality.
Incorrect Answers : A . C, D, and E.
A case series study ( Choice A) is a descriptive study that describes the history, possible exposures and clinical findings of a group of patients with a similar diagnosis. Case series are non- analytic studies . They do not test a hypothesis and do not generally contain
,
a control group.
A prospective study ( Choice C) is one in which one group of patients experiences an intervention or exposure and an associated control group does not. The two groups are followed and the desired outcome tracked . A randomized trial ( Choice D ) is a stringent type
of prospective study wherein patients are randomly assigned to receive a particular intervention . The intervention may be compared against placebo therapy or against standard therapy, depending on the study design . When combined with blinding procedures,
prospective randomized control studies form the standard for medical research and generate strong evidence as compared to observational or descriptive studies .
,
Retrospective cohort studies ( Choice E ) examine a group of patients with a known exposure and determine the risk for developing a given disease outcome within the exposed group compared to a control group lacking the known exposure . Cohort studies may be
prospective or retrospective. Cohort studies differ from case -control studies in that patients are grouped according to exposure status in the former design and are grouped according to disease outcome status in the latter design . Cohort studies calculate relative
risk (RR ).
Educational Objective : Case -control studies group patients according to disease outcome status and analyze the odds of exposure to a particular hazard . The appropriate statistica measure of case- control studies is the odds ratio (OR).
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49. A 1 -day-old female newborn with aniridia undergoes genetic testing . Her father and several other paternal family members also have aniridia . Chromosomal microarray analysis of the patient shows no gain or loss of gene dosage throughout the genome :
including the chromosome 11p 15 region that contains the PAX6 commonly mutated in patients with aniridia. Routine chromosomal analysis shows a balanced translocation between chromosomes 1 and 11 with the chromosomal breakpoint on
chromosome 11 being 11p 15 . The same balanced translocation is also found in all of the affected family members but not in the unaffected family members . However DNA sequencing of the PAX6 located at 11p15 shows no mutation in any of the exons of
PAX6 in the patient Which of the following is the most likely cause of this patient' s condition ?
A ) Creation of a new stop codon

B ) Deletion of an intron
C ) Disruption of a regulatory sequence
D ) Skipping of an exon
E ) Transition of a base
Balanced translocations occur when a segment of a chromosome has switched places with another broken chromosomal segment . In this patient scenario: a segment of chromosome 1 has been relocated and joined onto chromosome 15 just as a segment of
chromosome 15 has been joined onto chromosome 1 in place of the translocated segment . Frequently, chromosomal translocations carry no significant consequence unless the break point affects a regulatory sequence or section of an exon that results in reduced
or absent translation of the encoded protein fn this case: chromosomal analysis showed that the exons of PAX6 , a highly conserved gene that encodes the iris demonstrated no mutations . Therefore, the translocation must affect a promoter enhancer silencer or
,
;
similar regulatory sequence that prevents appropriate expression of the gene itseff . Aniridia is an autosomal dominant mutation: homozygosity at this gene locus is often severe and fatal. This patient inherited one copy of the abnormal chromosome from her father
and a normal copy from the mother leading to the observed phenotype. Regulatory sequences in DNA include promoters, the sites bound by RNA polymerase and transcription factors . enhancers: sites bound by transcription factors that generally upregulate
transcription , and silencers , regions bound by repressor proteins.
Incorrect Answers : A, B . D, and E.
Creation of a new stop codon ( Choice A) would result in cessation of ribosoma! translation of the protein prior to completion . A stop codon mutation would likely be detected in the chromosomal analysis of the patient' s PAX6 gene , which was reportedly found to be
without mutation.
Deletion of an intron (Choice B) would generally have no effect on the phenotype, as introns are non-translated intervening regions of DNA between exons that are spiiced out during pre -messenger RNA processing .
Skipping of an exon ( Choice D ) would result in the synthesis of an incomplete or misfolded protein, lacking peptides encoded by the skipped exon . In the case of a translocation, from the point of translocation and downstream , the translated protein would differ
entirely from the protein produced as an alternate gene would be translated instead based on the regulatory elements governing the transposed segment
Transition of a base ( Choice E) defines a type of point mutation where a like- kind mutation occurs within a nucleotide (eg , purine for purine, pyrimidine for pyrimidine ) . Point mutations can be silent (the new nucleotide codes for the same base) , missense (the
nucleotide codes for an alternate and sometimes chemically different base), or nonsense (the point mutation generates an early stop codon). Transition mutations occur within a DNA sequence .
Educational Objective: Translocation may result in failure to transcribe RNA because of disruption of a regulatory element (eg , promoter) within a gene . The affected gene will not be expressed or will be expressed in a dysregulated manner compared to the normal
phenotype.
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50 The graph shows the mean steady state pfasma concentration of Drug X as a function of time in a subject who has normal weight ( solid curve) and a subject who is obese ( dashed curve) . Both subjects take
10 mg of Drug X daily. Which of the following best describes the disposition of Drug X In the obese patient compared with the patient who has normal weight ? x
m
A ) Greater volume of distribution
cti
B ) Higher clearance £
»
C ) Lower bioavailability
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D ) Slower absorption rate

E ) Shorter half-life i
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r
7
Time (days)
Volume of distribution Is the theoretical volume in which a drug exists given its piasma concentration following a dose of medication There are three main compartments into which a medication can distribute : the intravascular compartment the interstitial
,
compartment , and the intracellular compartment ( including fat) . With an increased volume of distribution , the same dose of medication will lead to a smaller plasma concentration (ie it will distribute more widely into tissue) , and it will take longer for the medication
;
to reach a steady state within the plasma . Large molecules or protein - bound molecules generally remain within the vasculature and quickly reach a steady state concentration given the relatively low volume of the intravascular compartment . Smaller hydrophilic
molecules tend to move info the interstitial space , which increases their volume of distribution and increases the amount of time if takes for the medication to reach a steady state concentration. Small lipophilic mofecules , however exhibit the largest volume of
distribution as they are commonly taken up by adipocytes which greatly increases the volume in which they are distributed . Therefore , it takes these molecules longer to reach a steady state concentration , especially in obese patients in which the volume of
,
distribution is even greater given the presence of increased fat stores , as seen in this graph.
Incorrect Answers : B, C , D, and E.
Higher clearance ( Choice B) of a medication indicates that more medication is removed from the body in a given period of time. Differences in clearance are typically because of changes in hepatic or renal function and are commonly displayed in a graph that
shows the decline in drug concentration . An increase in clearance with the same volume of distribution would require a higher maintenance dose to reach steady state .
Lower bioavailabifity (Choice C ) is described as a decreased absorption of the medication lowering the amount of medication that is available to act in the body . It commonly refers to oral medications , as they are subject to first pass metabolism in the liver.
,
Bioavailability is not subject to alterations based on body fat percentage , and a decrease in bioavailability would require an increase in maintenance dosing to reach a similar steady state concentration .
Slower absorption rate ( Choice D) in the setting of similar volumes of distribution and clearance would result in an increased time to reach steady state concentration . However, the absorption rate of oral medications is not typically affected by body weight .
Shorter half-life ( Choice E ) is a decrease in the amount of time that it requires for a drug ' s concentration in plasma to decrease by 50% . Half-life is indirectly related to clearance , such that it decreases with increases in plasma clearance . Conversely, it is directly
proportional to the volume of distribution. A decreased half-life would decrease the time necessary for the medication to reach steady state concentration , unlike this scenario .
Educational Objective : The volume of distribution is the theoretical volume in which a drug exists based on its piasma concentration . It is altered by changes in volume of the intravascular, interstitial , and intracellular compartments. Increases in volume of
distribution are exhibited by a slower rate of increase in plasma drug concentration and a prolonged period before reaching steady state concentration.
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1 . The graph shows the rate of breakdown of skeletal muscle glycogen by phosphorylase in the presence and absence of AMP Based on the data which of the following best describes the action of AMP?
,
vmax
o + AMP
A ) Allosteric activator No effector
OJ
B ) Allosteric inhibitor E
TO
!4 Vmax
LZ
C ) Catabolite activator
D ) Catabolite repressor
1^ 1
E } Covalent modifier of the enzyme
F ) Covalent modifier of phosphorylase kinase
Correct A ns wer A .
1
Enzymes are kineticaily categorized by their Michaelis constant , Km . which inversely reflects their affinity for their substrate , and by Vmax the maximum catalysis rate of the enzyme . In other words , as Km, decreases, affinity for the substrate increases . Km is
;
defined as the substrate concentration at which the enzyme reaches one-half of its Vm a x - In this case , the kinetic analysis of the patient' s glycogen phosphorylase shows that the concentration of substrate [Si at one -half of Vmax decreases in the presence of AMP.
Therefore , AMP must increase the affinity of the enzyme for its substrate, a phenomenon that classically results from a conformational change in the active site of the enzyme where substrate binds . Allosteric activators influence enzymes in exactly this manner -
inducing conformational change at the active site which in turn increases binding affinity for the substrate. This is reflected by the decreased Km . AMP, a breakdown product of adenosine triphosphate (ATP), is generated in states of fasting Glycogen a storage ,
form of glucose in liver and muscle, is broken dowfn by glycogen phosphorylase to liberate free glucose molecules when glucose is depleted in fasting. AMP, when present in excess , signals a state of fasting . ] t upregulates glycogen degradation through glycogen
phosphorylase by acting as an allosteric activator of the enzyme.
Incorrect Answers : B , C , D , E . and F.
Allosteric inhibitors ( Choice B) modify enzymes in a manner that their affinity for their target substrate is reduced at the active site, not increased . Allosteric inhibitors would be reflected in enzyme kinetic anaiysis by an increase in the Km indicating that a greater
concentration of substrate would be required to elicit the same binding .
Catabolite activator ( Choice C ) and catabolite repressor ( Choice D ) describe phenomena in which transcription of genes is affected ; this was first described in the lac operon . When given the option between using glucose or lactose as a substrate , glucose was
preferred , and synthesis of enzymes related to lactose metabolism was repressed . By contrast , in an absence of glucose, synthesis of lactose-metabolizing enzymes was promoted .
Covalent modifier of the enzyme ( Choice E ) and covalent modifier of phosphorylase kinase ( Choice F) suggest modification of the enzyme by phosphorylation or dephosphorylation . Covalent modification can affect conformation at the active site however AMP is,
not acting as a phosphate donor or recipient in this case; it binds directly to induce conformational change .
Educational Objective: Allosteric activators influence enzymes by inducing conformational change at the active site which increases binding affinity for the substrate. This is reflected by a decreased Km . AMP a breakdown product of adenosine triphosphate , is
,
generated in states of fasting and thus upregulates glycogen phosphorylase to liberate stored glucose and supply the cells with a substrate for glycolysis when none is nutritionally available.
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2 . A 22 -year- old man is brought to the physician because of a 1 -week history of bleeding gums and bruising of his legs and a 3 -month history of weakness and fatigue. His temperature is 37°C (&S.6T). Physical examination shows pallor boggy gingival
hypertrophy, and several petechial lesions and ecchymoses scattered over the lower extremities. The spleen tip is palpated 3 cm below the left costal margin. Laboratory studies show:
Hemoglobin 8.2 g/dL
Hematocrit 24%
Leukocyte count 32.000/ mm 3
Platelet count 23,000/ mm 3
Microscopic examination of a peripheral blood smear shows 42% blast forms. Which of the following is the most likely diagnosis ?
A ) Acute lymphocytic leukemia

B ) Acute myelogenous leukemia
C ) Chronic lymphocytic leukemia
D ) Chronic myelogenous leukemia
E ) Hairy ceil leukemia
Acute myelogenous leukemia (AML) is the most likely diagnosis in this patient with pancytopenia, gingival hypertrophy, and 42% blasts on peripheral smear. AML is a neoplasm arising from cells within the myeloid lineage , which is distinct from the lymphoid lineage .
There are myriad mutations that can be present in malignant myeloid cells and the types of mutations confer different risk profiles . Patients with poor risk mutations undergo stem cell transplant if they are able to achieve remission after induction and consolidation
chemotherapy with cytarabine and idarubicin . Common presenting symptoms include fatigue , malaise , fevers , and weight oss. Gingival hypertrophy is commonly seen in a particular subtype of AML known as acute promyelocytic leukemia and is a result of
infiltration of the gums with malignant cells Leukemia cutis , a rash that represents infiltration of the skin by malignant cells, can also occasionally be seen . Other fmdings include petechiae or purpura from thrombocytopenia and anemia from diffuse marrow
infiltration by blasts . Induction therapy for AML is considered urgent and is usually done with cytarabine and idarubicin , which is followed by consolidation therapy . Patients with poor risk mutations invariably go on to stem cell transplant if they can achieve remission
initially.
Incorrect Answers : A, C , D , and E.
Acute lymphocytic leukemia (ALL ) ( Choice A) is primarily a malignancy of childhood but is occasionally seen in adults . Cytopenias are common and peripheral smear also shows blasts as in this patient , although these blasts wil be of the lymphoid lineage and
appear different from myeloid cells. Gingival hypertrophy is not generally associated with ALL .
Chronic lymphocytic leukemia ( Choice C ) is a malignancy of mature, differentiated B lymphocytes . Common findings include lymphocytosis , and peripheral smear classically shows numerous lymphocytes with large blue nuclei and scant cytoplasm, many of which
may appear ruptured. Blasts are not seen on peripheral smear as the malignant cells are mature. Treatment with ibrutinib is initiated if patients have profound cytopenias or disabling symptoms such as malaise and buiky lymphadenopafhy.
Chronic myelogenous leukemia (Choice D) is defined by the presence of the Philadelphia (Ph) chromosome , which is created by a translocation between chromosomes 9 and 22 resulting in constitutive activation of the ABL 1 tyrosine kinase . Peripheral smear will
show a diverse set of immature or partially mature cells of the granulocytic cell iineage with basophilia.
Hairy cell leukemia (Choice E) is typically a disease of older adults and is diagnosed in the setting of pancytopenia , lymphocytes with cytoplasmic projections on peripheral smear , and positive tartrate resistant acid phosphatase ( TRAP ) . Malaise , abdominal
distention, early satiety, and pain from splenomegaly are common presenting complaints . Treatment is reserved for symptomatic patients .
Educational Objective : AML is an aggressive malignancy of myeloid cells and commoniy presents in adults with pancytopenia and circulating blasts on peripheral smear. Gingival hypertrophy is not an uncommon finding and represents infiltration of the gingiva by
malignant cells . Depending upon the types of mutations present , patients are divided into good , intermediate or poor risk subcategories . Those with poor risk disease invariably go on to stem ceil transplant after induction and consolidation chemotherapy.
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3 . A 3-month -old girl is brought to the physician by her mother for a welF- child examination . Her mother says that the infant can lift her head when lying prone. The patient is eating well and recently started sleeping about 6 uninterrupted hours through the night.
The mother adds that the baby does not yet smile in response to human faces and has not started to coo or gurgle with attention . The patient is at the 25th percentile for length and weight and 10th percentile for head circumference. Physical examination
shows no other abnormalities . Which of the following best describes this infant' s development?
Motor Social Verbal and Cognitive

A) Normal normal normal
B) Normal normal delayed
C) Normal delayed normal
D) Normal delayed delayed
E) Delayed normal normal
F) Delayed normal delayed
G) Delayed delayed normal
H) Delayed delayed delayed
In the first 3 months of life infants are expected to demonstrate the gross motor skills ot holding their head up and pushing their body up with their arms when lying prone. Expected fine motor skills include grasping and shaking toys and bringing their hands to
,
their mouth . Most 3-month-olds demonstrate a social smile. Verbally, 3-month- old infants are expected to coo , babble, and imitate vowel sounds. This patient does not meet social or verbal/cognitive milestones . Screening for developmental delays alerts
physicians to the potential need for further medical evaluation and/or early referral to developmental specialists. Early intervention has been demonstrated to improve outcomes.
Incorrect Answers: A . 6 . C, E. F, G, and H .
This patient , who does not smile or coo yet, does not meet the social or verbal /cognitive milestones f o r a 3-month- old infant (Choices A. B , C. E, F, G. and H). This baby should be further evaluated for causes of developmental delay.
Educational Objective: By age 3 months infants are typically able to hold their head up , grasp toys smile socially and babble or coo.
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4 . A 34 -year- ofd woman comes to the physician because of a 2-week history of easy fatigability. She is pale . Physical examination shows scleral icterus and mild jaundice. Laboratory studies show :
Hemoglobin 9.2 gWJL
Reticulocyte count 10% of red cells
Serum
Total bilirubin 3.0 mg/dL
Direct bilirubin 0.3 mg/dL
Which of the following is most likely responsible for the development of anemia in this patient?
A ) Chronic disease
8 ) Hemoglobinopathy
C ) Hemolysis
D ) Hypersplenism
E ) Ineffective erythropoiesis
Autoimmune hemolysis explains this patient ' s anemia unconjugated hyperbilirubinemia , and reticulocyte sis. Autoimmune hemolytic anemia (AIHA ) occurs because of production of antibodies targeting circulating red blood cell (RBC ) surface antigens , marking them
,
for removal in the reticuloendothelial system ( RES ) or fixing complement leading to intravascular hemolysis . IgG antibodies are active at the physiologic temperature of the human body (called warm AIHA ) ; these do not routinely activate complement instead they
,
mark the cells for removal . Phagocytosis of the IgG antibody along with a component of the erythrocyte membrane creates sphere- shaped RBCs seen on peripheral smear In contrast . IgM antibodies bind and fix complement at lower temperatures and result in
intravascular hemolysis (called cold AIHA) . IgG antibodies are known as warm antibodies : and IgM antibodies are known as cold antibodies . Regardless of the type of antibody laboratory findings show normo- or microcytic anemia an increased reticulocyte count
, ,
consistent with increased hematopoiesis , and unconjugated hyperbilirubinemia from hemoglobin released from lysed erythrocytes . Diagnosis is made by laboratory analysis , a compatible clinical history, and positive direct antibody test (DAT, Coombs) . In the DAT.
the patients erythrocytes are washed free of plasma and Incubated with Coombs reagent an anti- IgG and anti- complement antibody If an autoantibody or complement is bound to the surface of the erythrocytes , the Coombs reagent will bind to it and cause
, ,
agglutinaLom
Incorrect Answers : A . 8 , D . and E.
Chronic disease ( Choice A ) such as chronic infection or autoimmune disease can cause anemia . The mechanism involves increased hepcidin concentrations that decrease iron absorption and increase iron storage in the bone marrow, preventing use of iron by
erythrocyte precursors , thereby resulting in anemia . As hematopoiesis is ineffective, the reticulocyte count will be decreased . Increased bilirubin is not consistent with this diagnosis .
Hemoglobinopathy ( Choice B) describes numerous conditions including the thalassemia and sickle cell disease among others . These conditions cause anemia because of deficient production of normal adult hemoglobin or production of abnormal hemoglobin.
Retieulocytosis and increased bilirubin concentrations can be seen if hemolysis is present , but these conditions are chronic and present at birth.
Hypersplenism ( Choice D) can result from infection , myeloproliferative neoplasms , or cirrhosis with portal hypertension . Erythrocytes passing through an enlarged spleen may have slower transit times and may be removed prematurely from the circulation , but
hypersplenism does not cause hemolysis or manifest with an increased bilirubin .
Ineffective erythropoiesis ( Choice E) is a feature of many diseases including iron deficiency anemia , anemia of chronic disease , and bone marrow malignancies. Patients with these conditions demonstrate a low reticulocyte count .
Educational Objective : AIHA results from the binding of an autoanfibody to RBC surface antigens , leading to removal via the RES or to intravascular hemolysis . Diagnosis is made by a positive DAT unconjugated hyperbilirubinemia, and reticulocytes on the
peripheral smear.
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5 . A GG -year- old man is brought to the emergency department 30 minutes after the sudden onset of substernal chest pain that radiates to the neck and left arm; the pain is associated with weakness , nausea, and profuse sweating . He was jogging during the
onset of pain He has a 5 -year history of hypertension treated with Indapamide. His pulse is 90/ min , and blood pressure is 150/90 mm Hg. Cardiac examination shows an S 4. Treatment with sublingual nitroglycerin resolves his pain within 2 minutes . An EGG
shows a 2 -mm ST-segment elevation in the anterior leads . Treatment with a fibrinolytic drug is beneficial to this patient because of which of the following mechanisms of action?
A ) Catalyzing the formation of plasmin

B ) Catalyzing the platelet llb/llla receptor complex
C ) Inhibition o!ADP-induced platelet-fibrinogen binding
D ) Inhibition of conversion of fibrinogen to fibrin
E ) Inhibition of the synthesis of thromboxane A 2
F ) Inhibition of vitamin K -dependent coagulation factor synthesis
Correct Answer: A .
Myocardial infarction classically presents with acute- onset chest pain, often radiating to the neck , jaw, or arm, along with shortness of breath, nausea , and/or lightheadedness. Risk factors include a history of smoking , diabetes metlitus, hypertension, hyperlipidemia ,
and/ or obesity. If the nfarction results in left ventricular dysfunction patients may experience cardiogenic pulmonary edema resulting in shortness of breath tachypnea , hypoxia , audible rales, and S 3 o r S 4 gallops. Diagnosis is made using clinical history, analysis of
, ,
cardiac biomarkers , and an ECG, which may show ST- segment elevation or depression , inverted T- waves , or Q- waves. Treatment requires the use of antiplatelet agents (eg , aspirin , clopidogref) plus anticoagulants ( eg. heparin) , pain control and revascularization
,
through angioplasty, thrombolysis , or coronary artery bypass grafting . For patients who cannot receive percutaneous coronary intervention in a timely manner , thrombolytics are indicated . Thrombolytics such as tissue plasminogen activator function by catalyzing the
formation of plasmin from plasminogen . Plasmin is a serine protease that cleaves fibrin dots .
Incorrect Answers : B , C , D , E . and F.
Catalyzing the platelet llb/ llla receptor complex ( Choice B ) is not the mechanism of action of thrombolytics . The platelet llb/ llla receptor binds to fibrinogen during the process of platelet aggregation . Inhibition of ADP-induced platelet -fibrinogen binding ( Choice C)
occurs with ADR receptor blockers (eg , cfopidogreE) that inhibit expression of the llb/il la receptor and with monoclonal antibodies ( eg. abciximab ) that directly bind the receptor.
Inhibition of conversion of fibrinogen to fibrin ( Choice D) is the mechanism of heparin anticoagulants and direct thrombin inhibitors such as lepirudin and bivalfrudin . Thrombin catalyzes the conversion of fibrinogen to insoluble fibrin polymers for clot formation .
Heparin increases the binding affinity of antithrombin 111 , which inactivates thrombin . Direct thrombin inhibitors directly inhibit thrombin activity.
Inhibition of the synthesis of thromboxane A 2 ( Choice E ) occurs with cyclooxygenase inhibitors such as aspirin, which prevent the conversion of arachidonic acid to thromboxane A 2. Thromboxane A 2 is involved in platelet activation and its decreased synthesis
,
results in diminished platelet activity.
Inhibition of vitamin K-dependent coagulation factor synthesis ( Choice F) occurs with warfarin because of the inhibition of vitamin K epoxide reductase. This enzyme is necessary for recycling vitamin K . an essential cofactor in the synthesis of coagulation factors in
the liver.
Educational Objective: Myocardial infarction carries a high risk for morbidity and mortality. It is most commonly caused by atherosclerotic plague rupture in the coronary arteries with thrombosis formation . Antithrombotic agents are a mainstay of therapy . For patients
who cannot receive percutaneous coronary intervention or coronary artery bypass grafting in a timely manner, thrombolytics are indicated .
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6 . A 70-year- old woman comes to the physician for a routine pelvic examination . During speculum examination of the vagina and cervix the Valsalva maneuver causes a bulge of the anterior vaginal wall . Which of the following is the most likely cause of this
,
finding?
A ) Bartholin gland cyst

B ) Cystocele
C ) Obturator hernia
D ) Rectocele
E ) Uterine prolapse
Normal pelvic support is caused by the action of several pelvic muscles and ligaments of the pelvic floor, including the levator muscles: urogenital diaphragm perineal body endopelvic fascia , uterosacral and cardinal: ligaments , anal sphincter and urethral sphincter.
, , ,
Defects in this pelvic support may result in urogenital pro apse : which is caused by the loss of connective tissue and muscular support of the uterus, paravaginal tissue , bladder wall , urethra , or distal rectum . Risk factors for pelvic support defects include collagen
and connective tissue disorders , previous vaginal delivery, menopause prior pelvic surgery, and increased intra- abdominal pressure (eg , obesity and chronic constipation) . Signs and symptoms include a vaginal mass , vaginal pressure, perineal discomfort , and
,
urinary or fecal retention or incontinence. In the case of a cystocele , the bladder prolapses into the anterior vaginal wall. It is associated with stress urinary incontinence as well as urinary retention . Physical examination will show a bulge of the anterior vaginal wall ,
,
as in this patient . Management for a symptomatic cystocele may include the insertion of a vaginal pessary which is a mechanical device that provides pelvic support along with pelvic floor exercises or surgical correction .
, ,
A Bartholin gland cyst ( Choice A) appears as a swollen, fluctuant mass at the posterior labium majora caused by obstruction of Bartholin gland outflow. If left untreated , a cyst can progress to an abscess, with the development of erythema and tenderness to
palpation . It does not cause a mass on the anterior vaginal wall.
An obturator hernia ( Choice C ) is a herniation of the abdominal contents through the obturator foramen , along with the obturator vessels and nerve . It presents with abdominal pain and a potentially palpable mass in the groin . It is more common in patients with
increased intra -abdominal pressure , as well as elderly multiparous women .
,
A rectocele ( Choice D) is caused by weakness of the pelvic floor, with the rectum prolapsing into the posterior wall of the vagina , rather than the anterior wal as in this patient . Symptoms include constipation and a palpable bulge of the posterior vaginal wait .
Uterine prolapse ( Choice E) is related to pelvic floor weakness and presents with prolapse of the uterus into the vaginal canal This would be seen on speculum examination with lowering of the cervix toward the vaginal opening with a Valsalva maneuver, rather
than an anterior vaginal wall bulge .
Educational Objective: A cystocele is a form of pelvic organ prolapse caused by weakness of the pelvic floor musculature, commonly occurring in the setting of connective tissue disorders , previous vaginal delivery, menopause, prior pelvic surgery and increased
,
intra-abdominal pressure . A cystocele presents most commonly with urinary retention or incontinence and an anterior vaginal wail bulge on physical examination .
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7 . A 12 -year- old boy with seizure disorder is brought to the physician by his parents for a follow -up examination. His mother has two neurofibromas , and his brother and maternal uncle each have numerous cafe au lait 0-1-0
I 2
spots . Physical examination shows numerous flat, irregular pigmented skin lesions. He is individual IV-2 in the pedigree shown . Which of the following is the most likely pattern of inheritance of this family's disorder ?
A ) Autosomal dominant with variable expressivity

ii O
B ) Autosomal dominant with variable penetrance
C ) Autosomal recessive with high heterozygote frequency
in 6 2 3
D ) Autosomal recessive with low heterozygote frequency IV O B B

E } X -linked dominant
F ) X-linked recessive
1
s 2 3
O Unaffected female
Unaffected male
# Affected female
Affected male
Corned Answer: A .
Neurofibromatosis 1 is an autosomal dominant neurocutaneous disorder that typically results from an inherited mutation of the NF1 tumor suppressor gene on chromosome 17. Neurofibromatosis 1 is inherited with complete penetrance and variable expressivity ,
signifying that all family members who inherit the mutation manifest the disease but may demonstrate different phenotypic presentations. Rarely, the mutation in the NF1 gene will occur sporadically instead. The disorder presents with cutaneous neurofibromas
(benign neoplasms derived from neural crest cells) , cafe au lait spots (flat , irregular pigmented lesions ) , pigmented iris hamartomas (Lisch nodules ), optic gliomas (which may lead to seizures) , and/ or pheochromocytomas . The diagnosis is typically based on
physical examination findings , but genetic testing may be utilized to confirm ambiguous cases. Treatment includes surgical debulking of symptomatic tumors, management of seizures and other neurologic complications , and genetic counseling .
Incorrect Answers : B, C , 0. E , and F.
Autosomal dominant disorders with variable penetrance ( Choice B) typically result in less than half of the progeny of an affected parent manifesting the disease , as not all offspring with the mutation will manifest the disease. This patient ' s pedigree instead shows
that slightly more than half of the offspring of affected parents manifest the disease , which is more consistent with complete penetrance.
Autosomal recessive inheritance with either high or low heterozygote frequency (Choices C and D) would necessitate that both parents of the affected offspring either have the disease or are heterozygous carriers . A high heterozygote frequency signifies a low
homozygote frequency (ie , a low frequency of offspring with two mutated alleles) and therefore a low frequency of disease in the offspring . A low heterozygote frequency is conversely associated with a higher frequency of disease in the offspring . In this patient' s
pedigree , the disease : s present in every generation . In autosomal recessive diseases , typically only a single generation is affected , although the risk for disease is increased in consanguineous families.
X - inked dominant or recessive disorders ( Choices E and F ) manifesting in male offspring can only be transmitted maternally. In this patient 's pedigree , the male of generation three receives the mutated allele from his father. In X-linked dominant disorders, both
males and females possessing the mutated allele manifest the disease, while in X - linked recessive disorders , only males with the mutated allele manifest the disease .
Educational Objective : Neurofibromatosis 1 s an autosomal dominant neurocutaneous disorder resulting from an inherited mutation of the NF1 tumor suppressor gene which is transmitted with complete penetrance and variable expressivity. The disorder presents
:
,
with cutaneous neurofibromas ( benign neoplasms derived from neural crest cells), cafe au lait spots , pigmented iris hamartomas (Lisch nodules), optic gliomas, and/or pheochromocytomas.
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8 . One day after being admitted to the hospital for treatment of peritonitis, a 42 -year -old man has progressive shortness of breath and moderate distress . Pulse oximetry on room air shows an oxygen saturation of 53%. Bilateral basilar crackles are heard on
auscultation . Acute lung injury is suspected . The patient is intubated and mechanically ventilated with 90% oxygen at a lung-protective tidal volume of 550 mi_ and respirations of 16/min Positive end- expiratory pressure also should be implemented to prevent
which of the following complications?
A ) Absorption atelectasis
B ) Alveolar overdistention
C ) Oxygen toxicity
D ) Pleural exudate formation
E ) Pulmonary hypertension
F ) Tension pneumothorax
Mechanical ventilation is indicated for respiratory failure . Positive end-expiratory pressure (PEEP) may be utilized to prevent the pressure in the alveoli from dropping to zero or becoming negative during the respiratory cycle . This helps keep alveoli stented open
and able to participate in gas exchange. The patient is suffering acute lung injury and has impaired gas exchange caused by fluid filling the alveoli , resulting in absorption atelectasis . Oxygenation can be improved by implementing positive end-expiratory pressure to
resist alveolar collapse and atelectasis .
Incorrect Answers : B, C, D: 6 and F
Alveolar overdistention ( Choice B) is a potential complication of mechanical ventilation from excessive alveolar pressure . Large tidal volumes and shear stress from alveoli collapsing and opening can resu! t in inflammatory cytokine release and secondary ventilator -
induced lung injury. Lung-proteetiye tidal volume strategies reduce the risk for alveolar overdistension .
Oxygen toxicity ( Choice C) is a potential complication of mechanical ventilation with a high inspired fraction of oxygen . Cell damage occurs secondary to reactive oxygen species: which can worsen lung injury .
Pleural exudate formation (Choice D) is not prevented by positive end -expiratory pressure . Underlying causes for exudative pleural effusion include infection malignancy, and autoimmune disorders.
Pulmonary hypertension ( Choice E ) has numerous potential causes. It may be secondary to conditions such as left heart disease: chronic hypoxemic lung disease , and connective tissue disorders . Positive end- expiratory pressure is not used to prevent pulmonary
hypertension apart from reducing transient hypoxic vasoconstriction.
Tension pneumothorax ( Choice F) is a potential complication of mechanical ventilation , especially with large tidal volumes or high peak pressures that can cause alveolar sac rupture and air communication into the pleura! space. Lung - protective tidal volume
strategies and close monitoring of peak inspiratory pressure reduce the risk for tension pneumothorax formation .
Educational Objective : Oxygenation of mechanically ventilated patients in the setting of acute lung injury is challenging because of reduced lung compliance and absorptive atelectasis from fluid in the alveolar space . Positive end -expiratory pressure can reduce the
amount of alveolar collapse and atelectasis .
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9 . A 4 - year- old boy is brought to the physician by his mother because of a 3-month history of hyperactivity and a decreased attention span . Physical examination shows no abnormalities. Laboratory studies show :
Hemoglobin 10.5 g/dL (N=11—15)
Hematocrit 27% (N= 28%-45%)
Mean corpuscular hemoglobin 24 pg/cell (N= 25.4-34.6)
Mean corpuscular volume 76 gm ^ (N= 77-93)
A photomicrograph of a peripheral blood smear is shown . Which of the fallowing is the most likely underlying cause of these findings ?
A ) Decreased p -globin synthesis

8 } Decreased glucose 6- phosphate dehydrogenase activity
C ) Dietary deficiency of B vitamins
D ) Dietary deficiency of iron
E ) Functional asplenia
F ) Inhibition of ferrochelatase
G) ci -Spectrin mutation
Correct Answer : F.
Although lead is generally no longer used in the manufacture of paint and gasoline , children can continue to be exposed to lead through ingestion of paint chips and dust in older homes or from contaminated drinking water . Lead poisoning is characterized by
basophilic stippling on peripheral blood smear (shown here) and ringed sideroblasts within the bone marrow. Lead poisoning typically affects the central and peripheral nervous systems, the heme synthesis pathway, and gastrointestinal and kidney function. This
patient demonstrates neurobehaviorat symptoms which may be permanent if occurring in youth Children are susceptible to the toxic effects of lead because of an immature central nervous system and lead passage across the blood brain barrier. Acute
encephalopathy, hearing loss and peripheral neuropathy are possible neurologic complications . Clinical manifestations of lead poisoning include renal tubular dysfunction , interstitial nephritis , vomiting , abdominal pain , constipation , and anemia. Lead inhibits the
,
enzymes ferrochelatase and 5- ALA dehydratase, resulting in decreased heme synthesis , increased serum 5- ALA , urinary coproporphyria , and erythrocyte zinc protoporphyrin . The diagnosis is suspected on exposure and symptoms and is confirmed with an
increased serum lead concentration Management of lead poisoning depends on the blood tead concentration and presence of symptoms, and includes chelation with dimercaprol, ethylene diamine tetraacetate , or succimer. Sources of lead should be investigated
and eliminated .
Incorrect Answers : A . 8 . C . D, E and G.
Decreased p -globin synthesis (Choice A) is the cause of p-thalassemia. p-Thalassemia causes microcytic anemia but peripheral blood smear shows microcytosis and target cells with normal iron concentrations . Patients will have an abnormal hemoglobin
,
electrophoresis . It would not explain hyperactivity or decreased attention span.
Decreased glucose 6-phosphate dehydrogenase activity ( Choice B ) is a potential cause of normocytic , hemolytic anemia . Basophilic stippling is not a consistent smear finding , and cells missing sections of their membrane are more commonly seen .
Dietary deficiency of B vitamins (Choice C) including B 6 (pyridoxine ) , B B (folic acid ), and B12 (cobalamin) , are responsible for causing anemia . Pyridoxine causes sideroblastic anemia because of impaired hemoglobin synthesis and excess iron but would not
explain the patient' s hyperactivity or decreased attention span. Folic acid and cobalamin deficiencies , in contrast , cause megaloblastic anemia which would have an increased mean corpuscular volume.
Dietary deficiency of iron (Choice D) is a cause of iron deficiency anemia . This is a microcytic anemia which demonstrates increased total iron binding capacity and decreased ferritin. Fatigue, conjunctival pallor pica , and koilonychia , but not hyperactivity or
decreased attention span, are features of iron deficiency.
Functional asplenia ( Choice E) or hyposplenia leads to retention within red blood cells of basophilic nuclear remnants , or Howell- Jolly bodies. These are typically removed from red blood cells by splemc macrophages. This patient' s peripheral blood smear
demonstrates basophilic stippling not Howell-Jolty bodies . The two can be distinguished by their number, as Howeil -Jolly bodies are usually solitary.
,
a- Spectrin mutation ( Choice G) is a cause of hereditary spherocytosis which causes hemolytic anemia because of the increased osmotic fragility of the atfected red blood ceils . Peripheral blood smear would demonstrate spherocytes rather than basophilic
,
stippling .
Educational Objective: Lead inhibits the enzymes ferrochelatase and 5 - ALA dehydratase , resulting in decreased heme synthesis . Clinical manifestations of lead poisoning include encephalopathy, cognitive dysfunction, peripheral nephropathy, hearing loss , renal
tubular dysfunction, interstitial nephritis, vomiting , abdominal pain, constipation, and anemia .
LL
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10 . A 45 -year- old woman comes to the physician because of a 2 -month history of fatigue, nausea and generalized bone pain. She has had a 2-kg (4.4 -lb) weight loss during this period because of loss of appetite. She has a 4 -month history of renal
,
insufficiency. Her blood pressure is 170/100 mm Hg . Physical examination shows pallor and 2+ pitting edema of the feet . Laboratory studies show anemia . Her serum urea nitrogen concentration is 55 mg/dL and serum creatinine concentration is 4 mg/dL .
Bone x -rays show widened osteoid seams and subperiosteal erosions . Which of the following additional sets of serum findings is most likely in this patient?
1 ,25 -
Calcium Phosphate Parathyroid Hormone
Dihydroxycholecalciferol
A) T
B) 4 T
C) I
D) T I
E) 4
F) 4 4 4
G) 4
Chronic renal disease is a cause of secondary hyperparathyroidism . Secondary hyperparathyroidism typically presents with increased parathyroid hormone (PTH ) : hypoca!cemia: and hyperphosphatemia . It results from chronic renal failure caused by the inability
of the kidney to excrete phosphate , reabsorb calcium , and produce active vitamin D: as the final conversion of 25 -hydroxychalecalci:ferol to active 1 25 -dihydroxycholecalciferol occurs in the kidney via 1-a hydroxylase. Hypocalcemia is exacerbated by the
,
decreased intestinal absorption of calcium in secondary to the deficiency of active vitamin D . Hyperphosphatemia and hypocalcemia result in the upregulation of PTH, which increases bony turnover to raise serum calcium and promotes renal excretion of
phosphate . Unregulated , this process results in renal osteodystrophy, the breakdown of bone caused by excessive PTH stimulus of osteoclasts . This is clinically manifest with widened osteoid seams and subperiosteal erosions , as seen in this patient .
Incorrect Answers : A . EL C, E. F; and G .
While parathyroid hormone and phosphate are ncreased in chronic kidney disease ( Choice A } , calcium and 1. 25 -dihydroxycholecalciferol are decreased , not increased . Active vitamin D is decreased because the kidney parenchyma is the site of its activation and
,
FS lost in chronic disease . Hypocalcemia not hypercalcemia , occurs as a result of the combination of decreased calcium reabsorption , lack of activation of vitamin D , and decreased phosphate excretion.
,
In chronic renal disease , secondary hyperparathyroidism , not hypoparathyroidism (Choices B , C : E , and G) occurs. This is in response to the hypocalcemia that is perpetuated by decreased calcium reabsorption , lack of activation of vitamin D . and decreased
phosphate excretion .
Parathyroid hormone is increased calcium is decreased, and active vitamin D is decreased in chronic renal disease , but phosphate is increased , not decreased ( Choice F ). Patients with kidney failure typically develop an increased serum phosphate because of
,
impaired excretion of phosphate from tubular dysfunction , which does not necessarily relate to increased intraluminal phosphate in the gastrointestinal tract .
Educational Objective: Secondary hyperparathyroidism as a result of chronic kidney disease typically presents with increased PTH , hypocalcemia , and hyperphosphatemia. Serum concentration of 1, 25- dihydroxychalecaldferol is also decreased. Renal
osteodystrophy may ensue .
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11 A 43-year- old man comes to the physician because of a 1 - month history of chronic sinus congestion , occasional bleeding from the nose , and intermittent shortness of breath with exertion. He has had no fever or chilis but has felt very "run down." His
-
temperature is 37.4 ° C (99.3 ° F) , pulse is SB, min . respirations are 16/min, and blood pressure is 160/100 mm Hg . Physical examination shows bilateral maxillary and frontal sinus tenderness to palpation and poor transillumination . Isolated crackles are heard
in the left mid lung. Cardiac examination shows no abnormalities. Laboratory studies show :
Hemoglobin 0.6 g/dL
Hematocrit 2 B%
Serum
Na + 132 rriEq/L
K+ 5 mEq/ L
Cl - 100 mEq/L
HCO 3- 21 mEq/L
Urea nitrogen 48 mg/dL
Creatinine 2.4 mg/dL
Antinuclear antibody negative
Cytoplasmic antineutrophil cytoplasmic antibody ( c- ANCA ) positive
Anti -glomerular basement membrane antibody negative
Urine
pH 6.4
Specific gravity 1.015
Blood 3+
Protein 1+
A chest x - ray shows an infiltrate in the tower segment of the left upper lobe of the lung with normal cardiac silhouette and no significant mediastinal adenopathy. A CT scan of the sinuses shows opacities bilaterally. Which of the following patterns of
inflammatory vascular injury most likely underlies the pathophysiology of this patient ' s disease ?
A ) Eosinophilic vasculitis
6 } Leukocyte clastic vasculitis
C ) Lymphomatoid granulomatosis
D ) Necrotizing granulomatous vasculitis
E ) Temporal arteritis
Granulomatosis with polyangiitis is a systemic necrotizing granulomatous vasculitis that affects small and medium vessels. It is associated with c- ANCA and primarily affects the sinopulmonary tract , kidneys, and skin . Patients typically present with constitutional
symptoms such as fever weight loss and fatigue , with additional symptoms based on speciftc organ involvement . Sinopulmonary manifestations include recurrent sinusitis , otitis media, mastoiditis , nasal ulcerations with epistaxis , hemoptysis , cough , and
,
dyspnea . The kidneys are typically involved , and patients often present with hematuria with an increased risk for developing rapidly progressive glomerulonephritis and renal failure . Skin lesions are common , especially lower extremity purpura .
Incorrect Answers : A . B , C, and E.
Eosinophilic vasculitis ( Choice A) is associated with allergic granulomatous angiitis (Churg -Strauss syndrome) , which is a small vessel vasculitis that may present with asthma, nasal inflammation , and lung , gastrointestinal , cardiac , or kidney involvement .
Pathology shows a granulomatous , necrotizing vasculitis and eosinophilia.
Leukocytoclastic vasculitis ( Choice B ) refers to smal vessel vasculitis that primarily involves the skin . It affects women more than men . and typically presents with a painful , burning rash as well as systemic symptoms of fever weight loss , fatigue , and myalgias .
,
Palpable purpura is commonly noted on physical examination .
Lymphomatoid granulomatosis (Choice C) is a rare iymphoproliterative disorder that most commonly affects the lungs . Patients may also develop a patchy rash and subcutaneous nodules . In this patient , sinopulmonary involvement is more suggestive of
granulomatosis with polyangiitis .
Temporal arteritis ( Choice E) is an autoimmune vasculitis that affects large and medium sized arteries. It is more common in women. Patients classically present with constitutional symptoms jaw claudication and headache . Complications include the permanent
, ,
loss of vision.
Educational Objective : Vasculitis may be categorized by whether sma; medium , or large vessels are affected . Granulomatosis with poliyangiitis is an ANCA -positive necrotizing granulomatous vasculitis of small and medium vessels that is characterized by
sinopulmonary, renal, and skin involvement.
O 0 /=
Exam Section 2: Item 12 o! 50 National Board of Medical Examiners^
12 . A 25 -year- old man is brought to "he emergency department because of a 2 -hour history of nausea vomiting severe abdominal pain and shortness of breath. His respirations are 32 / min . Abdominal examination shows guarding and rigidity. An x-ray of the
, ,
;
chest and upper abdomen with the patient seated upright is shown. Based on these findings , this patient most likefy has which of the following?
A ) Diaphragmatic hernia
B ) Perforated duodenal ulcer
G ) Rectovesical fistula
D ) Tension pneumothorax
E ) Traumatic injury to the liver
Perforation of a duodenal ulcer commonly presents with severe diffuse abdominal pain nausea, vomiting , fever, tachycardia , and septic shock . Bowel contents in the peritoneal space cause rapid infection in the form of peritonitis , marked by abdominal rigidity,
, ,
rebound tenderness , and guarding . An upright chest x -ray may show air under the diaphragm (pneumoperitoneum) caused by leakage of bowel contents into the peritoneal cavity , as in this patient . Perforated viscus (and resultant peritonitis ) constitutes a surgicai
emergency requiring exploratory laparotomy to identify and repair any perforation, lavage the peritoneum and prevent or control sepsis , manage exsanguination if vessels are involved, and resect any necrotic bowel . Broad spectrum antibiotics are also indicated .
Incorrect Answers : A , C , D, and E.
Diaphragmatic hernia ( Choice A) describes the presence of abdominal contents within the thorax , and can present with chest pain , shortness of breath , and bowef sounds within the lung fields. It most commonly occurs in the left hemithorax and may be visualized
as intestinal loops on radiographs.
Rectovesical fstula ( Choice C ) is a condition in which there is an abnormal connection between the rectum and the urinary bladder. This can lead to complications of urine leakage through the rectum and urinary tract infections plus pneumaturia . It would not
cause pneumoperitoneum .
Tension pneumothorax ( Choice D) occurs when air accumulates within the pleura] cavity to an extent that results in compression and shifting of the mediastinal structures . Such structure compromise results in impaired venous return leading to diminished cardiac
,
output it typically presents as severe respiratory distress jugular venous distention tracheal deviation diminished breath sounds , hyperresonance to percussion and hemithorax hyperinflation. Vital signs disclose tachypnea , tachycardia , and hypotension.
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Traumatic injury to the liver ( Choice E ) , such as a liver aceration , could present with abdominal pain and peritonitis as a result of blood causing irritation and inflammation the peritoneum . However , it would not cause pneumoperitoneum.
Educational Objective: Perforation of a duodenal ulcer commonly presents with severe , diffuse abdominal pain nausea , vomiting fever, tachycardia , and septic shock . An upright chest x-ray may show air under the diaphragm (pneumoperitoneum) caused by
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leakage of bowel contents into the peritoneal cavity.
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13. A 32 -year- old man begins to laugh while eating dinner with his friends. A small particle of food irritates his larynx and provokes him to cough. Which of the following best describes the position of his vocal cords throughout this sequence?
Immediately After
While Swallowing Laryngeal Irritation While Coughing
A) Closed closed open
B) Closed open closed
C) Closed open open
D) Open closed closed
E) Open closed open
F) Open open closed
Coughing can be a voluntary or reflexive action that protects the airway from aspiration , foreign bodies and environmental irritants : and clears bronchial secretions and debris . The forceful expulsion of air requires coordinated mechanics between the respiratory
,
muscles and laryngeal structures . While swallowing: the vocal cords are dosed to prevent inadvertent introduction of food into the airway and lungs . Immediately after laryngeal irritation the vocal cords and epiglottis remain ciosed while the respiratory muscles
:
contract to generate increased pressure in the airways . While coughing : the vocal cords open to allow forceful exhalation of air to remove the irritant . Respiratory muscle weakness and neuromuscular disorders that interfere with the coordinated mechanics of
cough are risk factors for aspiration and associated pneumonia .
Incorrect Answers : 8, C D: E and F.

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Choices D, E and F are incorrect as the epiglottis is inverted and the vocal cords are closed during swallowing to protect the airway and fungs .
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Choices B C and F are incorrect as the vocal cords remain closed as the cough reflex arc is initiated by Earyngea ! irritation in order to generate pressure with the trapped air in the lungs.
; ;
Choices B . D . and F are incorrect as the vocal cords must open during the cough to allow air to escape the Eungs and remove the offending irritant .
Educational Objective: Coughing is a protective mechanism for clearing material from the airways. To generate high positive pressure for expefling air from the lungs the vocal cords close as the respiratory muscles contract , trapping air in the lungs. Opening of
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the vocal cords then allows a forceful expulsion of air to occur.
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14 . A 25 -year- old man comes to the physician because of abdominal pain and vomiting for 1 day. He has had greasy yellow plaques on his skin and recurrent abdominal pain following ingestion of fatty meals since infancy. Physical examination shows
xanthomas over the trunk and lipemia retinalis . There is tenderness over the epigastrium. and bowel sounds are decreased . Laboratory studies show leukocytosis and an increased serum amylase activity. The plasma appears milky. Which of the following
,
is most likely increased in this patient' s serum?
A ) ApoAll
B ) Chylomicrons
C ) Free cholesterol
D ) HDL -cholesterol
E ) LDL- cholestero !
The patient is presenting with characteristic features of familial hyperchylomicronemia. a genetic lipid disorder caused by lipoprotein lipase deficiency. Lipoprotein lipase catalyzes the conversion of triglycerides carried by circulating chylomicrons into fatty acids in
extrahepatic tissue . The fatty acids can then be absorbed by cells for use in metabolism. Lipoprotein fipase deficiency is marked by increased serum concentrations of chylomicrons and triglycerides . Patients typically present with abdominal pain fallowing ingestion
of fatty meals and steatosis . Physical examination may disclose eruptive xanthomas and lipemia retinalis ( cream -colored discoloration of the retina ] vessels associated with hyperchylomicronemia ) . Build-up of chylomicrons and triglycerides in the serum results in a
milky appearance and increased amylase activity.
incorrect Answers : A . C D , and E.

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Apo A ll ( Choice A ) is a protein that is found in HDL -choEesterol and is not involved in chylomicron transport and processing . Apo C -il is a component of VLDL- cholesterol and chylomicrons , and it activates lipoprotein lipase. Deficiency of Apo C- l can also result in
familial hyperchylomicronemia.
Free cholesterol ( Choice C) concentrations are not typically increased in hyperchylomicronemia , and the condition is not associated with an increased risk for atherosclerosis , as with other lipid disorders.
HDL-cholesterol ( Choice D ) is composed of the apolipoproteins ApoA -1, ApoC-IL and ApcE HDL concentrations are not increased in hyperchylomicronemia .
LDL- cholestero I ( Choice E) is primarily composed of the apoiipoprotein ApoB - 1D 0: which mediates binding to the LDL- receptor on hepatocytes . LDL concentrations are increased in familial hypercholesterolemia and combined hyperlipidemia
Educational Objective : A deficiency in lipoprotein lipase results in familial hyperchylomicronemia caused by the inability of endothelial cells to catalyze the breakdown of triglycerides from circulating chylomicrons . Patients present with abdominal pain following
ingestion of fatty meals.
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15. A 48 -year- old man comes to the physician because he is concerned about a pigmented lesion that has enlarged and changed color during the past 3 months. Physical examination shows a 2 -cm oval! lesion. Histologic examination of an excisional biopsy
specimen shows melanoma. If a biopsy of the lesion had been done prior to the malignant transformation which of the following would have been the most likely diagnosis ?
,
A ) Acanthosis nigricans
B ) Actinic keratosis
C ) Freckle
D ) Nevocelfular nevus
E ) Seborrheic keratosis
Malignant melanoma is likely to be present when a lesion demonstrates asymmetry, irregular -appearing borders , variable coloration , a diameter greater than 6 mm . and rapid evolution in characteristics . It is a neoplastic proliferation of melanocytes and can develop
within a giant congenital nevus (nevocellular nevus ). Compared to acquired nevi, congenital nevi tend to be larger, darker in color , thicker, and more likely to contain hair. These nevi should be monitored by the patient for development of any features concerning for
malignant degeneration . Malignant melanoma has the ability to rapidly invade and metastasize, which carries a poor prognosis when diagnosed late . Subtypes include superficial spreading , nodular lentigo maligna, and acral lentiginous. Any lesion with features
suggestive of malignant melanoma should be surgically excised with negative margins and pathologically examined for the depth of dermal invasion .

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Acanthosis nigricans { Choice A ) is characterized by hyperpigmented , velvety patches seen or the neck upper back , breasts , and axillae which is a marker of metabolic syndrome and diabetes mellitus. It is neither premalignant nor malignant and there are no
,
atypical cells on histopathologic examination .
Actinic keratosis ( Choice B ) is a premalignant lesion that may progress to squamous cell carcinoma . They present as chronic rough , scaly patches of skin in areas of prolonged sun exposure ( eg . face, ears hands) .
Freckle ( Choice C ) , or ephelis , is a benign , light tan macule which darkens with sun exposure . It is caused by an increase in melanin production and is neither premalignant nor malignant .
Seborrheic keratosis ( Choice E) is a benign proliferation of the epidermis ; lesions exhibit a greasy, adherent appearance. While seborrheic keratoses are often brown, this is because of the keratin produced by the epidermis rather than melanin.
Educational Objective: Melanoma should be suspected when lesions demonstrate asymmetry, border irregularity, multiple colors diameter greater than S mm , or changing features it may arise from a preexisting congenital nevus (nevocellular nevus).
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16 . The high therapeutic index displayed by acyclovir and its derivatives in treating herpesvirus infections is due to the fact that the drug must be activated by a viral enzyme . Which of the following enzymes is most likely being described ?
A ) DNA ligase
B ) Guanylyltransferase
C ) Thymidine kinase
D ) Uracil DNA glycosyEase
E ) Viral protease
Herpetic infections are treated with drugs that inhibit viral DNA polymerase: classically by guanosine analogs such as acyclovir valacyclovir, and famciclovir . Prior to exerting their antiviral effects , guanosine analogs must be phosphorylated by the viral enzyme
thymidine kinase . Phosphorylation is the process by which a phosphate group is added to the molecule. These molecules are then able to inhibit the viral DMA polymerase by terminating the nascent DNA chain during replication. These drugs are effective against
herpes simplex virus and varicella zoster virus , weakly effective against Epstein-Barr virus and not effective against cytomegalovirus . Development of a mutation in the viral thymidine kinase enzyme would prevent drug phosphorylation and confer resistance to
,
guanosine analog medications .
Incorrect Answers : A . El . D, and E.
DNA ligase ( Choice A) is an enzyme related to DNA replication and modification . It joins Okazaki fragments together by catalyzing the synthesis of the phosphodiester bond within double -stranded DNA . It does not interact with guanosine analogs .
Guanylyltransferase (Choice B) is an enzyme which transfers a guanosine monophosphate group to another molecule , usually pyrophosphate , in the process of mRNA formation. While the class of medications used to treat herpetic infections are guanosine
analogs , they are activated by phosphorylation, not via transfer of or to a larger group.
Uracil DNA glycosylase ( Choice D) is a component of the base excision repair pathway and removes uracil groups from DNA which form from deamination of cytosine residues . It is not involved in the activation of guanosine analogs .
;
Viral proteases ( Choice E ) cleave the initial polypeptides produced by the translation of viral RNA into smaller, functional parts . Protease inhibitors are used in the treatment of hiV and include darunavir, indinavir ritonavir and saquinavir .
, ,
Educationa - Objective: Acyclovir, famciclovir, and valacyclovir are guanosine analogs that inhibit viral DNA polymerase and are used to treat herpes simplex virus infections. Guanosine analogs require phosphorylation by thymidine kinase to be activated .
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17. A 54-year- oid man comes to the physician because of a 2 -week history of burning epigastric pain. He is recently divorced. His diet mainly consists of fast food . He smokes cigars and drinks one to two 12 -ounce cans of beer on the weekends . He was
treated for Helicobacter pylori infection 1 year ago. He uses high doses (600 mg daily) of over-the-counter ibuprofen for chronic joint pain. Abdominal examination shows tenderness to deep palpation of the epigastric area. A peptic ulcer is suspected . Which
of the following is the strongest predisposing risk factor for this patient' s condition?
A ) High-fat diet
B ) Ibuprofen use
C ) ingestion of alcohol
D ) Recent psychosocial stressor
E ) Smoking cigars
Peptic ulcer disease describes the presence of ulcers in the stomach or duodenum , which classically present with worsening abdominal pain related to consumption (gastric ) or lack of consumption (duodenal) of food . The most common cause of peptic ulcer
disease is infection with the bacterium Helicobacter pylori ., which accounts for nearly all duodenal ulcers Gastric ulcers can be caused by prolonged or excess usage of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen , which inhibit cyclooxygenase
in the gastrointestinal tract , leading to a reduction of prostaglandin secretion and decreased protection of the gastric mucosa . Persistent inflammation related to a peptic utcer can result in complications including fibrosis , stricture hemorrhage , and perforation .
,
Proton pump inhibitor therapy is first line in the management of gastroesophageal reflux and peptic ulcer disease along with eradication of H. pylori and cessation of inciting factors (eg , smoking alcohol, NSAIDs) .
,
incorrect Answers : A . C , D , and E.
High-fat diet (Choice A) can be related to biliary colic or hepatobiliary pathology. Biliary co ic is characterized by epigastric or right upper quadrant pain after ingestion of a fatty meai promoting gallbladder contraction .
Ingestion of alcohol ( Choice C ) in excessive amounts can cause damage to the gastric mucosal barrier. This patient drinks a moderate amount of alcohol occasionally making it unlikely to be the strongest cause of his peptic utcer disease .
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Recent psychosocial stressor ( Choice D) has been associated to a limited extent with increased risk for peptic ulcer disease . However, NSAID use has a stronger association with the development of peptic ulcer disease .
Smoking cigars ( Choice E) has been associated with peptic utcer disease. Risk for peptic ulcer disease increases accordingly with increasing pack-years of smoking . This patient smokes cigars intermittently ; it is not the strongest predisposing risk factor.
Educational Objective : Peptic ulcer disease presents with epigastric or left upper quadrant abdominal pain in association with meals . It is caused by infection from H. pylori , or from inciting factors that compromise the gastric mucosal barrier such as NSAIDs
smoking, and alcohol use .
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18. A 27 -year- old woman delivers monozygotic twins at 34 weeks ' gestation . The larger twin has a hematocrit of 6 S%; the smal - er twin is pa :e and has a hematocrit of 25%. Which of the following is the most likely explanation for these findings ?
A ) Amniotic fluid leak across intervening membranes

B ) Artery -to- artery chorionic surface anastomoses
C ) Chronic abruptio placentae
D ) Funisitis
E ) Knotting of the umbilical cords
F ) Oligohydramnios
Twin-twin transfusion syndrome (TITS) and twin anemia polycythemia sequence (TAPS ) are complications of monochorionic twin gestation , S occurs because of the formation of arteriovenous anastomoses in the chorion of the placenta that allow blood to pass
from one fetus to the other Less commonly it can also involve the formation of artery -to- artery chorionic surface anastomoses . It typically presents on prenatal ultrasound with unequal amniotic fluid indices between the two amniotic sacs it can also present with
, ,
anemia of one fetus and polycythemia of the other fetus when chronic , which is referred to as TAPS . Monochorionic twin gestations are typically monitored with serial ultrasounds to watch for the development of these conditicns: as they have a high morbidity and
mortality. Ultrasound findings also include discrepancies in nuchal transtucency and crown - rump length , and abnormal ductus venosus flow. Inequalities in amniotic fluid distribution are caused by relative hypovolemia of one fetus , with resultant activation of the
renin- angiotensin-aldosterone system and consequent oliguria . In contrast the hypervolemia of the other twin causes release of atrial natriuretic peptide which results in diuresis and relative increases in the amniotic fluid index . Complications of this syndrome also
, ,
include congenital anatomic abnormalities , hydrops fetalis , heart failure and growth restriction . Options for management include laser ablation of the anastomotic vessels , amnioreduction, and/or selective fetal reduction .
,
Incorrect Answers : A . C , D . E , and F.
Amniotic fluid leak across intervening membranes ( Choice A) could lead to oligohydramnios in one fetus and polyhydramnios in the other fetus if the movement of fluid was unidirectional. However movement of amniotic fluid from one fetus to another would not
,
cause discordant hematocrit values in the newborns.
Chronic abruptio placentae (Choice C) presents with intermittent vaginal bleeding, oligohydramnios caused by placental insufficiency, and fetal growth restriction. As monozygotic twins share a placenta , chronic abruptio placentae would be expected to affect both
fetuses similarly.
Funisitis ( Choice D ) is an infection of the umbilical cord that occurs in the setting of chorioamnionitis. Chorioamnionitis is a bacterial infection of the fetal membranes that most commonly occurs with premature or prolonged rupture of membranes. Funisitis would not
cause an alteration in hematocrit concentrations in the newborns .
Knotting of the umbilical cord ( Choice E ) can lead to fetal hypoxemia caused by cord compression during fetal descent through the vaginal canal . However knotting of the umbilical cords is relatively rare and would likely only occur in monochorionic monoamniotic
twins . It would not affect hematocrit concentrations in either fetus.
Oligohydramnios ( Choice F) presents with a low amniotic fluid index and can result from premature rupture of membranes , postdate pregnancies, or abnormalities of the fetal genitourinary tract , as well as LS. Complications include intrauterine growth restriction
but do not include anemia or polycythemia .
Educational Objective : Twin-twin transfusion syndrome is caused by arteriovenous anastomoses in the chorion of monochorionic twins with resultant movement of red blood cells and plasma from one fetus to the other. Complications include twin anemia
polycythemia sequence, discordant amniotic fluid indices , congenital anatomic abnormalities , hydrops fetalis heart failure , and intrauterine growth restriction.
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19. A 55 -year- old homeless man comes to the emergency department because of a 2 -month history of intermittent fever cough productive of blood -tinged sputum , night sweats and fatigue: he has had a 3.2 -kg ( 7-lb ) weight loss due to decreased appetite
,
during this period On arrival he is cachectic and has a chronic cough. His temperature is 38DC (1G 0.4T ). Rhonchi are heard over the right upper lobe . A chest x-ray shows areas of cavitation in the right upper lobe . Which of the following is the most likely
cause of tissue injury in this patient' s condition?
A ) Antigen-antibody complex deposition

B ) Arthus reaction
C ) Delayed-type hypersensitivity
D ) Pseudomembrane formation
E ) Wheal and flare reaction
Delayed-type hypersensitivity reaction , also known as a type IV hypersensitivity reaction, most likely accounts for this patient ' s lung injury in the setting of pulmonary tuberculosis . Type IV hypersensitivity is characterized by a cell-mediated response which involves
maturation of antigen specific CD4+ or CD3+- T lymphocytes which in this case, are antigens specific to Mycobacterium tuberculosis (MTB), When the antigen is encountered. CD4+ T lymphocytes release cytokines leading to inflammation and macrophage
,
activation, while CD3+ T lymphocytes directly kill cells expressing the antigen . Activated macrophages become histiocytes and form granulomas , which in the case of MTB . may be caseating granulomas. Local inflammation at the site of MTB infection is an attempt
to encapsulate and /or destroy MTB , but the local immune response results in substantial damage to the surrounding lung parenchyma .
incorrect Answers : A . B , D , and E.
Antigen-antibody complex deposition ( Choice A ), also called a Type 111 hypersensitivity reaction, : s a result of immune complex (antigen-antibody) deposition in tissues resulting in a local inflammatory response and complement fixation with subsequent damage to
tissues. Common diseases in which this plays a role include polyarteritis nodosa, systemic lupus erythematosus , and serum sickness.
Arthus reaction ( Choice B ) is a localized type li ( antigen- antibody complex ) hypersensitivity reaction whereby complexes that fix complement deposit in blood vessels and cause local necrosis. It occasionally occurs with hepatitis B or tetanus vaccines although this
,
is uncommon .
Pseudomembrane formation ( Choice D ) occurs in infection with Clostridium difficile , a bacterium that causes colitis in patients with recent exposure to antibiotics . Colonoscopy classically shows pseudomembranes on the surface of cotonic mucosa.
Pseudomembrane formation is not a characteristic of MTB infection .
Wheal and flare reaction ( Choice E ) indicates the presence of mast celt degradation and typically manifests as hives. The cause may be related to medication effects , heat or cold exposure , allergies , or may be idiopathic .
Educational Objective: MTB infection induces a type IV (delayed-type) hypersensitivity reaction in which MTB antigens induce maturation of CD 4 + and CD8 + T lymphocytes specific to that antigen . It results in a local inflammatory response , with direct cytotoxic
killing of infected cells by CD8+ T lymphocytes and stimulation of macrophage activation with subsequent granuloma formation.
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20 . A 45 -year- old man who is a firefighter comes to the physician because of a 3-month history of persistent cough and repeated fung infections. He has smoked 2 packs of cigarettes daily for 30 years. His respirations are f 6/min . Physical examination shows
dry cough and decreased lung sounds. A chest x-ray shows no abnormalities . Histologic examination of this patient' s respiratory epithelium is mostlikeiy to show which of the following types of metaplasia ?
A ) Columnar
B ) Connective tissue
C ) Neuroendocrine
D ) Squamous
E ) Transitional
Chronic tobacco use is associated with numerous detrimental changes to the respiratory system . Tobacco smoke directly disrupts the ability of the airway to clear foreign material by resulting in increased mucus production and secretion by the respiratory
epithelium , decreased activity of airway cilia and inhibition of alveolar macrophage function. Chronic irritation from tobacco exposure also results in squamous metaplasia of the respiratory epithelium, which is normally primarily composed of pseudostratified
;
columnar cells in the trachea and bronchi and cuboidal cetls in the bronchioles. Squamous metaplasia is a preneoplastic lesion that has the potential to transform into squamous ceil carcinoma, which is the second most common type of primary lung cancer
following adenocarcinoma . Features associated with squamous cell carcinoma of the lung include pulmonary cavitations , central location and hypercalcemia caused by paraneoplastic parathyroid hormone - related peptide (PTHrP ) production.
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Columnar ( Choice A ) metaplasia occurs with Barrett esophagus because of chronic chemical irritation from gastric contents . The normal squamous epithelium of the esophagus transforms into columnar epithelium and is associated with an increased risk for
esophageal adenocarcinoma.
Connective tissue (Choice B) metaplasia refers to abnormal formation of mesenchymal cells ( bone , cartilage , adipose ) in tissue. An example is myositis ossificans , the formation of bone in muscle tissue that may occur following trauma .
Neuroendocrine ( Choice C) tumors of the lung , such as small cel lung cancer, result from hyperplasia and malignant transformation of normal neuroendocrine cells residing in the lung , rather than metaplasia in response to an irritant .
Transitional ( Choice E } epithelium is located in the genitourinary tract and undergoes metaplasia to squamous epithelium in response to injury, which may be a precursor to bladder cancer
Educational Objective: Metaplasia is the replacement of one differentiated cell type by another in response to normal maturation signals or abnormal irritants . The presence of metaplasia can be a risk factor for developing tissue -specific neopiasms Metaplasia of
squamous cells in the respiratory epithelium is a risk factor for squamous cell carcinoma of the lung .
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21. In an animal model of ischemic myocardial injury, a branch of the coronary artery is clamped. Which of the following morphologic changes is most likely to occur first?
A ) Defects in the plasma membrane

B ) Myelin figures
G ) Nuclear pyknosis
D ) Rupture of lysosomes
E ) Swelfing of the endoplasmic reticulum
Correct Answer : E
Swelling of the endoplasmic reticulum ( ER ) is most likely to be the first morphologic change that will occur after clamping a branch of the coronary artery. Myocardial cells have a high metabolic demand , and complete cessation of blood flow to the myocardium leads
to myocardial ischemia . If blood flow is not restored , myocardial ischemia progresses to myocardia infarction , at which point cardiomyocyte apoptosis occurs . One of the first cellular changes that occurs after cessation of blood flow is swelling of the cel! and its
organelles, including the ER . Decreased oxygen impairs the ability of the cell to generate ATP, which is used to pump sodium out of the cell and potassium into the cell via the action of the NaT-K +-ATPase in the plasma membrane . Cessation of this pump results in
intracellular accumulation of sodium , thereby shifting the osmotic gradient and leading to cellular swelfing . As protein synthesis is an energy intensive process , ischemia can also alter the folding of cellular proteins These proteins accumulate in the ER . This process
triggers the unfolded protein response which seeks to restore normal function by degrading unfolded or misfolded proteins and by downregulating protein synthesis. If unsuccessful , the unfolded protein response induces apoptosis . If blood flow is restored , these
,
changes can be reversed and cardiomyocyte apoptosis is avoided .

,
Incorrect Answers : A . B , C and D.

;
Defects in the plasma membrane { Choice A) leading to increased plasma membrane permeability is a feature of early coagulative necrosis and indicates irreversible cellular damage that is the hallmark of myocardial infarction. Similarly, nuclear pyknosis ( Choice C )
describes the condensation of nuclear chromatin that occurs as the celi is undergoing apoptosis, while the rupture of lysosomes ( Choice D ) is also a feature of irreversible cell injury.
Myelin figures ( Choice B) describe cytoplasmic structures that resemble in appearance the myelin fibers associated with neurons , although they are unrelated. Myelin figures are aggregates of phospholipids from damaged mitochondria and ER . They can be seen in
both reversible and irreversible cellular injury and are a later finding than swelling of the ER .
Educational Objective: Myocardia! ischemia from cessation of coronary blood flow describes a stepwise process of cellular : injury. One of the first manifestations of cardiomyocyte injury is swelling of the cell and its organelles , which occurs as the intracellular
accumulation of sodium leads to an alteration in the osmotic gradient . Ef blood flow is not restored, apoptosis eventually occurs .
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22 . An investigator is conducting a study of the effect of salt intake on renal function. The diet of an experimental animal is modified to contain only 25% of normal salt content. Which of the following is most likely to be increased in this experimental animal?
A ) Epithelial sodium channel transcription

B ) Extracellular fluid
C ) Plasma atrial natriuretic peptide concentration
D } Serum potassium concentration
E ) Urine pH
The nephron is characterized by an apical epithelial membrane that faces the tubular lumen and a basal layer that faces the interstitium . This epithelial membrane , whether in the convoluted tubules loops, or collecting duct is the site of reabsorption of solute or
,
water into the blood . The collecting duct is the terminal segment of the nephron and reabsorbs sodium and water wliiie secreting potassium and protons: primarily through epithelial sodium channels and aquaporins. It is the site of action of aldosterone . Increased
dietary salt intake suppresses aldosterone , while decreased dietary salt intake increases aldosterone activity. Aldosterone increases epithelial sodium channel transcription and activity, resulting in increased sodium reabsorption .
Incorrect Answers : B, C, D and E.

;
Increased dietary sodium can lead to fluid accumulation in extracellular tissue . Decreased dietary saltwoufd be unlikely to increase extracellular fluid ( Choice B ) .
Plasma atrial natriuretic peptide ( ANP ) concentration ( Choice C) would likely be decreased with low salt intake . AMP is a hormone secreted by atrial cardiac myocytes in response to increased hydrostatic pressure . It results in diuresis , natriuresis . and decreased
blood pressure .. Decreased dietary salt intake generally decreases systolic blood pressure in hypertensive individuals , whereas increased dietary salt intake would be more likely to increase blood pressure and therefore plasma ANP concentration .
Decreased dietary salt would increase aldosterone activity, which increases epithelial sodium channel activity and apical potassium secretion , leading to decreased , not increased , serum potassium concentration ( Choice D).
Aldosterone causes increased H+ -ATPase activity, resulting in H * secretion into the urine This would decrease , not increase , urine pH ( Choice E ).
Educational Objective: Increased dietary salt intake suppresses aldosterone , while decreased dietary salt intake increases aldosterone activity. Aldosterone increases epithelial sodium channel transcription and activity, resulting in increased sodium reabsorption .
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23 . A 5 G -year- old woman comes to the physician because of cough productive of blood-tinged sputum for 8 days. She also has had fatigue loss of appetite and an unintentional 6.8-kg (15- lb ) weight loss during the past 2 months. She has a 5 -year history of
^ examination shows dullness to percussion over the right lower lung lobe . A chest x- ray shows a mass in the right
chronic cough and shortness of breath that she had attributed to smoking 2 packs of cigarettes daily for 42 years . She appears ill. Physical
:
upper lung lobe . The gross and microscopic appearances of a lung from a patient with a similar condition are shown. Which of the following is the most likely type of neoplasm in this patient?
A ) Adenocarcinoma
B ) Giant cell carcinoma
C ) Large cell undifferentiated carcinoma
D ) Small cell carcinoma
E ) Squamous cell carcinoma
Correct Answer : E
Squamous cell carcinoma of the lung which typically presents as a central ' esion . is the second most common type of primary lung cancer following adenocarcinoma, which more often presents as a peripheral lesion . Risk factors for all major types of lung cancer
;
include tobacco use: secondhand smoke asbestos and radon exposure , and a family history of lung cancer Features associated with squamous cell carcinoma of the lung include pulmonary cavitations , central location , and hypercalcemia caused by
; ,
paraneoplastic parathyroid hormone -related peptide (PTHrP) production. Histologic characteristics include polygonal ceils with intercellular bridges , eosinophilic cytoplasm , keratin pearls ( as seen in the photomicrograph) , and extensive necrosis . Lung cancer, in
general , typically presents with cough , unintentional weight loss, hemoptysis , chest pain dyspnea , and hoarseness ; occasionally, wheezing , focal rhonchi , or hypertrophic osteoarthropathy may be noted on examination . Obstruction of the airways can lead to
,
recurrent postobstructive pneumonia . Diagnosis is made by chest imaging and examination of a biopsy specimen. Prognosis is a function of the cancer type along with grading and staging of the disease. If is often detected once metastatic , at which point the
prognosis is poor.
Incorrect Answers : A . B , C , and D.
Adenocarcinoma ( Choice A) of the lung is the most common overall primary tung cancer and the most common among nonsmokers . It typically presents as a chronic consolidation in the periphery of the lung rather than centrally. A glandular pattern is classically
seen on histology with mucin-positive staining .
Giant cell carcinoma ( Choice B) is a rare carcinoma of the lung that contains pleomorphic giant , multinucteated cells on histology ft most commonly involves the upper lobes and the lung periphery.
,
Large cell undifferentiated carcinoma ( Choice C ) is a neoplasm of epithelial ce is that lacks glandular, squamous , or neuroendocrine characteristics on histology. It most often presents as a peripheral lesion.
Sma I celt carcinoma ( Choice D ) is also centrally located and associated with tobacco use. It is a neoplasm of neuroendocrine cells and is associated with numerous paraneoplastic syndromes including Cushing syndrome , syndrome of inappropriate antidiuretic
,
hormone , Lambert-Eaton myasthenic syndrome caused by presynaptic calcium channel antibody production, paraneoplastic limbic encephalitis , and subacute cerebellar degeneration. Histologic features include small , dark bue tumor cells lacking nucleoli with a
high nuclear to cytoplasm ratio .
Educational Objective: Centrally located primary lung cancers include squamous cell carcinoma of the lung and small cell carcinoma of the lung . Squamous celi carcinoma is the more common subtype and is associated with polygonal cells with intercellular
bridges and keratin pearls on histology.
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X 24 . Two days after admission to the hospital because of a sickle cell disease crisis a 24 -year- old man suddenly develops blood in his urine and flank pain . Laboratory studies at the time of admission showed that his hematocrit was decreased to 11 % from his
:
normal baseline of 25 % . Urinalysis shows gross talood rare WBCs: and no W6C casts . Which of the following is the most likely cause of the hematuria in this patient?
;
A ) Glomerulonephritis
B ) Nephrolithiasis
C ) Prostatitis
D ) Renal papillary necrosis
E ) Transitional cell carcinoma
Renal papillary necrosis (RPN) occurs following Ischemic , inflammatory, infectious , or toxin-mediated damage to the renal papilla and describes the sloughing and loss of the papillae including substructures such as the distal collecting tubule. RPN can be triggered
by infections ( egr acute pyelonephritis) , diabetes mellitus . sickle cell disease , or nonsteroidal anti-inflammatory medications (NSAIDs ) . In sickle cell disease renal papillary necrosis is common and occurs secondary to renal medullary ischemia and infarction. It
,
typically presents with hematuria and acute flank pain . It can also be complicated by urinary tract obstruction and/or infection secondary to necrotic tissue sloughing into the renal collecting system and ureters . It characteristically presents with gross hematuria and
proteinuria on urinalysis .

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Glomerulonephritis (Choice A) refers to a variety of glomerular diseases , including nephritic and nephrotic syndromes . Nephritic syndromes typically present with acute renal failure with associated hematuria , red blood cell urine casts , and hypertension . Nephrotic
syndrome typically presents with excessive proteinuria ( greater than 3g per day ) hyperlipidemia , hypoalbuminemiar and edema. It would not typically cause ureteral obstruction .
Nephrolithiasis ( Choice B) typically presents with unilateral flank pain that is colicky and sometimes radiates to the groin with associated hematuria . In a patient with sickle ceil crisis , renal papillary necrosis is a more likely cause of flank pain and hematuria.
Prostatitis (Choice C ) can present with dysuria , frequency, and urinary urgency similar to a urinary tract infection . On examination , a tender boggy, enlarged prostate can be palpated and treatment is with antibiotics. Urinalysis would show WBCs and would be
,
unlikely to indicate hematuria.
Transitional cel! carcinoma ( Choice E) is the most common tumor of the urinary tract system and typically presents with painless gross hematuria . It is associated with smoking , aniline dyes, and cyclophosphamide .
Educational Objective : Renal papillary necrosis (RPN) occurs following Ischemic , inflammatory, infectious , or toxin-mediated damage to the renal papilla and describes the sloughing and loss of the papillae including substructures such as the distal collecting tubule .
RPN can be triggered by infections (egr acute pyelonephritis), diabetes mellitus , sickle cell disease , or NSAIDs . It typically presents with gross hematuria and proteinuria on urinalysis.
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25. A 20-year- old woman comes to the office because of a 1-month history of a mass in her neck . She has a 16 - year history of cerebellar ataxia and progressive scleral telangiectatic lesions. Her brother has a simi ar condition. Physical examination shows a
large: firm; nonmoveable lymph node palpable in the left anterior side of the neck. A biopsy specimen of the node shows evidence of Hodgkin lymphoma . Which of the following genetic mechanisms is the most likely cause of this patient' s lymphoma ?
A ) Activation of a tumor suppressor gene

B ) Deletion of the 6 CL gene
C ) DNA repair defect
D } Initiation of somatic hypermutation
This patient with ataxia telangiectasia possesses a genetic mutation of the ATM gene leading to a DMA repair defect The ATM gene product delays the progression of cells with DNA damage through the cell cycle , which allows the cell to repair the DNA . When the
ATM gene product is defective , somatic mutations accumulate , leading to the dysfunction of diverse proteins and an increased risk for malignancy. Patients present with cerebellar atrophy and progressive ataxia , telangiectatic lesions of the eyes and exposed areas
of the skin , and other movement abnormalities such as dystonia, abnormal eye movements (eg, saccades) and decreased immunoglobulin concentrations (IgA , lgG: and IgE). Conditions associated with ataxia telangiectasia include pulmonary disease (eg ,
;
bronchiectasis from recurrent sinopulmonary infections) and hematologic malignancies such as Hodgkin lymphoma . Ataxia telangiectasia demonstrates an autosomal recessive inheritance pattern. Management requires the surveillance and treatment of disease
complications .
Incorrect Answers : A, B . and D .
Activation of a tumor suppressor gene ( Choice A ) such as P53 would arrest the cell cycle . Activating tumor suppressor genes would decrease cellular proliferation and would not result in malignancy.
Deletion of the BCL gene (Choice B) may result in hematologic deficiencies such as anemia . The BCL gene is an oncogene that normally inhibits apoptosis and may promote malignancy (eg follicular lymphoma ) when activated .
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Initiation of somatic hypermutation ( Choice D ) occurs during normal immunoglobulin class switching . Somatic hypermutatian is not directly associated with malignancy.
Educational Objective : Ataxia telangiectasia is an autosomal recessive disorder resulting from a DMA repair defect. Consequently, somatic mutations accumulate leading to protein dysfunction and an increased susceptibility to hematologic malignancy such as
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Hodgkin lymphoma . Patients typically present with progressive ataxia , telangiectasias ., abnormal eye movements , and decreased immunoglobulin concentrations ( leading to recurrent sinopulmonary infections ) .
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26. A 45 -year- old woman comes to the physician because of a 3 -week history of pain over her ateral left hip that is most severe when she awakens in the morning . She is unable to sleep on her eft side due to the pain. Range of motion of the left hip is full with
no pain on internal or external rotation. There is tenderness to palpation over the lateral hip. Sensation is intact . Inflammation of which of the following structures is the most likely cause of this patient' s symptoms ?
A ) Hip joint
B ) Inguinal ligament
C ) Lateral femoral cutaneous nerve
D ) Sacroiliac joint
E ) Trochanteric bursa
Correct Answer : E
Bursae are thin : sac-like, fluid-filled structures that reduce friction and permit motion between layers of connective tissue. Bursae are frequently implicated in pathology and are often associated with pain and swelling,; such as the subacromial bursa which can ,
cause pain in the shoulder the trochanteric bursa : which can cause pain over the lateral aspect of the hip (in this case) , and the olecranon bursa , which can cause pain and swelling posterior to the elbow. When inflamed or injured, fluid can collect inside the
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potential space of the bursa causing swelling, which can be appreciated on examination as a fluctuant , tender , circumscribed mass . Trochanteric bursitis presents with pain to palpation over the affected bursa and swelling and erythema in the affected area , but
generally without limited range of motion or pain in the hip joint itself . If erythema and warmth are present these findings can signify infection of the bursa (septic bursitis ) , which should be treated with antibiotics . In this patient' s case , an intact sensory examination
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full range of motion of the joint , and focal tenderness in the area of a bursa implicates trochanteric bursitis as the likely diagnosis .
Incorrect Answers : A . B , C . and D.
Hip joint ( Choice A) pain can arise from pathologies such as osteoarthritis , avascular necrosis , synovitis , or septic arthritis. Pathology within the joint would present with pain and tenderness with range of motion of the joint , whereas this patient has normal range of
motion and pain focaliy over the lateral hip .
lnguinai ligament ( Choice B) inflammation is uncommon , however pain in the inguinal region is a frequent presenting complaint . Etiologies of such pain include but are not limited to hernias (inguinal or femoral), ligament and muscle strain and sprain , neuropathic
pain , stress fractures , referred pain , urinary tract infections, renal calculi , and appendicitis . This pain is located in the anterior groin, not in the lateral hip .
Lateral femoral cutaneous neive ( Choice C) is a branch of the lumbosacral plexus and supplies sensation to the ateral thigh . It can become impinged on its course leading to meralgia paresthetica , a condition of pain and paresthesia in its territory.
Sacroiliac joint ( Choice D) pain is experienced in the inferior back and buttocks and may arise from athletic activity or inflammatory disease . ] t genera ly does not refer to the lateral hip.
Educational Objective : Bursae are thin . sac-Jike, fluid-filled structures that reduce friction and permit motion between layers of connective tissue. Trochanteric bursitis presents with pain and swelling of the lateral hip over the greater trochanter. When erythematous
and swollen, infectious bursitis may be present.
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27. A G1-year- old man has had three episodes of painless gross hematuria during the past week. The left flank is mildly tender to palpation . Urinalysis shows blood but no WBCs bacteria, or cellular casts. He says to the physician . 'Tell me like it is . Do I have
;
cancer ? " Which of the following is the most appropriate response?
A ) "Cancer is one of the possible causes of blood in your urine . We will need to perform additional tests to determine the cause ."
B ) "Hematuria can be caused by many things . Trust me. I will let you know if we find anything worrisome . 11
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C ) "It is too soon to tell . Don't worry about that for now . r
D } "Yes, cancer looks likely, but many effective treatments are now available."
E ) "Yes, I'm afraid this usually is due to cancer . Would you like to have someone with you while we discuss it?"
When patients express the desire to be informed about serious diagnoses , physicians should inform patients directly and compassionately. This physician should inform the patient that his hematuria may reflect an underlying cancer but that the diagnosis is not yet
confirmed . Once the patient has been informed that this diagnosis is a possibility, the physician should validate the patients emotions by listening receptively using reflective statements , inferring emotions from the expressed content , and/or normalizing the patients
experience . The physician should also deliver education and explain the next steps using small pieces of information.
Incorrect Answers : B . C , D , and E.
Informing the patient that his diagnosis is unclear ( Choices B and C) would avoid the patient 's question about whether he has cancer . The physician should respond that cancer is a possibility.
Answering the patients question about whether he has cancer with a definitive "yes’ ( Choices D and E) would be premature. Further discussion and treatment planning should occur only after the cancer diagnosis is definitively made.
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Educational Objective : When patients express the desire to be informed about serious diagnoses , physicians should inform pafients directly and compassionately about possible or confirmed diagnoses. The physician should also deliver education and explain the
next steps using small pieces of information.
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28. A 25 -year- old man is brought to the emergency department because of a 2 -hour history of nausea vomiting , abdominal cramping and difficulty passing flatus . Examination of the face shows the lesions in the photograph; similar lesions are seen on the
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fingers and toes. Laboratory studies show hypochromic microcytic anemia . Test of the stool for occult blood is positive . Which of the following is the most likely diagnosis?
A ) Cowden disease
B ) Gardner syndrome
C ) Muir-Torre syndrome
D ) Neurofibromatosis
E ) Peutz-Jeghers syndrome
Correct Answer : E
Peutz-Jeghers syndrome is an autosomai dominant polyposis in which hamartomatous polyps occur in the colon and gastrointestinal ( Gl ) tract , and pigmented macules are found in or around the mouth fips , hands : and genitalia it is associated with increased
, ,
risk for breast and Gl tract cancers (eg , colorectal , stomach small bowel, pancreatic) . Hamartomatous polyps are characterized by disorganized growth of tissue similar to normal native tissue . When solitary, they are usually benign and do not carry a significant
,
risk for malignant transformation, however when syndromic they are associated with increased risk in gastrointestinal tract cancers. Patients with Peutz-Jeghers syndrome may have intestinal obstruction or intussusception as their presenting symptom , such as in
this patient. Polyps can serve as a lead point for intussusception or obstruct the gastrointestinal lumen. Polyps can also cause chronic occult bleeding, leading to a hypochromic microcytic anemia .
Incorrect Answers : A . B . C, and 0.
Cowden disease (Choice A) is an autosomal dominant polyposis associated with hamartomatous pofyps in the Gl tract . It is associated with mucocutaneous neuromas , oral papillomas and cutaneous trichilemmomas.
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Gardner syndrome ( Choice B) is a familial adenomatous polyposis characterized by the presence of thousands of adenomatous polyps arising after puberty it is associated with osteomas , soft tissue tumors supernumerary teeth and hypertrophy of the retinal
, , ,
pigment epithelium .
Muir -Torre syndrome ( Choice C ) is a form of hereditary nonpolyposis colorectal cancer. Affected individuals are prone to developing colon , genitourinary, or skin cancers. Cutaneous manifestations can include keratoacanthomas and sebaceous gland tumors
Neurofibromatosis ( Choice D ) type 1 is a heritable neurocutaneous disorder that presents with cutaneous neurofibromas (benign neoplasms derived from neural crest cells ) , cafe au lait spots , pigmented iris hamartomas (Lisch nodules ) , optic gliomas , and
pheochromocytomas. This autosomal dominant disorder results from a de novo or inherited mutated NF1 tumor suppressor gene.
Educational Objective : Peutz- Jeghers syndrome is an autosomal dominant syndrome that is characterized by hamartomatous polyps in the colon and Gl: tract, and pigmented macules in the mouth , lips, hands, and genitalia . Hamartomatous polyps in the Gl tract
can present with intussusception , bowel obstruction and hypochromic microcytic anemia .
,
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29. A 36-year- old man with a 4- year history of HIV infection conies to the physician for a follow- up examination . Current medications include lopinavir -ritonavir and lamivudine { 3TC )-zidovudine (AZT ). His CD 4+ T-lymphocyte count is 410/ mm 3 (N> 500) ; 6
months ago , it was 720/mm 3 Reverse transcriptase polymerase chain reaction test results show that his remaining CD 4+- T lymphocytes are positive for CCR5. Based on the expression of CCR 5. which of the following cell types in this patient is most likely
also infected with HIV?
A ) B lymphocytes
B ) Eosinophils
C ) Macrophages
D ) Mast cells
E ) Natural killer cells
Macrophages are the other cell type In addition to CD 4+- T lymphocytes that are most likely also infected with HIV as they possess CD 4 and CCR5 on their cell surface . To enter the cell, HIV must first bind to CD 4 via the HIV gp 12D and gp 41 subunits . This binding
induces a conformational change in the HIV envelope allowing for binding to a coreceptor such as CCR5 or CXCR 4. CCR5 is expressed on the surfaces of antigen presenting cells such as macrophages and dendritic cells, in addition to T lymphocytes. Following
this , the HIV envelope fuses with the cellular membrane and expels its contents into the host cell . The HIV RNA genome is subsequently reverse transcribed intg DNAand inserted into the host cell genome via HIV integrase , followed by transcription of HIV genes
and translation into HIV proteins. These proteins are packaged and cleaved to form the mature HIV virus . Following infection with HIV. macrophages may also may serve to perpetuate infection for several reasons : they are present in high numbers at sites of viral
entry, are resistant to the cytotoxic effects of HIV infection allowing for HIV persistence and replication , and have a remarkably long life span withlhe ability to survive far months to years in peripheral tissues. They also distribute widely throughout the body, including
the central nervous system .
Incorrect Answers : A . B . D , and E.
B lymphocytes ( Choice A) , eosinophils ( Choice BY mast ce: ls ( Choice Di and natural killer cells ( Choice E ) do not express both CD 4 and CCR 5 on their surface , thus HIV is unable to enter and infect these cell types.
Educational Objective : HIV binds to CD 4 and a coreceptor such as CCR 5 to enter CD 4+ T lymphocytes . Macrophages also possess CD 4 and CCRb: which allows for HIV viral entry infection can persist given the long half-life of macrophages , their resistance to the
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cytotoxic effects of HIV, and their wide dissemination within tissues.
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30 . A 12 -year- old girl is brought to the physician by her mother after the dentist found many unerupted and supernumerary teeth . Physical examination shows frontal bossing hypertelorism , and retained deciduous teeth. When prompted , the patient is able to
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place her shoulders together anteriorly. Serum studies show a decreased alkaline phosphatase activity. A chest x-ray shows hypoplasia of the clavicles . Skull x-rays show open sutures and multiple Wormian bones . Genetic testing shows a mutation in the
CBFA 1 gene. Which of the following cell types is directly affected by the mutation in this patient?
A ) Chondroblasts
B ) Ghondroclasts
C ) Chondrocytes
D ) Osteoblasts
E ) Osteoclasts
F ) Osteocytes
Osteoblast differentiation is likely impaired in this patient with a physical presentation concerning for cleidocranial dysplasia ( CCD) . CCD is inherited either de novo or in an autosomal dominant manner and presents with bony dysplasia . Diminution or absence of the
clavicle permits abnormal movement of the shoulders anteriorly as seen in this patient . Additional symptoms include impaired skull development , often involving the frontal or parietal bones , the presence of Wormian (intrasutural ) bones , supernumerary teeth
hypoplasia of the maxilla , frontal bossing , hypertelorism , and delayed ossification of the pubic symphysis . CBFA 1 (core binding factor activity 1) gene may be mutated . This gene codes for a transcription factor involved in osteoblast differentiation. Membranous
bone, often found along the midline , is most commonly affected . The life expectancy of affected patients is generally normal, as is neurologic development .
Incorrect Answers : A, B . C . E. and F.
Chondroblasts ( Choice A) , chondroclasts ( Choice B) , and chondrocytes ( Choice C) are the primary cell types involved in the synthesis ( -blast) and breakdown (-clast ) of cartilage . In pathology, chondroblastoma can result from the oversynthesis of cartilage from
chondroblast stimulation. They are not involved in the pathophysiology of CCD, which results from impaired osteoblast differentiation as opposed to imbalanced synthesis or breakdown of cartilage.
Osteoclasts ( Choice E) are the primary cell type involved in the degradation of bone. Excess osteoclast activation results in loss of bone mineral density and weakened bone , as seen in multiple myeloma and Paget disease .
Osteocytes ( Choice F) are the primary cell type found within bone. They are mesenchymal cell derivatives , related to osteoblasts. Reduced numbers of osteocytes would be expected in CCD . but the pathology of CCD occurs upstream at the level of osteoblast
differenfiation .
Educational Objective: i he CBFA1 gene mutation in cleidocranial dysplasia results in impaired osteoblast differentiation with resultant impaired ossification in membranous bone . Features include frontal bossing, facial bone malformations supernumerary teeth , and
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absent or diminutive clavicles .
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31. The table reports survival of patients who had an operation for a particular form of cancer:
Number of Patients at the Number of Patients Who Percent of Patients
Interval Beginning of the Interval Died During the interval Surviving This Interval
0-1 year 500 100 80
1 -2 years 400 50 87.5
2 -3 years 350 35 90
3 -4 years 315 31 90
Which of the following is the probability of a patient surviving 4 years ?
A ) ( . 875 - . 30) x . 90 x . 90
B ) . 375
C ) . 00
D ) . 30 x . 875 x .90 x . 90
E ) ( . 875 - . 30) x . 00
A survival analysis is used to convey the fraction of a group of patients who are alive at a given time point after an intervention has been made. Graphically, this is often done with a Kaplan -IVteier survival curve , the data for which is shown in the tab e. For this
particular cancer the time interval of 0 to 1 year is accompanied by a 20% death rate, or 30% survival rate . This means that if 100 patients were given the same diagnosis and treated with the same operation SO of them would be living at one year. After surviving to
1 year there is then a likelihood of 37.5% that they would survive to 2 years, and so on . This analysis allows prognostication for a patient newly diagnosed with this cancer when that patient 's outcome is yet unknown. The probability that a patient with a new
diagnosis who undergoes treatment survives until 4 years is the combined probability of surviving until 1 year then 2 years , then 3 years , and finally 4 years. This is represented by 0.80i0.375 x 0.00 x 0.90.
Incorrect Answers : A, 6 , C, and E.
Calculating the 4 -year survival rate does not require calculating the difference between two probabilities . Neither ( . 375 - . 80) x . 00 x . 90 ( Choice A) nor (. 875 - . 30) x . 90 ( Choice E) will correctly calcu ate the combined probability of survival through all four years .
.375 ( Choice B) is the survival rate of patients between the 131 and 2 nd year after diagnosis ft does not take into account the probability of the first , third or fourth years . Likewise , . 00 (Choice C) is the survival rate of patients between either the 2 nd and 3 rd year or 3 rd
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and 4ihyear after diagnosis . The probability of surviving from diagnosis to the end of the fourth year is the product of the probabilities of surviving each year.
Educational Objective: Kaptan-Meier estimates are used to provide prognostic data to patients with new diagnoses. The survival rate is the percentage of patients who survive a given time interval. The probability that a patient with a new diagnosis who undergoes
treatment survives until 4 years is the combined probability of surviving until 1 year, then 2 years , then 3 years , and finally 4 years.
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32 . A 45 -year- old man is admitted to the hospital because of congestive heart failure . Two first- degree relatives died in their 40 s with dilated cardiomyopathy and cirrhosis . Physical examination shows cardiac enlargement and generalized hyperpigmentation .
His serum glucose concentration is 320 mg/dL. Histologic examination of endomyocardial tissue is most likely to show an excess of which of the following?
A ) Amyloid
B ) a rAntitrypsin
C ) Cerebroside
D ) Copper
E ) Eosinophils
F ) Iron
G ) Lysosomal glycogen
H ) Mucopolysaccharide
Correct Answer : F.
Iron deposition will most likely be appreciated on histologic examination of endomyocardial tissue in this patient with a probable diagnosis of hemochromatosis . Hemochromatosis may be acquired or inherited secondary to mutations in the HFE gene , leading to
abnormally increased intestinal absorption of iron . This results in accumulation of iron in the body increased serum iron: and increased ferritin iron can accumulate in several organs , including the liver, pancreas , skin , heart , and joints. Because of increased free
; ,
radical generation and oxidative damage , hemochromatosis can manifest with failure of the affected organs. It typically presents after decades of iron accumulation with tiver failure manifest as cirrhosis and portal hypertension , diabetes meilitus , arthritis
secondary to calcium pyrophosphate deposition , cardiomyopathy with resultant symptoms of heart failure , darkening of the skin and gonadal atrophy. Hemochromatosis , when acquired, may occur in the setting of transfusion-dependent anemias such as
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thalassemia , but family history of similar symptoms makes hereditary hemochromatosis more likely in this patient. Diagnostic studies may include biopsy, which commonly shows iron deposition on Prussian blue stain . Treatment involves serial phlebotomy and
management of secondary disorders such as heart failure and diabetes meilitus .
Incorrect Answers : A, B . C . D , E . G , and H.
Amyloid ( Choice A ) deposition is seen in patients with amyloidosis , a disorder in which low molecular weight proteins deposit in tissues and cause organ dysfunction . These proteins are often immunoglobulin light chains . Amyloidosis can cause restrictive
cardiomyopathy. Cirrhosis may occur but bronzing of the skin and diabetes meilitus are more consistent with hemochromatosis .
a 1-Antitrypsin (Choice B) deficiency results in fiver disease and emphysema , especially in individuals who smoke . Diabetes meilitus and hyperpigmentation are less common .
Cerebroside ( Choice C } deposition is seen iin metachromatic leukodystrophy which is caused most commonly by deficiency of arylsulfatase A , resulting in abnormal accumulation of cerebroside sulfate in the central and peripheral nervous systems .
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Copper ( Choice D) deposition occurs in Wilson disease . Patients present with liver dysfunction and neuropsychological impairment ( eg. parkinsonism , ataxia, tremors, dystonia , dementia hallucinations , and/or personality changes) .
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Eosinophils ( Choice E) can be found in organs in numerous disease states . One example is eosinophilic esophagitis, which presents commonly with food impaction . Biopsy shows eosinophils infiltrating the esophageal mucosa . Eosinophils also play a primary
role in various hypereosinophilic syndromes , related to the site of eosinophil deposition including myocarditis or colitis .
Lysosomal glycogen ( Choice G) deposits are found in glycogen storage diseases . One example is Pompe disease , which leads to accumulation of glycogen in the lysosomes with findings of cardiomega y, cardiomyopathy, hepatomegaly, and hypotonia .
Mucopolysaccharide ( Choice H ) deposition is a feature of mucopolysaccharidoses. One example is mucopolysaccharidosis I (Hurler syndrome) , which results from deficiency of the enzyme a - L - iduronidase , with subsequent lysosoma: accumulation of
glycosaminoglycans ( eg . heparin sulfate and dermatan sulfate ) . It is an autosoma! recessive disease and presents with physical features such as coarse facial features with a large elongated face , widely spaced orbits , corneal opacification , and
,
hepatosplenomegaly.
Educational Objective : Hemochromatosis presents with liver failure, diabetes meilitus , arthritis , heart failure , darkening of the skin , and gonadal atrophy secondary to excess total body iron. Biopsy commonly shows excess iron on Prussian blue stain inherited
,
hemochromatosis is the result of abnormally increased intestinal absorption of iron, while acquired forms are often the result of chronic blood transfusions .
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33. A study is conducted to assess the effectiveness of a registry for identifying patients 50 years old and older eligible for colon cancer screening . Medical practices are selected based on equal and proportional representation of both genders and
socioeconomic and ethnic groups : including those who have medical insurance and those who do not . Half of the practices will use the registry for a 15- year period and the other half will provide usual care without the registry during the same period .
Results show that the colon cancer mortality rate is decreased in the practices using the registry, and the researchers recommend use of a patient registry to decrease the number of deaths due to colon cancer. Which of the following study characteristics
most directly supports the researchers" recommendation?
A ) Accuracy
B ) External validity
C ) Face validity
D ) Precision
E ) Reliability
External validity determines whether an experiment can be generalized and its conclusions applied to groups beyond those considered in the study population . In other words , will the conclusions hold for different populations at different times ? In this example, a
registry that identifies patients over age 5 Q : but then broadly selects practices for inclusion that have representation of gender socioeconomic and ethnic breadth , and wide financial and insurance status will likely capture a reasonable sample of the population as a
whole presenting to medical practices . The study period was also quite long , 15 years, which is likely sufficiently long to capture outcomes related to colorectal carcinoma , a condition with a long latency period . Given that the study showed reduced mortality rate
through the use of the registry, the researchers make the recommendation to use it broadly, a recommendation based on proximate similarity of practices that will use it . In other words , the study results should apply to many medical practices beyond those purely
with the characteristics of those included .
Incorrect Answers : A, C D . and E.

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Accuracy ( Choice A) describes the absence of error or bias and reflects how correct the test measurements are as compared to actuality. In other words if a patient actually weighs 50 kg and the test measures the patient' s weight , wilt the test show a weight of 50
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kg? If so , the test may be considered accurate.
Face validity ( Choice C ) is a relatively weak form of a validity assessment that subjectively asks whether the test or experiment measures what it is supposed to measure . In other words , is the test suitable to its aims ? This experiment appears to be valid at face
value - it is designed to measure whether a registry will reduce the mortality from colorectal carcinoma and compares its use over a long time across medical practices.
Precision ( Choice D ) describes the reproducibility of results . In other words , how reliable is the test? More precise measurements suffer from less variation in measurement . Decreasing random error in a test increases precision. If a patient actually weighs 50 kg .
and the test measures the patient ' s weight will the test show a weight of 50 kg each time? If so . the test may be considered precise. Reliability ( Choice E ) is a related concept to precision that describes the consistency and reproducibility of results. A reliable test wifi
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yield the same , precise result each time .
Educational Objective: External validity determines whether an experiment can be generalized , and its conclusions applied to groups beyond those considered in the study population .
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34 . During a study, a healthy 35 -year- old woman and a 35 -year - old woman with Crohn disease are given an oral solution of radiolabeled lactulose. The appearance of radioactivity in their urine is monitored over the next 24 hours. Urinary excretion of
radioactivity in the patient with Crohn disease is much greater than that of the healthy subject . This finding is most likely due to inflammation-associated changes in the integrity of which of the following epithelial structures?
A ) Adherens junctions (zonulae adherentes)

B ) Basement membrane
C ) Desmosomes { maculae adherentes )
D ) Gap junctions
E ) Tight junctions (zonulae occfudentes )
Correct Answer : E
Tight junctions (zonulae occludentes ) are a type of epithelial cell connection composed of proteins called claudins and occludins Tight junctions are located between two celis: toward the apical surface , and create a watertight seal to prevent the paracelMar
movement of solutes or water through an epithelial or endothelial lining . Inflammation of an epithelial lining causes it to become more permeable to substances via impairment of tight junctions . As seen in this patient with Crohn disease , inflammation of the wall of
the small intestine impairs tight junctions and allows substances which would not normally be absorbed by the enterocytes to be transmitted paracellularly and then diffuse into the interstitial blood vessels . Another example of this same phenomenon is seen in an
exudative pleural effusion . Inflammation from pneumonia for example , impairs tight junctions and allows for solutes to move paracellularly from the intravascular space or alveoli into the pleura! space. The lack of tight junctions explains the movement of large
,
molecules which could not normally diffuse across cells .
Incorrect Answers : A . B C . and D.

(
Adherens junctions (zonulae adherentes) ( Choice A ) are epithelial cell junctions which connect the actin cytoskeletons of adjacent cells to each other . A defect in adherens junctions such as when E -cadherin expression is lost in breast cancer allows for cells to
, ,
metastasize .
Basement membrane ( Choice B) is a barrier which separates an epithelial lining from the interstitial tissue surrounding it . For example , the basement membrane separates the epidermis from the dermis in the skin . The basement membrane is made of type IV
collagen, laminin , heparan sulfate , and fibronectin among other molecules . Type IV collagen is defective in Alport syndrome causing dysfunction of the glomerular basement membrane .
,
Desmosomes (maculae adherentes ) ( Choice C) are a second protein complex which maintain ceil-to- cell adhesion in the epidermis by connecting the cytokeratin skeleton of two adjacent cells . Pemphigus vulgaris is caused by antibodies to desmosomes and
presents with fragile , flaccid blisters.
Gap junctions ( Choice D ) are connections between the cytoplasm of two adjacent cells that allow for the movement of small molecules in either direction . They are made of channel proteins called connexins . They play a role in allowing a chemical or electrical signal
to transfer between cells, such as cardiac myocytes.
Educational Objective: Epithelial cell connections include tight junctions , adherens junctions desmosomes . and gap junctions Tight junctions are responsible for creating a tight seal to prevent the paracellular movement of solutes or water through an epithelial or
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endothelial lining . Inflammation often impairs the efficacy of tight junctions .
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35. A physician prescribes a recently marketed drug for 20 patients . After several months: five patients develop increased serum AST and ALT activities and show clinical symptoms of hepatotoxicity. The physician discontinues the drug for all patients and
reports the adverse effects to the FDA . The physician has participated in which of the following phases of clinical drug testing?
A ) Phase 1
B ) Phase 2
C ) Phase 3
D ) Phase 4
Clinical trials are an important aspect of the development of any new pharmaceutical or intervention. They involve the experimental study on human subjects and compare a new treatment against a placebo or an alternative treatment . The FDA regulates trials for
newly developed drugs and a series of phases must be undertaken to demonstrate safety efficacy, comparability to standard of care , and ong -term adverse effects . In this example a drug that lias been recently marketed ; s prescribed to 20 patients , 25% of whom
,
show signs of hepatotoxicity after several months . The action of reporting this to the FDA describes the physician participating in Phase 4 of the drug trial, which is characterized by post-distribution and post-prescription surveillance fallowing treatment approval .
Long-term adverse effects and rare adverse effects or outcomes are often identified this way, and failure of a drug during Phase 4 can result in discontinuation/ withdrawal of the drug from the markets and loss of approval by the FDA .
Incorrect Answers : A . B . and C .
Phase 1 ( Choice A ) is the initial phase of a clinical trial . In this phase , a small number of volunteers receive the treatment , and data is collected to gauge safety and toxicity adverse effects , interactions , pharmacodynamics, and pharmacokinetics . I he volunteers in
,
this stage are healthy. Failure at this stage limits further progress of the trial, as the intervention is deemed unsafe for human use.
Phase 2 ( Choice B) involves the trial of the intervention on patients who have the disease to be treated. As in Phase 1, a small number of volunteers are involved in this phase. Efficacy is assessed in this phase along with dosing . Continued study of safety and
adverse effects occurs .
Phase 3 ( Choice C ) involves the conduction of a larger randomized controlled trial once safety and efficacy have been established as in Phases 1 and 2 . In this phase patients are assigned , ideally via a randomized , blinded process , to the treatment or placebo ( or
, ,
standard of care ) arm of a trial . In this manner , whether the new intervention is equivalent to , better than , or worse than the control is assessed . Approval at this stage can lead to marketing of the drug and commercial use .
Educational Objective: Clinical trials occur in phases . Phase 1 assesses safety in healthy volunteers . Phase 2 assesses efficacy in a small: number of sick volunteers . Phase 3 is generally a. large , randomized trial comparing the new intervention to placebo or the
previous standard , and Phase 4 describes post-marketing surveillance for long-term and rare effects .
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36. A 27 -year- old man who is a weight]ifter comes to the physician for a routine examination. He has been taking a synthetic androgen for the past year to increase his muscle mass . Examination shows increased scalp hair loss and mild testicular atrophy.
Which of the following is most likely responsible for the decreased size of this patient's testicles ?
A ) Compression of the testes by overdeveloped pelvic muscles

B ) Downreguiation of pituitary luteinizing hormone receptors
C ) Downreguiation of testicular follicle- stimulating hormone receptors
D } Increased secretion of inhibin
E ) Increased negative feedback or gonadotropin secretion
F ) Increased sexua: activity
Correct Answer : E
Excessive circulating androgen concentrations :n the setting of the exogenous use of synthetic androgens results in increased negative feedback on gonadotropin secretion . Testosterone provides negative feedback upon gonadotropin releasing hormone (GnRH)
neurons in the hypothalamus , with subsequent decreases in the release of luteinizing hormone ( LH) and of follicle -stimulating hormone (FSH ) by the anterior pituitary . Downreguiation of LH secretion results in decreased stimulus for the testicular production of
testosterone, which leads to testicular atrophy. Testicular atrophy may commonly occur in patients who are taking anabolic steroids or in patients who are taking testosterone replacement therapy.
Incorrect Answers : A . B C . Dr and F.

(
Compression of the testes by overdeveloped pelvic muscles ( Choice A) would not occur The testes are located within the scrotum , outside of the pelvis and are not vulnerable to compression by pelvic muscie hypertrophy.
,
Downreguiation of pituitary luteinizing hormone receptors ( Choice 6 ) would not cause testicular atrophy. The LH receptor is responsible for the transduction of LH- dependent signaling that causes the synthesis of androgens and is primarily located in gonadal tissue .
Downreguiation of LH receptors in gonadal tissue wi I lead to testicular atrophy. LH receptor is not expressed in substantial quantities in extragonadal tissues .
Downreguiation of testicular follicle- stimulating hormone receptors ( Choice C ) leads to decreased spermatogenesis . In the testis. FSH receptors are primarily expressed on Sertoli cells. Testicu ar atrophy is primarily mediated by the inhibition of LH signaling rafher
,
than that of FSH.
Increased secretion of inhibin ( Choice D) is performed by Sertoli ce : s and provides negative feedback upon the anterior pituitary to decrease FSH secretion . Increased secretion of inhibin would not result in changes in testosterone production by the testis and
would not lead to testicular atrophy.
Increased sexual activity (Choice F ) does not lead to atrophy or hypertrophy of the testes
Educational Objective: Testicular atrophy is primarily caused by decreased testicular testosterone synthesis as a result of the absence of stimulation by luteinizing hormone. This commonly occurs in the setting of anabolic steroid use or testosterone replacement
therapy, as these exogenous androgens provide excessive negative feedback upon the hypothalamus , thereby causing the decreased production of GnRH and , subsequently. LH .
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37. A 51-year- old man develops diaphoresis tachycardia and a blood pressure of 155/ 100 mm Hg 24 hours after undergoing an abdominal operation. Two hours later , he has a generalized tonic-cEonic seizure . Which of the following i;s most likely responsible
, ,
for these adverse effects in this patient?
A ) Acute renal failure

B ) Alcohol withdrawal
C ) Anaphylactic reaction
D } Narcotic pain medication
E ) Sepsis from a gram-positive organism
Alcohol withdrawal typically leads to sympathetic overdrive and: in severe cases : generalized seizures . Chronic alcohol use causes changes in the expression of different subunits of the /V-methyl-d -aspartate (NMDA) and gamma- aminobutyric add ( GABA )
receptors . As a result of these adaptations, the discontinuation of alcohol ieads to sympathetic overdrive. Initially, this hyperexcitataitity results in tremors: anxiety, diaphoresis , hypertension tachycardia, and nausea. Within hours of the last drink , alcoholic
,
hallucinosis (auditory or visual hallucinations without confusion or autonomic instability) and seizures (caused by cortical hyperactivity) can occur Delirium tremens , the most concerning and life -threatening complication of alcohol withdrawal, involves severe
confusion, disorientation, fluctuations in consciousness, agitation , visual hallucinations , and autonomic instability (fluctuations in pulse and blood pressure with hyperthermia).
Incorrect Answers : A . C , D and E.

;
Acute renal failure ( Choice A ) can lead to oliguria and may be associated with hyperkalemia , metabolic acidosis and uremia . None of these changes typically cause seizures . Additionally, sympathetic overactivation would be uncommon .
,
An anaphylactic reaction (Choice C) is an acute , life-threatening reaction to an allergen that leads to systemic mast cel degranulation . Anaphy actic reactions typically present with hypotension caused by increased vascular permeability from histamine . Furthermore ,
a seizure would be atypical in the presentation of an anaphylactic reaction .
Narcotic pain medications (Choice D) cause symptoms of central nervous system depression including sedation, respiratory depression, bradycardia , and hypotension as opposed to this patient ' s tachycardia and hypertension .
Sepsis from a gram -positive organism ( Choice E ) typically causes hypotension . Additionally, gram-positive or gram-negative bacterial infections may occur in the setting of an abdominal wound ; however, these infections do not typically develop until several days
postoperatively. A seizure would be atypical.
Educational Objective : Alcohol withdrawal is associated with sympathetic overdrive and initially presents with tremors , anxiety, diaphoresis hypertension, and tachycardia . In severe alcohol withdrawal, seizures and delirium tremens may occur.
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38. A G 2 -year- old man is brought to the physician by his wife because of increasing confusion during the past 6 months . His wife says that he has become lost twice in the past month when going to work, even though he has been going to the same office for
12 years. She adds that he often has difficulty finding objects such as his glasses and keys sometimes cannot recall his grandchildren's names , and has become very critical of her cooking which he used to enjoy. When asked he can name only the
,
;
current president and none of the candidates for an upcoming presidential election, although he and his wife watch the television news together each night . Neurologic examination shows no motor or sensory abnormalities . His Mini - Mental State
Examination score is 19/30. Treatment with a cholinesterase inhibitor is most likefy to improve this patient’s memory because of its ability to target synaptic connections between which of the following structures ?
A ) The basal forebrain and neurons in the cerebral cortex

B ) The dentate nucleus and the thalamus
C ) The fornix and neurons in the mammillary bodies
D ) The substantia nigra and the neurons of the globus palfidus
E ) The thalamus and neurons in layer 4 of the cerebral cortex
Dementia: Alzheimer type , results from decreased cholinergic signaling in the cerebral cortex and basal forebrain . Cholinergic neurons (which primarily originate from the locus coeruleus and basal forebrain) project widely to areas including the cortex , mediating
attention , learning , and memory. Alzheimer dementia is the most prevalent type of dementia , presenting with progressive cognitive decline that begins with short-term memory impairment , progresses to apraxia and language abnormalities and culminates in
,
behavioral and personality changes preventing the patient from performing basic activities of daily living . Acetylcholinesterase normally hydrolyzes acetylcholine in synaptic clefts. Donepezil and other cho inesterase inhibitors non-competitively and reversibly inhibit
acetylcholinesterase activity and thereby increase the amount of synaptic acetylcholine available for neurotransmission. Though these medications may slow the rate of cognitive decline and modestly improve functionality, they are no: curative.
Incorrect Answers : B . C, D , and E.
The dentate nucleus and thalamus ( Choice B ) med; ate output from the cerebellum. These structures are not typically affected in Alzheimer dementia .
The fornix and neurons in the mammillary bodies ( Choice C ) constitute output pathways from the hippocampus and mediate episodic memory. Lesions may result in amnesia . Patients with Alzheimer dementia demonstrate hippocampal atrophy and decreased
cholinergic signaling in the hippocampus, but the fornix and mammillary bodies are less commonly affected.
The substantia nigra and the neurons of the globus palfidus ( Choice D ) together modulate voluntary movement . These brain regions are affected in Parkinson disease , not Alzheimer dementia.
The thalamus and neurons in layer 4 of the cerebral cortex ( Choice E ) mediate the transmission of sensory information to the primary sensory cortices . Sensory domains are not significantly affected in Alzheimer dementia .
Educational Objective : Dementia , Alzheimer type , results from decreased cholinergic signaling in the cortex and basal forebrain . Alzheimer dementia is the most prevalent type of dementia, presenting with progressive cognitive decline that culminates in the inability
to perform basic activities of daily living.
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39. A 21-year- old woman who is a college student comes to the physician because of a severe left-sided headache , nausea and vomiting for 1 hour. Her symptoms began with flashing lights in both eyes while she was studying for final exams . Physical
,
examination shows no abnormalities . The most appropriate treatment is a drug that acts on a receptor for which of the following endogenous mediators ?
A) p -Endorphin
B ) Histamine
C ) Neuropeptide Y
D ) Nitric oxide
E ) Serotonin
Correct Answer : E
This patient with a migraine headache may be treated with triptan medications , which are serotonin agonists . Migraine is a relatively common condition that presents with recurrent primary headaches . Migraine headaches are typically severe, unilateral, throbbing ,
and associated with nausea, photophobia , and phonophobia . Some patients additionally experience an aura before or during the headache , which may present with vision loss followed by the perception of scintillating shapes or lines and / or paresthesias. Migraine
triggers include stress, menstruation , weather changes , fasting , and alconol. Migraines are postulated to arise from deficient serotonin inhibition of descending pain pathways. Acute migraine treatment includes triptans (serotonin agonists), dopamine antagonists ,
antiemetics , acetaminophen , and/or nonsteroidal anti-inflammatory drugs (NSAIDs ) . For patients with disabling or frequent migraines , prophylactic treatment is also recommended and includes p -adrenergic blockers , antidepressants (such as tricyclic
antidepressants and serotonin-norepinephrine reuptake inhibitors), and anticonvulsants.
Incorrect Answers : A . B , C . and D.
(3-Endorphin ( Choice A ) is an endogenous opioid that is released during intense exercise and stress . Opioid medications mimic endogenous (3-endorphin but are not recommended for migraines because of the risk for opioid overuse and the potentially resultant
worsening of headaches.
Histamine ( Choice B) release causes vasodilation and increased vascular permeability and contributes to environmental allergies . Antihistaminergic medications ( eg . diphenhydramine , cetirizine ) are utilized to address allergies and are used off-label to treat anxiety
and insomnia . Antihistaminergic medication does not necessarily play a rote in acute migraine treatment , however the anticholinergic and sedating effects of first-generation antihistamines can counteract adverse effects of dopamine antagonists (eg , akathisia ,
dysfonia) and improve patient comfort .
Neuropeptide Y ( Choice C ) is an orexigenic peptide neurotransmitter that modulates peripheral sympathetic transmission . Neuropeptide Y is not involved in migraine pathogenesis or treatment .
Nitric oxide ( Choice D) is a signaling molecule that modulates synaptic plasticity and promotes vasodilation . Nitric oxide is not involved in migraine pathogenesis or treatment .
Educational Objective: Migraines are typically unilateral , pulsating headaches that are associated with nausea, photophobia , and phonophobia and may also present with visual or sensory auras. Acute migraine treatment includes triptans , which are serotonin
agonists.
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40 . A 16 -year- old boy is brought to the emergency department 30 minutes after he dove into a 3-foot-deep swimming pool at night . On examination , he is unable to move the right upper and lower extremities . The most likely cause of the movement deficits in
this patient is damage to which of the following labeled regions in the photograph of a cross section of the spinal cord shown?
A)
B)
C)
D)
E)
F)
G)
H)
Correct Answer : E
Label E represents the right lateral corticospinal tract in this cervical spinal cord section (as indicated by the ovoid shape and predominance of white matter). Upper motor neurons of the corticospinal tract originate in the primary motor cortex , descend ipsilaterally
through the internal capsule and midbrain , decussate in the caudal medulla , and then descend contralaterally in the spina] cord to synapse with the contralateral lower motor neuron. Since the decussation occurs superior to the cervical spinal cord , lesions
involving the lateral corticospinal tract within the cervical spinal cord will iead to ipsilateral motor weakness and an upper motor neuron pattern of dysfunction ( eg , increased muscle tone , hyperreflexia, Babinski reflex ). Traumatic spinal cord injuries can occur
through diverse mechanisms such as cord compression by a vertebral column fracture . Given this patient ' s hemiparesis of the right upper and lower extremities the location of the injury was likely at the C 5 level or higher.
,
Incorrect Answers : A . B C . D. F: G: and H .

(
Labels A and D represent the fasciculi cuneatus of the dorsal column-medial lemniscus tract , while labels B and C represent the fasciculi gracilis of the dorsal column -medial lemniscus tract . The dorsal column-medial lemniscus tract decussates in the medulla .
Dorsal column-medial lemniscus tract lesions within the cervical spinal cord iead to ipsilateral deficits in pressure , vibration fine touch, and proprioception . The fasciculi gracilis contain these sensory fibers for the lower body while the fasciculi cuneatus contain
,
these sensory fibers for the upper body.
Label F represents the left lateral corticospinal tract. Lesions in this location would result in an upper motor neuron pattern of dysfunction in the left upper and/or lower extremities .
Labels G and H represent the spinothalamic tracts which carry fibers that mediate pain, temperature , crude touch , and pressure sensation . Lesions of the spinothalamic tracts in the cervical spinal cord would lead to deficits in these sensory domains in the
contralateral extremities . This occurs because of the decussation of the tract across the anterior white commissure immediately after the peripheral sensory nerve synapses with the second order neuron in the ipsilateral dorsal horn of the spinal cord.
Educational Objective: Upper motor neurons of the corticospinal tract decussate in the caudal medulla . Lesions of the lateral corticospinal tract in the cervical spinal cord lead to an upper motor neuron pattern of dysfunction in the ipsilateral extremities .
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41. An 88-year -old man foses consciousness when his neck is palpated during a routine health maintenance examination. He has a 40 -year history of hypertension that has been well controlled with hydrochlorothiazide and a 20 -year history of degenerative
osteoarthritis: for which he occasionally takes anti- inflammatory drugs. Which of the following is the most likely cause of the syncope ?
A ) Complete heart block

B ) Laryngospasm
C ) Peripheral arteriole constriction
D ) Peripheral arteriole dilation
E ) Sinus bradyarrhythmia
F ) Ventricular tachyarrhythmia
Correct Answer : E
Carotid sinus syndrome is characterized by an exaggerated response to carotid baroreceptor stimulation with resultant sinus bradycardia : hypotension and syncope . Baroreceptors located at the carotid bifurcations and the aortic arch are important in regulating
, ,
cardiac output and maintaining adequate perfusion pressures to the brain and organs of the upper body. Baroreceptors are sensitive to mechanical pressure : normally: an increase in blood pressure stimulates baroreceptor activity, which activates a reflex arc
resulting in parasympathetic innervation of the sinoatrial and atrioventricular nodes and inhibition of sympathetic vascular tone . This results in decreased pulse and peripheral vascular resistance. Mechanical compression of the baroreceptors from external palpation
can stimulate this reflex , which may be exacerbated in the setting of volume depletion , such as the presented case where the patient is taking a thiazide diuretic.
Incorrect Answers : A, B . C, D . and F.
Complete heart block (Choice A) , also called third - degree atrioventricular block, occurs when no sinus impulses are transmitted through the AV conduction pathway, resulting in complete dissociation between the P waves and the GRS complexes . Patients usually
require a pacemaker. The temporal association with neck palpation in this patient is more suggestive of carotid sinus syndrome and sinus bradyarrhythmia.
Laryngospasm ( Choice B) . s an exaggerated protective airway reflex to prevent aspiration that can result in partial or complete airway obstruction It typically presents with acute dyspnea increased work of breathing , and may result in hypoxemia -induced
,
bradycardia.
Peripheral arteriole constriction ( Choice C ) occurs with increased sympathetic activity and signaling at vascular adrenergic receptor sites , resulting in an increase in blood pressure. It does not lead to syncope .
Peripheral arteriole dilation (Choice D) does result from carotid sinus stimulation. Patients experience orthostatic hypotension with presyncope symptoms such as lightheadedness and tunnel vision .
Ventricular tachyarrhythmia ( Choice F) includes ventricular tachycardia ventricular fibrillation , and ventricular premature beats. Ventricular tachyarrhythmias are potentially life -threatening because of the potential for the sudden Eoss of adequate cardiac output .
,
Educational Objective: The cardiovascular system must adjust to postural changes to maintain adequate perfusion pressure to the head and upper body. Baroreceptors in the carotid sinus and aortic arch detect changes in pressure and stimulate the body 's
response . Carotid baroreceptor hypersensitivity can provoke sinus bradycardia and syncope .
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42 . A 25 -year- old man comes to the physician with his wife because they have been unable to conceive for 2 years. Previous examination of the wife showed no abnormalities . Examination of the patient shows no abnormalities. The patient' s laboratory studies
show autoantibodies to sperm. Dysfunction of which of the following cell types is the most liikeEy cause of these findings?
A ) Leydig cells
B ) Primary spermatocytes
C ) Secondary spermatocytes
D ) Sertoli cells
E ) Type A spermatogonia
In normal male anatomy the Sertoli cells lining the seminiferous tubu es create a blood -testis barrier through tight junctions which allows the seminiferous tubule to exist as an immune -protected site . The spermatozoa developing within the seminiferous tubule
contain genetic material that may be foreign to the body as a result of recombination during meiosts . Thus, when this barrier is intact it prevents potential novel antigens from leaving the seminiferous tubule and encountering the host immune system . If the barrier is
,
disrupted, as may occur in testicular trauma: the spermatozoa can elicit an immune response that may include production of autoantibodies against the gametes . Sperm autoantibodies are a theoretical cause of male infertility. Other causes of male infertility include
Klinefelter syndrome (XXY karyotype causing dysgenesis of the seminiferous tubules and testicular atrophy ), increased testicular temperature ( seen in cryptorchidism or varicocele) , or gonadotropin-releasing hormone (GnRH ) deficiency.

(
Spermatogenesis takes place in the seminiferous tubules of the testes. Pulsatile GnRH produced by the hypothalamus causes the pituitary to secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH) which drive spermatogenesis . LH acts on the
Leydig cells ( Choice A ), ocated adjacent to but outside of the seminiferous tubules , and causes them to secrete testosterone , which is necessary to create the proper hormonal environment within the seminiferous tubule required for spermatogenesis . Dysfunction
of Leydig celts would not damage the blood-testis barrier leading to antibody formation .
Lining the seminiferous tubules are spermatogonia , which generate the primary spermatocytes ( Choice B) that then mature into secondary spermatocytes ( Choice C ) and will ultimately become spermatozoa. So long as the blood-testis barrier is intact , a defect in
either primary or secondary spermatocytes will not induce antibody formation .
Spermatogonia lining the seminiferous tubules are either type A (Choice E) or type B Type A spermatogonia undergo active mitosis and divide to produce type B spermatogonia . The type B spermatogonia progress to become primary spermatocytes . The type A
spermatogonia do not mature , themselves, but continue to divide .
Educational Objective: Without the benefit of the blood -testis barrier the gametes may elicit an immune reaction and production of autoantibodies . This is a theoretical cause of male infertility. Other causes of male infertility include K inefelter syndrome , increased
,
testicular temperature, and gonadotropin-releasing hormone deficiency.
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43. A 28 -year- old woman has had restlessness , exercise intolerance , palpitations diarrhea and excessive sweating for the past 3 days. She had an upper respiratory tract infection 3 weeks ago. The thyroid gland is diffusely enlarged and tender. Serum total
, ,
thyroxine (TJ and total triiodothyronine (T$ concentrations and free T 4 index are increased . Serum thyroid- stimulating hormone concentration and radioactive iodine uptake by the thyroid gland are both decreased . Which of the following is the most ikefy
cause of her condition?
A ) Autoimmune (Hashiimoto) thyroiditis

B ) Diffuse toxic goiter (Graves disease )
C ) Euthyroid sick syndrome
D ) Subacute thyroiditis
E ) Toxic adenoma
F ) Toxic multinodular goiter
Correct Answer D .
This patient' s presenting findings are highly suggestive of subacute granulomatous thyroiditis , also known as de Quervain thyroiditis . Subacute granulomatous thyroiditis is a self-limited inflammatory condition of the thyroid gland that often follows an acute viral
illness. Presenting findings are typically suggestive of clinical hyperthyroidism and may include diaphoresis , palpitations , neck pain dysphagia , fever, tachycardia, increased serum concentrations of T - a n d T 4, and a decreased serum concentration of thyroid-
,
stimulating hormone . Patients may eventually become hypothyroid or euthyroid following the acute inflammatory, hyperthyroid phase . Subacute granulomatous thyroiditis is distinguished from other forms of hyperthyroidism by the presence of a painful tender
thyroid , which is highly suggestive of the diagnosis. It is a so characterized by the absence of iodine uptake on a radionuclide scan, and by the presence of multinucleated giant cells on fine needle aspiration .
incorrect Answers : A . B , C . E , and F.
Autoimmune (Hashimoto) thyroiditis ( Choice A ) is the most common form of thyroiditis and is characterized by the presence of antithyroid peroxidase and antithyroglofculin antibodies . Patients with chronic disease present with signs and symptoms of
hypothyroidism, including fatigue , cold intolerance, weight gain , hyporeflexia , myxedema , and dry, coal skin. While patients in the acute stage of the disease may present with symptoms of hyperthyroidism, the thyroid is not typically painful or tender .
Diffuse toxic goiter (Graves disease ) ( Choice B ) is the most common cause of hyperthyroidism and is caused by an autoantibody that activates thyroid stimulating hormone receptors on the thyroid. It presents with symptoms of hyperthyroidism, pretibial myxedema ,
and thyroid ophthalmopathy, which can cause diplopia, proptosis , and restrictive strabismus. The thyroid is not typically painful or tender.
Euthyroid sick syndrome (Choice C) occurs in the setting of acute systemic illness and is characterized by decreased concentrations of thyroid hormone and a euthyroid clinical appearance. Euthyroid sick syndrome does not present with an enlarged or tender
thyroid .
Toxic adenomas ( Choice E) are a type of hyperfunctioning thyroid follicular adenoma that secrete abnormally high concentrations of thyroid hormone and present with symptoms of hyperthyroidism . They typically present as a solitary nodule which avidly takes up
,
iodine on radionuclide scintigraphy, and are not typically tender .
Toxic multinodular goiter ( Choice F ) is a common cause of hyperthyroidism and is secondary to thyroid hormone- secreting nodules that function independent of thyroid - stimulating hormone . Patients present with symptoms of hyperthyroidism , but the thyroid is not
typically painful or tender.
Educational Objective: Subacute granulomatous thyroiditis, also known as de Quervain thyroiditis , is a self-limited thyroiditis that often follows an acute viral illness and that presents with symptoms of hyperthyroidism. A painful , tender thyroid is highly suggestive of
the diagnosis.
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44 . A 3-month-old boy is brought to the physician because of yellow eyes and skin and weakness since birth . Physical examination shows jaundice , large fontanels a flat midfacial area hypotonia and hepatomegaly. Serum studies show :
, , ,
Total bilirubin (mainly direct) increased

AST increased
ALT increased
Very-long- chain fatty acids increased
A liver biopsy specimen shows foamy lipid-filled hepatocytes necrosis: and absence of a specific organelle . This organelle is most likely which of the following?
,
;
A ) Golgi complex
B ) Lysosomes
C ) Mitochondria
D ) Peroxisomes
E ) Smooth endoplasmic reticulum
Zellweger syndrome is caused by a genetic mutation that leads to an absence of peroxisomes. Peroxisomes synthesize cholesterol and bile acids , as well as cell membrane substrates. As peroxisomes are also responsible for metabolizing very long chain fatty
acids (VLCFA) , phytanic acid: pipecolic acid , pristanic acid hydrogen peroxide , and ethanol, their absence leads to an accumulation of these products. Zellweger syndrome classically presents with seizures , ntellectual disability, hypotonia, hepatomegaly, jaundice
'
, ,
kidney disease cataracts , hearing loss and craniofacial abnormalities. Physical examination will show an absence of reflexes and results of laboratory studies will show increased concentrations ofVLCFA , hepatic transaminases and direct bilirubin, as observed in
, , , ,
this patient . There is no effective treatment, and life expectancy is less than six months of age .
Incorrect Answers : A, 6 , C . and E.
The golgi complex ( Choice A ) sorts modifies and transports proteins within the cell and to the cell membrane for export . Deficiency of the golgi complex in hepafocytes would likely lead to cell death although it would not result in an increased concentration of
, , ,
VLCFAs .
Lysosomes (Choice B } are responsible for the degradation of a variety of substrates including those brought into the cell through endocytosis and materials of the cell itself ( eg , autophagy) . Deficiencies in lysosomal enzymes lead to lysosomal storage disorders ,
,
which present broadly with neurocognitive decline , skeletal abnormalities , and craniofacial abnormalities.
Mitochondria ( Choice C) are responsible for producing energy for the cell in the form of adenosine triphosphate. Disorders of mitochondrial structure or function include MELAS ( mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome
and myoclonic epilepsy with ragged red fibers. Complete absence in the hepafocytes would lead to cei death and liver failure .
The smooth endoplasmic reticulum ( Choice E) is responsible for synthesizing lipids and steroids as well as detoxifying toxins While not present in erythrocytes their absence in hepatocytes would likely lead to cell death and liver failure , although it would not result
, ,
in an increased concentration of VLCFAs .
Educational Objective: Zellweger syndrome is caused by a genetic absence of peroxisomes , and presents classically with seizures, intellectual disability, hypotonia , hepatomegaly, kidney disease, cataracts , hearing loss , and craniofacial abnormalities . Results of
laboratory studies will show increased VLCFAs , hepatic transaminases, and direct bilirubin.
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45. A 54-year- old woman comes to the physician because of a 10-day history of episodes of severe stabbing pain of her left cheek and jaw. She says that the pain occurs suddenly and can be precipitated by chewing : speaking , or brushing her teeth; it lasts
several seconds and occurs 20 to 30 times daily. She adds , It feels like lightning is striking my cheek . ' Touching the left cheek reproduces her symptoms. Which of the following is the most likely cause of this patient ' s symptoms ?
1
A ) Compression of the trigeminal nerve by an acoustic neuroma (vestibular schwannoma)

B ) Inflammation of the temporomandibular joint
C ) Inflammation of the trigeminal nerve by a multiple sclerosis plaque
D ) Microvascular compression of the trigeminal nerve
E ) Recurrent transient ischemia in the vertebrobasilar system
Trigeminal neuralgia is a neuropathic pain disorder that presents with severe shooting or burning pain within the innervated regions of the sensory branches of cranial nerve V (the trigeminal nerve). Cranial nerve V divides into three sensory branches , Vt to
which innervate the forehead (Vr) r the skin overlying the zygomatic and maxillary bone (V , and the skin overlying the mandible (V 3) . The pathophysiology of the pain is believed to be related to compression of the trigeminal nerve by adjacent blood vessels or bone
^
as it exits the skull base . Symptoms may be triggered by light touch , shaving swallowing , or may occur without any precipitant . The pain is generally described as severe. Treatment includes carbamazepine or surgical decompression .
,
Incorrect Answers : A . Br C . and E.
Compression of the trigeminal nerve by an acoustic neuroma (vestibular schwannoma ) ( Choice A ) would be unlikely, as acoustic neuromas generally occur in association with cranial nerve VIII and generally cause sensorineural deafness , vertigo and
,
disequilibrium . Pain would be an unusual presentation, as would a lesion large enough to also affect cranial nerve V.
Inflammation of the temporomandibular joint ( Choice B) would cause pain with chewing and be specifically located in the area of the temporomandibular joint . Patients tnay also complain of locking of the jaw.
Inflammation of the trigeminal nerve by a multiple sclerosis plaque ( Choice C ) is a known cause of trigeminal neuralgia however this patient demonstrates no symptoms of multiple sclerosis such as neurologic dysfunction affecting multiple body systems over time
,
(eg , urinary incontinence , weakness , or optic neuntis ) .
Recurrent transient ischemia in the vertebrobasilar system ( Choice E ) presents with functional loss affecting the brainstem and cerebellum , such as vertigo , ataxia , nystagmus nausea , or vomiting . Pain is not characteristic .
,
Educational Objective: Trigeminal neuralgia is a neuropathic pain disorder that presents with severe shooting or burning pain within the innervated regions of the sensory branches of cranial nerve V (the trigeminal nerve) . The pathophysiology of the pain is believed
to be related to compression of the trigeminal nerve by adjacent blood vessels or bone as it exits the skull base.
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46. A 2 -month-old girl is brought to the physician for a follow-up examination 2 days after a complete blood count was found to be abnormal . Her blood group is A . Rh-positive . She was born at term to a healthy 23 -year- old woman whose blood group is 0 . Rh -
positive . Birth weight was 3890 g ( 8 lb 9 oz) . Pregnancy and delivery were uncomplicated . The patient has been active and feeding well. Her temperature is 37.6°G (99.7DF ) , pulse is 120/min, and respirations are 30/ min. Physical examination shows no
abnormalities. Laboratory studies done since birth are shown .
Patient Age
24 Hours 1 Week 1 Month
Hemoglobin (g/dL) ( N=11— 15 ) 16.9 15.7 12.7
Hematocrit ( %) (N= 28- 45 ) 51 49 39
Leukocyte count (/mm 3) (N =5000-19, 500) 17.200 15.600 12.900
Segmented neutrophils 4% 3% 5%
Eosinophils 4% 4% 2%
Basophils 4% 2% 1%
Lymphocytes 69% 73% 77 %
Monocytes 19% 18% 15 %
Platelet count (/mm3) (N=150.000- 400, 000) 185.000 198,000 205,000
Which of the following is the most likely diagnosis ?
A } Alloimmune hemolytic disease of the newborn

B ) Congenital cytomegalovi rus in fe ct i on
C ) Congenital neutropenia
D ) DiGeorge syndrome
E ) Severe combined immunodeficiency
Congenital neutropenia refers to the presence of neutropenia at or around the time of birth and is the most likely diagnosis in this case . Neutropenia is defined by an absolute neutrophil count ( ANC ) of less than 1500/mm 3 although most patients with congenita!
neutropenia have an ANC less than 1000/mm 3, at which point the risk for bacterial infection increases. The underlying cause most commonly includes mutations that affect the production of myeloid cells . Bone marrow biopsy, if performed , may show decreased
cellularity with cells that are arrested at the promyelocyte or myelocyte stage. Many patients will remain largely asymptomatic . In more severe cases with lower neutrophil counts , patients may develop stomatitis and recurrent mucocutaneous ulcerations , often
with abdominal pain from gastrointestinal ulceration . Neutropenia is found in many conditions present at birth including Chediak-Higashi syndrome , X- linked agammaglobulinemia , and von Gierke disease , and should be distinguished from these by mutational
analysis and evaluation for concomitant physical findings .
Incorrect Answers : A . B : D , and E.
Alloimmune hemolytic disease of the newborn ( Choice A ) occurs in patients who are Rh-positive and are born to mothers who are Rh-negative but were previously sensitized either by a prior birth or blood transfusion to make anti-Rh antibodies. Both the patient
and her mother are Rh-positive , making this diagnosis unlikely.
Congenital cytomegalovirus infection ( Choice B ) causes hearing loss , seizures , a petechial rash , and intracranial calcifications in the neonate when acquired in utero. Hepatomegaly, splenomegaly, and lymphadenopathy are also commonly seen . The virus is
transmitted via the placenta from the mother , who often contracts the virus after interacting closely with young children .
DiGeorge syndrome ( Choice D) is caused by a 22q11 deletion that leads to failure of the third and fourth branchial pouches to develop . These structures give rise to the thymus and parathyroid gfands , and their absence leads to thymic aplasia and hypocalcemia
in the setting of cardiac and craniofacial defects . Patients are susceptible to viral and fungal infections. The definitive diagnosis requires fluorescence irr-situ hybridization to detect the missing DNA segment. Treatment is supportive.
Severe combined immunodeficiency ( Choice E) can result from numerous mutations but commonly presents with recurrent bacterial, viral and fungai infections caused by severe impairment in both B - and f - lymphocyte function .
Educational Objective : Congenital neutropenia is defined as neutropenia that is present at or around the time of birth, is not related to a secondary cause , and persists . In cases of mild neutropenia , symptoms are less common , although patients may eventually
develop stomatitis and gastrointestinal ulceration . In severe cases , there is a substantially heightened risk for invasive bacterial infection .
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47 . A 4 G -year- old woman comes to the physician because of a 2 -year history of progressive shortness of breath while supine; she now requires two pillows to help her sleep . She also has had a cough with occasional
production of rusty-colored sputum during this period. Her respirations are 16,'min . Bilateral crackles and a grade 4/6 mid -diastolic murmur are heard. Echocardiography shows left atrial dilation with mitral stenosis .
No other valvular lesions are noted . The photograph shown is characteristic of her disease process. Which of the following is the most likely cause of these findings ?
A ) Congenital rubella
B } Coronary artery atherosclerosis
C ) Illicit intravenous drug use
D ) Recurrent group A streptococcal infections
E ) Systemic sclerosis (scleroderma) with CREST syndrome
Rheumatic heart disease ; s a complication of acute rheumatic fever caused by group A streptococcal infection resulting in progressive inflammatory damage to the heart valves with fibrosis and calcification . It commonly causes insufficiency in the acute phase and
stenosis later in life , predominantly affecting the mitral valve . Rheumatic fever typically presents with joint inflammation pancarditis subcutaneous inflammatory nodules , erythema marginatum , and Sydenham chorea . Mitral stenosis presents with a diastolic
, ,
murmur radiating to the axilla . If severe enough, It can result in left atrial enlargement , cardiogenic pulmonary edema , and arrhythmias such as atrial fibrillation and flutter.
Incorrect Answers : A, B , C . and E.
Congenita! rubella ( Choice A) syndrome is caused by fetal rubella infection during pregnancy, which results in severe malformations in the fetus . It is diagnosed in the neonatal period and classically presents with bilateral hearing loss , congenital heart defects , a
violaceous rash , and hepatosplenomegaly .
Coronary artery atherosclerosis (Choice B) may result in chronic ischemic changes to the myocardium and risk for papillary muscle rupture in the setting of acute tissue infarction . It does not cause chronic inflammation and calcification of the mitral valve .
Illicit intravenous drug use ( Choice C ) is a risk factor for infective endocarditis caused by the introduction of microbes into the venous circulation . The tricuspid valve is most commonly affected . Vegetations may form on the valve , and patients may present with
fever, dyspnea , tricuspid regurgitation , and septic pulmonary emboli.
Systemic sclerosis (scleroderma ) with CREST syndrome ( Choice E ) is a subtype of scleroderma characterized by fibrotic skin changes of the distal extremities and face ; it is associated with calcinosis cutis, Raynaud phenomenon, esophageal dysmotility,
sclerodactyly, and telangiectasias.
Educational Objective: Calcification of the mitral valve can result in mitral stenosis , classically heard as an opening snap , followed by a diastolic rumble loudest over the cardiac apex . Mitral stenosis commonly occurs as a : ong-term complication of rheumatic hear!
disease caused by group A streptococcal infections .
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48 . A 25 -year- old man who immigrated to the USA from Pakistan 2 months ago comes to the physician for a follow-up examination. He was diagnosed with hepatitis C at the age of 5 years but has had no symptoms or clinical signs of this condition. Physical
examination shows no abnormalities . Serum studies done today show an AST activity of 68 U/L, ALT activity of 100 U/ L: and hepatitis C virus RNA of 1.5 million|U/mL A photomicrograph of the liver biopsy specimen is shown. Which of the following
characteristic features of virus-induced histopathology is seen in this patient ?
A ) Apoptosis
B ) Coagulation necrosis
C ) Endoplasmic reticulum proliferation
D ) lmmune-mediated cell lysis
E ) Mallory hyaline inclusion
Apoptosis is demonstrated in the photomicrograph provided, which shows a counc ; man body { eosinophilic cytoplasm) in the lower left quadrant of the slide. Councilman bodies represent hepatocytes in a state of apoptosis or necrosis , and their distinct
appearance histologically contrasts them against normal surrounding cetls and architecture . They possess a small nuclear fragment but no distinct nucleus and an intensely eosinophilic cytoplasm . They can be identified both in acute and chronic viral hepatitis ,
although in chronic hepatitis they may be associated with features of chronic injury, including spotty necrosis muftinucleated hepatocytes , and Kupffer cell hyperplasia. More severe forms of hepatic injury, including bridging and confluent necrosis , are less
,
common in chronic hepatitis C.
ncomeet Answers: B . C . D. and E.
Coagulation necrosis ( Choice B) , in contrast to apoptosis , is cell death that occurs as a result of ischemic injury and involves distinctly different cellular pathways . It is histologically characterized by absent nuclei but preserved ceil architecture that may persist for
several days, followed by cellular destruction via heterolysis.
Endoplasmic reticulum (ER) proliferation (Choice C ) may occur in cellular ischemia because of cessation of the ATP dependent sodium-potassium transporter in the plasma membrane ; increased quantity of ER may also occur in states of high protein synthesis
(eg , in plasma cells) , and in cases of considerable or repeated exposure to toxic substances degraded by the smooth ER (eg , in hepatocytes ). This i$ not seen on this photomicrograph .
lmmune -mediated cel! lysis ( Choice D) describes several distinct processes but commonly involves the binding of an antibody to the surface of cells , leading either to complement fixation with activation of the classical complement cascade or destruction by
,
cytotoxic T or natural kil er cells.
Mallory hyaline inclusions ( Choice E) are eosinophi ' c , spiral structures made of cytokeratin that are found in ballooning hepatocytes . They are seen frequently in aicoholic hepatitis and cirrhosis. They are not apparent on this slide .
Educational Objective: Councilman bodies are eosinophilic hepatocytes with a nuclear fragment that represent cells undergoing apoptosis They are frequently seen in both acute and chronic hepatitis .
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49. A GQ-year- old man is being evaluated for episodes of carpopedal spasm. Laboratory studies of serum show:
Ca 2+ 6.2 mg/dL
Albumin 4.0 g/dL
Phosphorus 8.6 mg/dL
Parathyroid hormone 200 pg/ mL ( N =10-65 pg/mL )
Which of the following conditions would most likely account for these findings?
A ) Acute tubular necrosis

B ) Chronic renal failure
C ) Dehydration
D } Rapidly progressive glomerulonephritis
E ) Renal cell carcinoma
Chronic renal failure can have variable cause such as with chronic prerenal disease in the setting of heart failure or cirrhosis with decreased renal perfusion , intrinsic renal disease such as nephrosclerosis or atherosclerotic renal artery disease , chronic nephritic or
;
nephrotic glomerular disease , or chronic postrenal obstructive disease . Chronic kidney disease is more common in older patients after years of underlying kidney injury. Active vitamin D (1 25- dihydroxycholecalciferol) is synthesized through cutaneous hepatic , and
, ,
renal routes , with the final conversion of 25 -hydroxycholecafciferol to active 1.25- dihydroxycholecalciferol in the kidney via 1-alpha hydroxylase . Patients with chronic kidney disease have diminished capacity for native vitamin D synthesis because of underlying
renal parenchymal damage . The decreased production of active vitamin D results in impaired gastrointestinal uptake of dietary calcium , leading to hypocalcemia . This in turn , leads to increased serum PTH and secondary hyperparathyroidism . Chronic renal failure
,
is also characterized by the inability of the kidney to excrete phosphate , resulting in hyperphosphatemia . Hyperphosphatemia and hypocalcemia result in the upregulation of PTH . which increases bony turnover in an attempt to raise serum calcium.
Incorrect Answers : A . C D, and E .

;
Acute tubular necrosis (Choice A) typically occurs following an ischemic or nephrotoxic insult to the kidneys which results in necrosis of the tubular epithelium . Granular muddy brown casts are common on urinalysis . It would not cause hypocalcemia .
,
Dehydration (Choice C } can result in prerenal acute kidney injury but would not lead to the hypocalcemia and secondary hyperparathyroidism seen in chronic renal failure .
Rapidly progressive glomerulonephritis ( Choice D ) is a nephritic syndrome characterized by acute renal failure associated with hematuria , red blood cell casts and hypertension . It does not cause hypocalcemia directly.
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Renal cell carcinoma (RCC ) (Choice E) is an adenocarcinoma of tubular epithelial cells. RCC is a common primary malignancy of the kidney and generally occurs in older , male smokers . It can present with gross or microscopic hematuria flank pain , weight loss , or
,
fever. Hypercalcemia can result from bony metastasis .
Educational Objective: Secondary hyperparathyroidism typically presents with increased PTH . hypocalcemia and hyperphosphatemia . It results from chronic renal failure because of the inability of the kidney to excrete phosphate and to produce active vitamin D .
,
which results in hypocalcemia . Hyperphosphatemia and hypocalcemia result in the upregulation of PTH , which increases bony turnover in an attempt to raise serum calcium.
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50 . A 1 6 -month -old girf is brought to the physician because she has refused to move her right arm since her older brother grabbed her right hand 1 hour ago to stop her from running into the street . On examination, she is holding the right arm in pronation . Any
motion of the right elbow produces pain. There is no visible edema . Which of the following is the most likely explanation for these findings ?
A ) Dislocation of the shoulder

B ) Fracture of the distal radius and ulna
C ) Salter - Harris type I fracture of the humerus
D ) Septic arthritis
E ) Subluxation of the radial head
Correct Answer : E
Dislocation or subluxation of the radial head is a common pediatric injury, known as a nursemaid elbow. It results from traction on the radial head: which displaces it from within its ligamentous annulus. This most often occurs in children of age 12- 36 months , and
often arises from defensive maneuvers by parents or caretakers when grabbing the child's arm to prevent running into traffic or similarly endangering oneself. It can also arise from routine play if a parent, older sibling , or caregiver is swinging the child by his or her
arms. Sometimes a pop may be heard or dunk may be felt, usually followed by immediate crying . Children are generally consolable following the injury , and they often present with the arm held in a neutral, extended pronated position as this is generally the
; ;
position of best comfort . They will generally grimace or cry with palpation of the radial head . Diagnosis is clinical and radiographs are seldom necessary ; even if performed , they may not show misalignment as this is a ligamentous injury and pediatric ossification of
,
:he elbow occurs between ages 2-12 years making the structures poorly visible on radiograph . Treatment involves reducing the radial head back into the annulus through physical manipu ation by hyper -pronation , supination-flexion maneuvers , or both . Seldom is
operative reduction necessary, nor is sedation to achieve appropriate reduction . A successful reduction is determined by the child reusing his or her arm. Recurrent injuries are common .
Incorrect Answers : A . B : C, and D.
Dislocation of the shoulder ( Choice A ) would be uncommon following a traction maneuver on the arm . Shoulder dislocation may result from abduction , extension , and rotation, or as a consequence of trauma or muscle spasm (such as in seizure or electrocution) .
Examination shows a flattened depression inferior to the acromion , and a palpable mass often anterior to the shoulder near the coracoid . The elbow is unaffected .
Fracture of the distal radius and ulna ( Choice B ) generally occurs following a fall on an outstretched limb and presents with pain in the distal forearm . The elbow is generally unaffected though complex fracture patterns may involve fractures of the distal radius , ulna ,
,
their articulation , and the proximal ulna or radius, such as in Monteggia or Galeazzi patterns .
Salter -Harris type ! fracture of the humerus (Choice C ) is generally radiographically occult and presents with a nondisplaced fracture through the affected physis . Patients present with pain in the area of the affected physis . and treatment includes immobilization . It
would be unlikely to occur with a low-energy traction mechanism .
Septic arthritis ( Choice D) is a common surgical emergency in the pediatric population. It presents with acute onset joint pain, erythema swelling , refusal to bear weight and signs and symptoms of sepsis. Treatment is with antibiotics and may require operative
, ,
irrigation and debridement .
Educational Objective : Dislocation or subluxation of the radial head is a common pediatric injury, known as a nursemaid elbow . It results from traction on the radial head , which displaces it from within its ligamentous annulus . Diagnosis is clinical , and generally,
bedside reduction without sedation or analgesia is feasible with patients typically demonstrating a prompt return of function.
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Exam Section 1: Item 1 of 50 National Board of Medical Examiners^

Comprehensive Basic Science Self-Assessment

A ) Abnormal neural crest development

Incorrect Answers : B, C , D: E , and F.

Incorrect Answers : A, C , D . and E.

Incorrect Answers : A . B C . and E.

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converting phenylalanine to tyrosine.

Incorrect Answers : A . B C . D, and E

Incorrect Answers : A . Cr D, and E.

Incorrect Answers : A . C , D, and E.

Incorrect Answers : A , C D . E F, and G .

Incorrect Answers : A . C , D , and E.

A ) Angular gyrus ( Gerstmann syndrome)

Incorrect Answer : A, B. C . and E.

Incorrect Answers : A, B . C . D , E . and G.

The anterior hypothalamic nucleus ( Choice A) is involved in thermoregulation , specifically in cooling.

The posterior hypothalamic nucleus ( Choice E ) is involved in thermoregulation specifically in heating .

Incorrect Answers : A, C , D , E, F, G, and H .

A ) Chloride conductance in the nerve terminal

Incorrect Answers : A, 6 , C, and D.

Incorrect Answers : A . B C . D, and E

Incorrect Answers : A, C , D , and E.

formation and Jead to apoptosis of infected cells .

Incorrect Answers : A . C D E : F: and G .

labeled end-systolic pressure points is most likely?

Incorrect Answers : A . B. C . and E.

Left ventricular end- diastolic

Incorrect Answers : A, B : D, and E.

Incorrect Answers : A . C , D , and E.

D ) Neutrophil-specific granule deficiency * * ** «£

E ) Wiskott- Aldrich syndrome * t*

Incorrect Answers : A , C D . and E.

Incorrect Answers : A . B , and D .

A ) Activation of the complement cascade

Incorrect Answers : A . 6 : D . and E.

prone to infections, especially viral infections.

A ) Decreased 21-hydroxylase activity

with endometrial lining .

Incorrect Answers : A . B : D , and E.

Muscle Glucose Adipose Hepatic

Incorrect Answers : A, B. C, E. and F.

Incorrect Answers : A, 0. C, and D.

Incorrect Answers : A, B. D, and E.

deformities , and fibrosis of the renal parenchyma .

Incorrect Answers : A, B. C . and E.

axial masses that compress the adjacent brain parenchyma .

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A ) Decreased glomerular filtration coefficient

Incorrect Answers : A . B . Ca D, and F.

A ) Acute myelogenous leukemia

symptom-triggered appointments) and possible psychotherapy.

incorrect Answers : A . C , D , and E.

punctate marks on the abdomen and legs .

morphogenesis from an inadequate intrauterine environment.

Incorrect Answers : B, C : D: and E.

Incorrect Answers : A , Bp D . and E.

Incorrect Answers : A . B. C . D , E . F. and G .

characteristic . Large volume hematemesis is not a feature of CMV esophagitis .