Form 25 Flashcards
- A 9-year-old boy has had alopecia and hypocalcemia since birth. His serum 1;25-dihydroxycholecalciferol concentration is within the reference range: serum 24;25-dihydroxycholecalciferol is undetectable. Serum parathyroid hormone concentration is above
the upper limit of the laboratory assay and needs to be reassayed at a dilution. The results are pending. Which of the following is the most likely cause of his condition?
A) Loss-of-function mutation in the calcium-sensing receptor
B) Multiple endocrine neoplasia type I
C) Mutations inactivating the vitamin D 24-hydroxylase gene
D ) Mutations inactivating the vitamin D receptor
Correct Answer: D.
Vitamin D plays a role in serum calcium and phosphate homeostasis by promoting the intestinal absorption of calcium and phosphate. Parathyroid hormone (PTH) also has a role in calcium and phosphate regulation by stimulating osteoclastic bone reabsorption
and distal convoluted tubular calcium reabsorption and phosphate excretion in the kidney Vitamin D deficiency can be caused by malabsorption in the intestinal tract, malnutrition or insufficient dietary intake, and decreased sun exposure. Decreased concentration
of vitamin D results in decreased intestinal cacium absorption and hypocalcemia, sensed by the parathyroid gland via calcium-sensing receptors, which leads to an increase in secretion of PTH to normalize serum calcium concentration. Increased PTH causes
bone resorption, liberating calcium and phosphorus, otherwise stored in bone. In this patient, 1,25-dihydroxycholecalciferol, the active form of vitamin D, is within reference range. However the vitamin D receptor must also exist and function appropriately for the
hormone to exert its effect. Vitamin ID binds a nuclear receptor, exerting its effect by gene transcription. In this case, a normal concentration of Vitamin D with persistent hypocalcemia suggests an inactivating mutation in the receptor itself, or a mutation in a
regulatory sequence that prevents transcription of the genes coding for the receptor. In turn, the patient experiences persistent hypocalcemia despite normal vitamin D concentration, as the receptor mutation prevents the action of vitamin D in promoting the
intestinal absorption of ca cium.
Incorrect Answers: A. B, and C.
Loss-of-function mutation in the calcium-sensing receptor (Choice A) in the parathyroid gland would prevent the parathyroid gland from sensing low concentrations of calcium and reacting by secreting PTH. This would cause hypoparathyroidism, not
hyperparathyroidism as seen in the patient.
Multiple endocrine neoplasia type I (Choice B) is characterized by often functional pituitary, pancreatic, and parathyroid tumors. Pituitary tumors may secrete prolactin or growth hormone, pancreatic tumors may secrete insulin, glucagon, or vasoactive intestinal
peptide, and parathyroid adenomas may secrete PTH. A functionally active parathyroid adenoma would cause an increase in PTH. and because of the role of PTH in calcium reabsorption and bone resorption, hypercalcemia would result.
Mutations inactivating the vitamin D 24-hydroxylase gene (Choice C) would result in decreased concentration of 24,25-dihydroxycholecalciferol, an inactive metabolite. Vitamin D would persist in its active form as a result, which may indirectly result in
hypercalcemia.
**Educational Objective: **Vitamin D plays a role in serum calcium and phosphate homeostasis by promoting the intestinal absorption of calcium and phosphate. Vitamin D deficiency typically leads to decreased intestinal calcium absorption, hypocalcemia, increased
PTH secretion, and increased PTH-mediated bone resorption.
Assuming the positive predictive value of a test is 50% and the negative predictive value is 75%; which of the following tables are consistent with these values?
Correct Answer: A.
Educational Objective: Positive predictive value defines the proportion of positive test results that are true positive and is calculated as TP / (TP + FP) Negative predictive value defines the proportion of negative test results that are true negative and is calculated as TN / (TN + FN).
A 43-year-old woman comes to the physician because of vague discomfort, nausea, easy bruising; and weight loss. Her prothrombin time is increased. The most likely cause of the increased prothrombin time is damage to which of the following cells?
A ) Endothelial cells
B) Fibroblasts
C) Hepatocytes
D ) Macrophages
E) Skeletal muscle cells
F ) T lymphocytes
Correct Answer: C.
C and S), complement, apoproteins, triglycerides, cholesterol, bile acids, and albumin, and play critical roles in biochemical metabolism (eg, gluconeogenesis). Many manifestations of liver disease can be attributed to dysfunction of hepatocytes, which are the
primary parenchymal cells within the liver. Prolonged prothrombin time (PT) is a common finding as a result of deficiency of factor VII, and in this case, the patient’s easy bruising reflects this acquired coagulopathy. Hypoglycemia from impaired gluconeogenesis. nausea from increased gut transit time, jaundice from hyperbilirubinemia, and hypogonadism from altered metabolism of estrogens are all common findings in patients with chronic liver dysfunction. Malnutrition and weight loss also frequently occur.
Incorrect Answers: A. B D, E, and F.
Endothelial cell damage (Choice A) results iin hypercoagulability and associated vascular disease. Endothelial cells line the inner lumen of blood vessels and function to reduce clotting. Damage to endothelial cells, which occurs via multiple mechanisms (eg.
hypertension, smoking, hyperlipidemia, hyperglycemia), results in local nitric oxide deficiency, fibrosis, inflammation, and calcification, and can lead to myocard al infarction, stroke, and peripheral vascular disease.
Fibroblast damage (Choice B) would result in disordered synthesis of the extracellular matrix. As fibroblasts are ubiquitous and exist in nearly every organ system, local deficiencies would produce variable phenotypic effects. Damage to fibroblasts iin the skin, for
example, impairs the synthesis and release of collagen thereby altering the normal process of wound healing.
Macrophage damage (Choice D) and dysfunction predisposes to infection. Disorders in the activation and/or chemotaxis of macrophages ead to an increased susceptibility to mycobacterial infections as a result of failed intracellular killing and granuloma formation.
Skeletal muscle cell damage (Choice E) is a common finding in acquired and inherited conditions such as muscular dystrophy, mitochondrial myopathy, toxic, metabolic, and inflammatory myopathies, and rhabdomyolysis. Symptoms are determined by the
mechanism of injury but result in either pain, weakness, or both affected muscles.
T lymphocyte damage (Choice F), dysfunction, or absence is typical of immunodeficiency syndromes and can be genetic or acquired. HIV/AIDS affects CD4+ T lymphocytes specifically resulting in susceptibility to a wide array of opportunistic pathogens (eg, fungal,
mycobacterial, viral, and bacterial). Iatrogenic damage to T lymphocytes such as that which occurs with cytotoxic chemotherapy also predisposes to systemic infection.
Educational Objective: Hepatocytes are critical for the synthesis of multiple coagulation factors. Dysfunction of hepatocytes results in an increased PT/INR secondary to the impaired synthesis of factor VII and may result in a predisposition to bleeding.
A 63-year-old man has had this gradually enlarging lesion on his right forearm for the past 3 years. Which of the following is the most likely diagnosis?
A ) Actinic keratosis
B} Blue nevus
C) Compound nevus
D ) Dermatofibroma
E) Halo nevus
F ) Hemangioma
G) Malignant melanoma
H ) Pyogenic granuloma
I ) Seborrheic keratosis
J) Squiamous cell carcinoma
Correct Answer: G.
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. Malignant melanoma can 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.
Educational Objective: Melanoma should be suspected when lesions demonstrate asymmetry, border irregularity, variable coloration, diameter greater than 6mm, or changing features.
A 60-year-old man has a surgical excision of a brain mass; a photomicrograph of excised tissue is shown He has smoked 1 pack of cigarettes daily for the past 50 years. His blood pressure is 130/90 mm Hg.
Laboratory studies show polycythemia, hypercalcemia, and microscopic hematuria. Immunostaining of the tissue is positive for epithelial membrane antigen and negative for carcinoembryonic antigen. Which of the
following is the most likely site of the primary neoplasm?
A) Colon
B) Kidney
C) Liver
D) Lung
E) Lymph node
F) Prostate
G) Testis
Correct Answer: B.
Renal cell carcinoma (RCC) is an adenocarcinoma of tubular epithelial cells. RCC is the most common primary malignancy of the kidney and most commonly occurs in older male smokers. It can present with gross or microscopic hematuria, flank pain: weight
oss: or fever. Laboratory analysis may show polycythemia or hypercalcemia as a result of associated paraneoplastic syndrome production of erythropoietin or parathyroid hormone-related peptide. Hypercalcemia can also result from bony metastasis. Diagnosis of
RCC typically occurs with contrast-enhanced CT scan or MRI and is confirmed by biopsy at the time of nephrectomy. Biopsy of RCC is uniquely characterized by polygonal clear cells: because of the accumulation of lipid and carbohydrate content in the cells. It spreads hematogenously and commonly presents as a metastatic neoplasm. The brain and lung are frequent sites of metastasis.
Educational Objective: Renal cell carcinoma often presents in older men with a history of cigarette smoking, and the brain is a potential site of metastasis. Laboratory analysis may show hematuria along with hypercalcemia or polycythemia secondary to paraneoplastic syndromes. Histology typically demonstrates polygonal clear cells related to the accumulation of lipid and carbohydrate content in the cells.
- The biological effects of thyroid hormone and retinoic acid are mediated through similar mechanisms. Which of the following properties is common to the receptors for these two compounds?
A) Ability to activate phospholipase C
B) DNA-binding domain
C) Formation of a dimer on binding of hormone
D) Interaction with a G protein
E) Tyrosine kinase activity
Correct Answer: B.
Educational Objective: Nuclear hormone receptors contain DNA-binding domains and exert their effects by serving as DNA transcription factors. Common examp es of nuclear receptors include the thyroid hormone receptor and the retinoic acid receptor
- A 57-year-old man conies to the physician because of an intermittent cough and a 9-kg (20-lb) weight loss over the past 6 months. He has smoked 1 pack of cigarettes daily for 42 years. His serum calcium concentration is 13.3 mg/dl_. An x-ray of the chest
shows a 4-cm central mass in the left lung. Which of the following is the most likely diagnosis?
A) Adenocarcinoma of the lung
B) Large cell lymphoma
C) Metastatic osteosarcoma
D ) Metastatic renal cell carcinoma
E) Small cell carcinoma of the lung
F ) Squamous cell carcinoma of the lung
Correct Answer: F.
Squamous cell carcinoma of the lung is the second most common type of primary lung cancer after adenocarcinoma. Risk factors for all major types of lung cancer include tobacco use, secondhand smoke. asbestos: or 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 because of paraneoplastic parathyroid hormone-related peptide (PTHrP) production. Histologic characteristics include
polygonal cells with intercellular bridges, eosinophilic cytoplasm, keratin pearls, and extensive necrosis. Luing cancer in general typically presents with cough, unintentional weight loss, hemoptysis, chest pain, dyspnea, and hoarseness; occasionally, wheezing, focal rhonchi or hypedrophic osteoarthropathy may be noted on examination. 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. It is often detected once metastatic, at which point the prognosis is poor.
Educational Objective: Centrally located primary lung cancers include squamous cell carcinoma of the lung and small cell carcinoma of the lung. Squamous cell carcinoma is the more common subtype and is associated with hypercalcemia because of
paraneoplastic PTIHrP production.
A 34-year-old woman is brought to the emergency department by her husband because of ain inability to see objects in the peripheral visual fields in both eyes for 1 day. Her temperature is 37.2aC (99°F), pulse is G8/min. respirations are 16/min, and blood
pressure is 124,78 mm Hg. Automated computerized perimetry examination shows a loss of the temporal visual field in both eyes. Neurologic examination shows no other abnormalities. This patient is most likely to have which of the following additional
findings?
A ) Amenorrhea
B) Aphasia
C) Double vision
D) Loss of memory
E) Seizures
Correct Answer: A.
This patient’s bitemporal hemianopsia is most likely the result of optic chiasm compression from a pituitary adenoma: which is often associated with amenorrhea in women secondary to the overproduction of prolactin. The pituitary gland is in the sella turcica. A
pituitary adenoma is a benign brain tumor that can present with mass effect symptoms such as headache and bitemporal hemianops a (loss of bilateral temporal visual fields). Bitemporal hemianopsia occurs because of compression of the optic chiasmi which
contains fibers from the bilateral nasal retina (containing visual information from the temporal eye fields) . Pituitary adenomas can cause symptoms from hyperpituitarism or hypopituitarism, depending on whether the tumor is functionally secreting hormones.. The
most common functional pituitary adenoma is a prolactinoma: other types of pituitary adenomas secrete follicle-stimulating hormone (FSH); luteinizing hormone (LH). adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), or growth hormone
(GH). Prolactinomas suppress gonadotropin-releasing hormone (GnRH). which results in decreased FSH and LH production and manifests as amenorrhea. Additionally if a pituitary adenoma is nonfunctional but sufficiently large: it can interfere with normal hormone secretion by the pituitary gland: causing hypopituitarism. In this setting, decreased secretion of FSH and LH could also manifest as amenorrhea.
**Educational Objective: **Pituitary adenomas can cause mass effect symptoms such as headache and bitemporal hemianopsia from compression of the adjacent optic chiasm Additionally, they may be functional or nonfunctional in nature. Hypersecretion of hormones: most commonly prolactin, can manifest with amenorrhea and galactorrhea in females.
- A 22-year-old woman is admitted to the hospital because of a 10-day history of polydipsia and polyuria. She says that the urge to urinate often awakens her at night. She has been taking lithium carbonate for 2 years for bipolar disorder: her dosage was
increased 6 months ago because of recurrent severe manic episodes. Her vital signs are within normal limits. Physical examination shows no abnormalities. Over the next 24 hours: urine excretion totals 6.5 L. Laboratory studies at this time show a serum
sodium concentration of 148 mEq/IL. serum osmolality of 315 mOsmol/kg, and urine osmolality of 75 mOsmol/kg. After administration of desmopressin, urine output and osmolality do not change. Which of the following mechanisms is the most likely cause of the polyuria in this patient?
A) Decreased secretion of ADH (vasopressin)
B) Inhibition of cAMP-mediated processes iin the collecting duct
C) Osmotic diuresis due to increased amounts of glucose in the tubule
D ) Polydipsia-induced washout of the renal interstitial concentration gradient
E) Renal medullary necrosis due to decreased papillary blood flow
Correct Answer: B.
Nephrogenic diabetes insipidus (NDI) is commonly acquired secondary to medications or electrolyte disturbances. The pathophysiology of NDI occurs such that the renal collecting duct becomes insensitive to antidiuretic hormone (ADH) produced by the posterior pituitary. Normally. ADH triggers the insertion of aquaporin channels into the collecting duct membrane via a cAMP-mediated pathway. By consequence, when there is inhibition of this process in the collecting duct, as in NDI, the ability of the kidney to recaim free water is compromised. Dehydration results, as is demonstrated by this patient, along with symptoms of polydipsia (compensatory response to low serum volume or increased serum osmolarity) and polyuria or incontinence as a result of the large volume of dilute urine produced). NDI is an adverse effect of chronic lithium use. Lithium concentrates within the cells of the renal collecting duct and interferes with the signaling pathway related to ADH, leading to limited aquaporin insertion and resultant NDI. In severe cases of dehydration, vital signs may disclose tachycardia and hypotension. Physical examination discloses no abnormalities, apart from potential signs of volume depletion (eg, weak pulse, skin tenting). Laboratory studies show increased serum osmolarity, hypernatremia, and inappropriately dilute urine. Normally, urine should be concentrated in states of hyperosmolar serum, as the main physiologic function of ADH is to reclaim water, thereby maintaining serum osmolarity and sodium balance in addition to plasma volume. Desmopressin, an ADH analog, is used as a means of differentiating nephrogenic from central Dl. Central Dl occurs because of an absence of ADH production, not a failure of the renal collecting tubule to respond to it. If urine output and serum osmolarity decrease following desmopressin administration, a central cause of Dl (eg, head trauma, hypothalamic damage, pituitary tumor) should be investigated. No change in response to desmopressin indicates that the cause of Dl is nephrogenic. The treatment of NDI includes volume repletion plus thiazide diuretics.
**Educational Objective: **Nephrogenic diabetes insipidus is an adverse effect of lithium carbonate. Lithium impairs the ability of the collecting tubule to reclaim free water by interfering with the pathway of antidiuretic hormone in the cells. Patients typically present with polydipsia, polyuria, hyperosmolar serum, dilute urine, and failure to respond to desmopressin.
- A 77-year-old woman dies in the hospital after a long illness. Her vertebral column, obtained at autopsy is shown in the photograph. The process shown is most likely associated with an increase in which of the
following?
A) Calcium
B) Estrogen
C) lnterleukin-1 (IL-1)
D) Monoclonal immunoglobulin
E) Vitamin D
Correct Answer: C.
Osteoporosis is a common condition that is characterized by the progressive loss of bone mineral density leading to decreased bone strength. This decreased bone mineral density often leads to fragility fractures, which can greatly decrease mobility and increase the risk of death in elderly individuals. The disease classically affects postmenopausal women with inflammatory disorders, and individuals with metabolic or endocrine disorders such as hypercortisolism or hyperparathyroidism. Osteoporosis can also be induced
by long-term treatment with medications that cause an increase in bone resorption such as corticosteroids. The diagnosis is made using a DEXA scan via calculation of a T-Score. A T-score of -2.5 or less, that is a bone density measurement that is less than 2.5 standard deviations below the mean, is diagnostic of osteoporosis. T-scores between -1.0 and -2.5 are defined as osteopenia, lnterleukin-1 (IL-1) is also known as osteoclast activating factor. IL-1 leads to an increase in RANK ligand signaling and subsequent osteoclast-mediated bone resorption. Osteoporosis is thereby characterized by an increase in osteoclast number and activity, which is driven by IL-1.
**Educational Objective: **The balance of osteoblast and osteoclast interactions is key in the maintenance of bone mineral density, lnterleukin-1, also called osteoclast activating factor, can result in bone mineral density loss when increased.
- A IQ-year-old boy is brought to the physician because of a 3-day history of difficulty walking because his right foot drops when he lifts it. He is a member of a wrestling team at his high school. Physical examination shows weakness of the right ankle dorsiflexor muscles. The right ankle evertor muscles have full power. Sensation to pinprick is decreased between the great and second toes of the right foot. Sensation over the rest of the foot is normal. Which of the following nerves is most likely damaged in this patient?
A ) Common fibular (peroneal)
B) Deep fibular (peroneal)
C) Sciatic
D ) Superficial fibular (peroneal)
E) Tibial
Correct Answer: B.
Educational Objective: The peripheral nerves of the leg are often sites of compression injury or entrapment causing sensory loss and motor weakness. The superficial fibular nerve everts the foot, while the deep fibular nerve dorsiflexes the foot, and the tibial nerve plantarflexes the foot. Weakness in these movements can indicate which nerve is injured.
- During a study on exercise: a 45-year-old woman ruins on a treadmill for 30 minutes. An increase in which of the following is most likely to change gastrocnemius muscle blood flow in this woman?
A) Interstitial adenosine concentration
B) Interstitial amino acid concentration
C) Interstitial gIucose concentration
D ) Interstitial oxygen tension
E) Parasympathetic stimulation
F ) Sympathetic stimulation
Correct Answer: A.
During aerobic exercise, the cellular consumption of adenosine triphosphate (ATP) increases. Myosin motor proteins dephosphorylate ATP and subsequently use the energy released to generate muscle contraction. Adenosine will become diphosphate, monophosphate, or completely without phosphate as a result of this reaction, and it must then be reconverted to ATP via the Krebs cycle and oxidative phosphorylation in the mitochondrion. Byproducts of energy metabolism regulate regional blood flow, such as carbon dioxide and organic acids. Additional y: as the interstit al adenosine concentration increases, blood vessels dilate in response. This is known as exercise hyperem a. and it occurs through mediation from local regulators. Increased acidity, adenosine: hypoxia: nitric oxide: and prostaglandins are all important mediators of exercise-induced vasodilation. Adenosine is also a vasodilator in coronary vascular smooth muscle as well as in skeletal muscle. Adenosine modulates vasodilation by binding to the adenosine receptor and increasing cyclic adenosine monophosphate (cAMP) This leads to inhibition of myosin light chain kinase and vascular smooth muscle relaxation.
**Educational Objective: **There are multiple mediators of local muscle blood flow. These include adenosine, lactate, hydrogen ions, and the part al pressures of oxygen and carbon dioxide. These autoregulatory mediators serve to increase skeletal muscle blood flow during exercise.
- A 67-year-old man is brought to the physician because of a 2-day history of double vision and drooping of his left eyelid. He has no history of trauma to the eye. His vital signs are within normal limits. Physical examination shows ptosis of the left eyelid. When the eyelid is raised manually, the eye is fixed in the out position and the pupil is dilated. The visual acuity of the left eye is within normal limits. Which of the following is the most likely cause of these findings?
A) Aneurysm of the posterior communicating artery
B) Compression of the superior cervical ganglion
C) Damage to the trochlear nerve
D ) Occlusion of the scleral venous sinus
E) Tumor of the optic nerve
Correct Answer: A.
This patient’s presenting findings of unilateral ptosis; exotropia and hypotropia (inferior and lateral pupil position), and mydriasis (pupillary dilation) are consistent with an oculomotor nerve palsy. Two of the most common causes of acquired oculomotor nerve palsy are microvascular ischemia and nerve compression from an adjacent vascular aneurysm, commonly located at the posterior communicating artery (PCA). Upon leaving the brainstem, the oculomotor nerve courses beneath the posterior cerebral and posterior communicating arteries and is vulnerable to aneurysmal compression at this location. The fibers responsible for control of the pupil are found on the superficial aspect of the oculomotor nerve and are thus first affected by external compression. This distinguishes acquired oculomotor nerve palsy caused by aneurysmal external compression from palsy caused by microvascular ischemia, which typically spares the pupil. The detection of a new oculomotor nerve palsy is therefore a medical emergency, as aneurysmal rupture can lead to a life-threatening subarachnoid hemorrhage. A PCA aneurysm is diagnosed via CT angiography, MR angiography, or conventional angiography.
Educational Objective: Aneurysms of the posterior communicating artery may compress the ipsilateral oculomotor nerve, resulting in diplopia, mydriasis, exotropia, and hypotropia. They are diagnosed on CT angiography, MR angiography, or conventional angiography.
A 62-year-old man conies to the physician for a follow-up examination. Two weeks ago; he was discharged from the hospital after sustaining an acute myocardial infarction. He smokes 2 packs of cigarettes and drinks four 12-oz beers daily. His diet mostly consists of cured meats and fast food. He does not exercise. The patient tells the physician. “I know that I need to make some changes in how II live so that my heart can be healthier. I just don’t have the willpower to quit smoking and drinking and all that stuff right now.” Which of the following best describes this patient’s stage of behavioral change?
A ) Precontemplation
B) Contemplation
C) Preparation
D ) Action
E) Maintenance
Correct Answer: B.
In this scenario, the patient is aware of the potential consequences of his unhealthy habits and is considering reversing the habits. Although he has identified that his behavior is detrimental, he is indecisive about whether he is ready to act, which is consistent with the contemplation stage. The stages of behavioral change are used to define a patient’s readiness to change a health-related behavior such as substance use, diet, or exercise habits. In sequential order the stages of behavioral change are precontemplation, contemplation, preparation, action, maintenance,, and termination. Physicians aim to move patients through these stages overtime with an interview technique called motivational interviewing. Motivational interviewing involves using open-ended, non-judgmental questions to he p the patient explore their reasons for wanting to change or maintain the habit.
Educational Objective: The contemplation stage of behavioral change refers to ambivalence about changing a behavior, iin which the patient expresses knowledge of the consequences of their detrimental behavior but is not yet prepared to make plans to change. Motivational interviewing is a technique used by physicians to promote a patient’s readiness for change.
- A 35-year-old man conies to the physician because of a 2-year history of slowly progressive muscle weakness of hiis thighs. His father and paternal uncle have a disorder involving proximal muscle weakness of the lower extremities. Physical examination shows no other abnormalities. A muscle biopsy specimen shows ragged red fibers. Electron-microscopic examination of this specimen is most likely to show which of the following inclusions?
A) Intranuclear filamentous
B) Lysosomal
C) Mitochondrial crystalline
D) Paranuclear filamentous
E) Sarcoplasmic reticular
Correct Answer: C.
Mitochondrial crystalline inclusions on electron microscopy iin association with proximal muscle weakness, ragged red fibers on muscle biopsy: and a compatible family history are consistent with mitochondrial myopathy. Mitochondria are the cellular organelles that produce ATP via oxidative phosphorylation, a process that requires four enzyme complexes to produce a transmembrane potential that is ultimately used to produce ATP via ATP synthase. Mitochondrial DIMA is separate from somatic nuclear DNA; and mutations in genes encoding any of these complexes can result in the failure of oxidative phosphorylation, which results in a subsequent failure to generate ATP: and consequential myopathy and neurologic symptoms. However, there are additional mutations that affect mitochondrial RMA translation, trafficking and incorporation of respiratory protein complexes, and maintenance of the inner mitochondrial membrane that can also lead to mitochondrial myopathy. As both the skeletal muscle and neurologic system require vast quantities of ATP for normal function, these are the two organ systems most common y affected by mitochondrial DNA mutations. Musculoskeletal manifestations include muscle pain: fatigue, exercise intolerance, and increased concentrations of creatine kinase, while potential neurologic symptoms may include ophthalmoplegia, seizures, myoclonus, and peripheral neuropathy. Mitochondr al diseases are strictly inherited through the mother, as sperm do not contain mitochondria to contribute to the fertilized embryo. As a result of the failure of energy metabolism, the cells may compensate by producing additional mitochondria. On muscle biopsy, these mitochondrial aggregates, when visualized on the background of the myofibers, appear as ragged red fibers. Electron microscopy demonstrates abnormal mitochondrial crystalline inclusions
Educational Objective: Mitochondrial crystalline inclusions on electron microscopy and ragged red fibers on muscle biopsy in a patient with inherited proximal muscle weakness is characteristic of mitochondrial myopathy.
A 49-year-old woman comes to the emergency department because of a 3-day history of fever shortness of breath, and confusion. She is a postal worker. Her temperature is 38.4X (101 2°F): respirations are 28/min, and blood pressure is 100/60 mm Hg.
Physical examination shows nuchal rigidity. Breath sounds are decreased on the right side of the clhest. A lumbar puncture is done. Analysis of cerebrospinal fluid (CSF) shows:
Glucose 18 mg/dL
138 mg/dL
638/mm3
Total protein
Leukocyte count
Segmented neutrophils
Monocytes
87%
13%
RBC 2300/mm3
A Gram stain of CSF shows large, gram-positive; spore-forming bacilli . A chest x-ray shows marked widening of the mediastinum. Which of the following extracellular virulence factors most likely enables the causal organism to evade phagocytosis?
A) Alginate
B) Glucuronoxylomannan
C) Hyaluronic acid
D ) Polyglutamic acid
E) Pollyribitol phosphate
Correct Answer: D.
Anthrax is the disease caused by the bacterium Bacillus anthracis, which manifests with pulmonary. cutaneous: or gastrointestinal syndromes. The hallmarks of pulmonary anthrax include cough; shortness of breath, and chest pain within weeks to months after inhalation. Pulmonary anthrax is often fatal, which may occur via hemorrhagic mediastinitis. Anthrax also causes cutaneous lesions, often painless, necrotic eschars that are generally easily treated with antibiotics. Ingestion of anthrax-infected meat can cause diarrhea and abdominal pain. The pathogen is a gram-positive rod and facultative anaerobe, which arranges in chains on microscopy. The bacterium has two principal virulence factors, which are its polyglutamic acid capsule and toxin production. The polyglutamic acid capsule serves to prevent phagocytosis. Specific toxins produced by the bacterium include lethal factor (LF) and edema factor (EF). LF leads to apoptosis of macrophages, while EF alters cyclic adenosine monophosphate signaling pathways within the immune cells.
Educational Objective: Anthrax is a pathogenic bacterium, which uses a polyglutamic acid capsule to evade phagocytosis. Many other bacteria produce polysaccharide or glycosaminoglycan capsules that act in a similar fashion to protect the bacteria and increase virulence.
An investigator is designing a study to compare a new behavioral program for attention-deficit/hyperactivity disorder (ADHD) with the standard behavioral modification program for this disorder. Because ADHD is more common among boys: girls and boys are
randomized into the two treatment groups separately. Which of the following types of treatment allocation is most likely being used in this study?
A ) Alternation
B) Open
C) Outcome-adapted
D ) Simple random assignment
E } Stratification
Correct Answer: E.
Stratification describes the allocation of subjects or the analysis of results within a trial by a factor other than the treatment given. If involves subdividing a study population into homogeneous subgroups then analyzing each subgroup in comparison to the study population or other subgroups. Advantages of this technique are that it permits analysis of subpopulations that may vary from a population at large. In this case: the researchers speculate that since ADHD is more common among boys: there may be a meaningful difference when comparing the new and standard treatment programs applied to boys as applied to girls; whereas that meaningful difference may not be detected if the combined population is analyzed. Stratification is one method of reducing confounding variables. In this case, the study population has been stratified based on gender between the new and standard interventions.
Educational Objective: Stratification describes allocating subjects or results by a factor that is not necessarily the treatment administered; groups may be stratified or subdivided based on age, gender, profession, ethnicity, or other demographic features. It is one
method to control for confounding variables.
A 55-year-old woman is scheduled to undergo tnansvaginaI hysterectomy and oophorectomy for dysfunctional uterine bleeding. During the procedure: the uterus must be separated from all surrounding pelvic structures. Identification and incision of which of
the following structures that attaches to the cervical region and extends posteriorly is most appropriate in this patient?
A) Mesometrium
B) Mesosalpinx
C) Mesovaiiium
D ) Ovarian ligament
E) Round ligament of the uterus
F) Uterosacral ligament
orrect Answer: F.
The uterosacral ligament is one of the structures that supports the uterus and holds it in place in the pelvis. It is a paired structure that connects the uterus to the sacrum at the level of the cervix. They may also be called the rectouterine ligaments or sacrocervical
igaments. The uterus is also supported by the broad ligament which attaches to the superior aspect of the uterus and is a layer of peritoneum. The pubocervical ligaments and cardinal ligaments join the uterosacral ligament in supporting the middle portion of the uterus. The inferior portion of the uterus receives further support from the muscular components of the pelvic floor such as the levator ani. Each of these connections must be severed in order to successfully remove the uterus during a hysterectomy.
Educational Objective: The uterosacral ligament is a paired structure that extends bilatera ly from the cervical region to the sacrum, helping to support the uterus in the pelvis.
A 1-month-old male newborn is brought to the emergency department by his mother because of a 5-day history of vomiting after feedings. His mother says the vomiting is forceful, and appears to contain only formula. She says he seems eager to feed after each episode. He appears irritable. He is at the 25th percentile for length and weight. His temperature is 37 6DC (99.7T), pulse is 140/min: respirations are 24/min: and blood pressure is 30/40 mm Hg. Physical examination shows decreased skin turgor. Which of the following sets of serum findings (in mEq/L) is most likely in this newborn at this time?
Correct Answer: A.
Pyloric stenosis is caused by hypertrophy of the pyloric sphincter leading to gastric outlet obstruction and vomiting. It commonly presents with nonbloody; nonbilious emesis after feedings beginning around 3 to 6 weeks of age. It is more common in male infants. Symptoms may begin with occasional vomiting, then progress to projectile emesis after every feed: dehydration, and malnutrition as the stenosis worsens. Repeated bouts of vomiting can cause metabolic and electrolyte derangements, classically hypochloremic, hypokalemic metabolic alkalosis caused by losses of hydrochloric acid, a major component of stomach secretions. Metabolic alkalosis occurs secondary to dehydration and subsequent volume contraction plus relative excess of bicarbonate. Volume depletion also
eadstothe activation of the renin-angiotensin-aldosterone system, which in turn stimulates renal tubule bicarbonate reabsorption and new bicarbonate generation. Metabolic alkalosis, volume depletion, and increased concentration of aldosterone also leads to renal potassium excretion and hypokalemia. Hypokalemia also contributes to metabolic alkalosis via transcellular exchange of extracellular sodium and protons for potassium ions. Diagnosis of pyloric stenosis is typically by abdominal ultrasonography, which demonstrates thickened pyloric musculature, and treatment requires surgical pyloromyotomy.
**Educational Objective: **Pyloric stenosis is caused by hypertrophy of the pyloric sphincter, resulting in gastric outlet obstruction, which typically first presents at around 3 to 6 weeks of life. It is characterized by repeated vomiting after feeds, leading to dehydration and a hypochloremic, hypokalemic metabolic alkalosis.
A 33-year-old woman with HIV infection is brought to the emergency department 30 minutes after she had a generalized tonic-clonic seizure. She also has a 2-month history of daily headaches. Physical examination shows no signs of meningismus. Muscle
strength is 3/5 in the left upper extremity and 5/5 in the right upper extremity. Her CD4+ T-lymphocyte count is 22/mm3 (N>5G0), and plasma HIV viral load is 50?000 copies/mL. A CT scan of the head shows a 3-cm lesion in the right cerebral cortex . Serologic studies show a positive IgG antibody titer to Toxoplasma gondii. Treatment with pyrimethamine and sulfadiazine is initiated. During the next 2 weeks; she has three additional seizures. Two weeks after starting antibiotic therapy a CT scan of the head shows that the lesion has increased to 3.5 cm.. Which of the following is the most likely cause of this mass?
A) Bacterial abscess
B) Cerebral toxoplasmosis
C) Glioblastoma
D) Metastatic disease
E) Non-Hodgkin lymphoma
Correct Answer: E.
This patient with IHIV/AIDS and a solitary expanding mass in the cerebral cortex most likely has primary central nervous system (CNS) lymphoma; a variety of non-Hodgkin lymphoma and an AIDS-defining malignancy. Primary CNS lymphoma classically presents with seizures, lethargy, subacute memory loss, and headache. Physical examination may disclose neurologic deficits stemming from structural disruption as a result of the location of the mass. Risk factors include a low CD4 count (often less than 50 cells/mm3} and a high HIV viral load. Clinical suspicion for CNS lymphoma should be highest in patients with uncontrolled HIV and a newly discovered brain mass. CNS lymphoma commonly involves the deep structures of the brain (eg. basal ganglia), cerebral white matter corpus callosum, and periventricular areas. Diagnosis is made by imaging, biopsy and cerebrospinal fluid analysis. The differential diagnosis for a space-occupying brain lesion in a patient with HIV/AIDS includes cerebral toxoplasmosis, brain abscesses, malignant primary brain tumors, and metastatic disease. MRI of the brain is helpful in differentiating between these diseases. Lumbar puncture is frequently performed as part of the evaluation for suspected primary CNS lymphoma unless there is a contraindication such as impending
brain herniation. Treatment includes methotrexate and highly active antiretroviral therapy. Rituximab, a monoclonal antibody against CD20, can be used as an adjunct.
Educational Objective: Solitary brain lesions in patients with HIV/AIDS, particularly when associated with a low CD4+ count and a high viral load, should raise suspicion for primary CNS lymphoma. Alternative diagnoses include a bacterial abscess, cerebral
toxoplasmosis, primary brain tumors, and metastatic lesions.
50-year-old man with type 2 diabetes mellrtus comes to the physician for a follow-up examination. Current medications include long-acting insulin and metformin. His vital signs are within normal limits. Physical examination shows no abnormalities. His
hemoglobin Alc is 7.9%. Treatment with a third drug that promotes release of endogenous insulin is initiated to improve glucose control. This drug is most likely which of the following?
A) Acarbose
B) Miglitol
C) Pioglitazone
D ) Pramlintide
E) Sitagliptin
Correct Answer: E.
Sitagliptin is an oral antihyperglycemic used in the control of blood glucose in type 2 diabetes mellitus. It is a competitive inhibitor of dipeptidyl peptidase-4 (DPP-4). DPP-4 is the enzyme responsible for breaking down gastrointestinal incretins; which are released
during a meal and promote the secretion of insulin. By preventing the breakdown of incretin hormones by inhibiting the enzyme responsible for degrading them, their effect (increasing endogenous release of insulin) persists. Examples of incretins include glucagonike
peptide-1 (GLP-1). Sitagliptin is generally a second-line medication, used when metformin, diet, exercise, and weight loss have failed to control blood glucose appropriately (as marked by a hemoglobin A-| C above 7.0%). In some cases, insulin ora sulfonylurea may be added prior to initiating a DPP-4 inhibitor.
Educational Objective: DPP-4 inhibitors prevent the early breakdown of incretins, which promote endogenous insulin release. Sitagliptin is an example of this class of inhibitor. They are generally used once metformin, diet, exercise, weight loss, or additiona medications have failed to appropriately control a patient’s blood glucose.
Lysosomes present in hepatocytes of patients with mucolipidosis II ( l-cell disease) contain abnormal enzyme activities resulting from an inability of these cells to do which of the following?
A) Glycosylate secretory proteins
B} Recycle lysosomes
C) Recycle mannose 6-phosphate receptors from the plasma membrane
D ) Synthesize lysosomal enzymes
E) Synthesize mannose 6-phosphate residues on proteins
-
Correct Answer: E.
Mucolipidosis II, also known as l-cell (inclusion cell) disease, results from accumulation of oligosaccharides, lipids, and glycosaminoglycans such as heparan sulfate and dermatan sulfate within cells, l-cell disease is a type of lysosomal storage disease. It is similar in phenotype and pathophysiology to Hurler syndrome, l-cell disease results from a failure of Golgi-based post-translational modification of proteolytic enzymes that would typically be targeted to the lysosome. Proteases targeted to the lysosome are tagged with
phosphate at the sixth carbon on their mannose residues, forming mannose 6-phosphate. Defective Golgi W-acetylglucosaminy1-1-phosphotransferase enzymes are unable to join phosphate onto mannose residues. This causes the synthesized proteases to be abnormally routed into vesicles for exocytosis instead of to the lysosome. In absence of these proteins within the lysosome, norma cellular debris that require lysosomal degradation accumulate within the cells and cause inclusions that can be seen on light microscopy. The resulting accumulation of such products leads to widespread cellular and organ dysfunction. Signs and symptoms of l-cell disease include failure to thrive, developmental delay, coarse facial features, restricted skeletal development,
hepatosplenomegaly, cardiac structural defects, corneal clouding, and dwarfism, l-cell disease demonstrates autosomal recessive inheritance; there is no treatment for the condition other than supportive care
Educational Objective: l-cell disease is an autosomal recessive lysosomal storage disease that results from a defect in W-acetylglucosaminyl-1-phosphotransferase enzymes. This results in the failure of phosphorylation of lysosomal hydrolases, which subsequently leads to their exocytosis from the cell instead of routing to their normal site of action within the lysosome.
Which of the following curves best describes variation of follicle-stimulating hormone concentration during the menstrual cycle?
Correct Answer: B.
Follicle-stimulating hormone (FSH) is produced by the pituitary in response to gonadotropin releasing hormone from the hypothalamus. Its concentration fluctuates predictably with each menstrual cycle. At the start of the follicular phase, just after menses occurs,
FSH increases to support a developing ovarian follicle. Unlike the 14-day luteal phase, the length of the follicular phase is variable. As the follicle increases in size, it requires less support and FSH decreases slightly until ovulation occurs. Ovulation is
accompanied by a rapid surge in FSH and luteinizing hormone (LH): this marks the transition from the follicular phase to the luteal phase. FSH then rapidly subsides and increases slowly through the luteal phase as it prepares to support another ovarian follicle at
the start of the following cycle.
Incorrect Answers: A. C. D. and E.
LH (Choice A) remains low throughout the follicular phase until if surges and triggers ovulation. This marks the transition to the luteal phase, named for the presence of the corpus luteum. The corpus luteum is the structure that remains after a follicle ruptures and ovulation occurs. 11 produces estrogen and progesterone, which support the secretory endometrium and allow for implantation to occur. If implantation occurs, the corpus luteum is maintained by human chorionic gonadotropin and continues to produce
progesterone. If implantation does not occur, the carpus luteum shrinks and eventually becomes a fibrous remnant called the corpus albicans.
Progesterone (Choice C) is produced by the corpus luteum alter ovulation and maintains the secretory endometrium in order to allow for implantation to occur. If implantation does not occur, progesterone concentrations decrease and the endometrium beings to slough, causing menses. Estrogen (Choice D) is produced by the granulosa cells of the developing follicle. As the follicle increases in size through the follicular phase, its production of estrogen increases. A second, smaller peak of estrogen occurs in the luteal phase, which stimulates the endometrium to proliferate.
A hormone that fluctuates less during the overall course of the menstrual cycle is gonadotropin releasing hormone (GnRH). For example, Choice E may represent the pulsatile release of GnRH from the hypothalamus that occurs every 1 to 1 !4 hours in the
follicular phase and every two hours in the luteal phase. These small pulses stimulate the pituitary to secrete FSH and LH to drive the development of the ovarian follicle and ovulation. Educational Objective: FSH increases during the follicular phase of the menstrual cycle in order to support the developing ovarian follicle. It surges at the time of ovulafion. followed by a precipitous drop, and then subsequently slowly increases during the luteal phase, preparing to support the developing follicle of the next cycle.
A 45-year-old woman with chronic hepatitis C comes to the physician because of a 3-week history of fatigue and joint pain. Her temperature is 37.5°C (99.5°F); pulse is 88/min, and blood pressure is 155/75 mm Hg. Physical examination shows the findings in the photograph and hepatosplenomegaly. Serum studies are most likely to show an increased amount of which of the following in this patient?
A) Cholesterol
B) Complement
C) Creatine kinase
D) Cryoglobulin
E) D-Dimer
Correct Answer: D.
Cryoglobulins are immunoglobulins (or immunoglobulin-complement complexes) that precipitate out of serum. Risk factors for excessive cryoglobulin formation include chronic viral infections such as hepatitis B and C viruses, human immunodeficiency virus (HIV), malaria, and Ebstein-Barr virus (EBV), chronic inflammatory conditions such as systemic lupus erythematosus and Sjogren syndrome, and IymphoproIiterative diseases such as multiple myeloma. The deposition of the immunoglobulin-complement complexes in blood vessels results in leukocytoclastic vasculitis, which can manifest with a reddish-purple rash (purpura) and possible end-organ dysfunction. Mixed cryoglobulinemia is characterized by the triad of weakness, arthralgias, and palpable purpura. Patients may also present with peripheral neuropathy, hematuria, and hepatosplenomegaly.
Educational Objective: Increased cryoglobulin concentrations are characteristic of mixed cryoglobulinemia, which often presents with palpable purpura in association with arthralgias and peripheral neuropathy caused by immune-complex mediated vasculitis. Chronic hepatitis C virus is the most common infection associated with cryoglobulinemia.
A 69-year-old woman comes to the physician because she has had weakness of her left leg since awakening that morning. Physical examination shows weakness of the extremity. A Babinski sign is present on the left. Sensory testing shows decreased somatic sensation in the left foot, agraphesthesia on the plantar surfaces of the toes; and decreased position sense in the toes. An MRI of the brain shows an edematous area in the cerebral cortex of the right hemisphere. The most likely cause of this condition is a lesion located at which of the following labeled areas in the photographs of normal brains shown?
Correct Answer: G.
Educational Objective: The lower extremity is controlled by the medial aspects of the precentral (motor) and postcentral (sensory) gyri in the region referred to as the paracentral lobule. Strokes affecting this region result in the loss of motor and sensory function of the contralateral lower extremity
Correct Answer: D.
Rheumatoid arthritis is an autoimmune disease that causes extensive inflammation in synovial tissues. The clinical course is characterized by joint destruction, periarticular bone loss; and synovial hypertrophy, along with extra-articular manifestations such as rheumatoid nodules and skin rash. Patients often present with symmetric patterns of arthritis particularly in the wrists and hands in middle-aged women. Serologic studies generally demonstrate a positive rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. Rheumatoid arthritis is associated with the HLA-DR4 genotype.
