UWorld Review 5/3
A 32-year-old man presents with low grade fever, cough and generalized malaise. The patient has otherwise been healthy and has no significant medical history. His past surgical history includes tonsillectomy and tympanostomy tube placement at the age of 8. Careful questioning reveals that the patient recently came back from an "outdoor adventure" trip in the Great Lakes, and began feeling sick only after returning. Microscopic examination of a KOH preparation of an exudate specimen reveals a large yeast cell with a single bud. When incubated in a specific medium at 75.2ºF (24ºC), a multicellular structure with branching, tubular cells grows. The patient is most likely infected with which of the following:
Blastomyces dermatitidis - This dimorphic fungus is common in the Ohio and Mississippi River valleys as well as the Great Lakes region. It is found in soil and can cause pneumonia most commonly, but the disseminated form is common and severe. Culture (25ºC): branching hyphae. Biopsy: large, round yeasts with doubly refractile wall and single broad-based bud.
A 45-year-old woman comes to the clinic with a 3-month history of persistent shoulder and back pain and easy fatigability. She also has pain and stiffness in all her muscles that worsens in the morning and evening. She does not participate in any regular exercise because her pain is exacerbated with activity. She works as a computer programmer and reports some difficulty concentrating on her job. Past medical history is significant for depression and gastroesophageal reflux disease, but she is not currently taking any medications. Physical examination shows normal range of motion and 5/5 muscle strength in both upper and lower extremities. Soft tissue tenderness is present at several locations bilaterally above and below the waist. Which of the following is the most likely diagnosis?
Fibromyalgia - Fibromyalgia is a chronic disorder that is characterized by widespread musculoskeletal pain in association with fatigue and neuropsychiatric disturbances (eg, paresthesias, poor sleep, depression, difficulty concentrating). It is most common in women age 20-55. Examination often shows tenderness at characteristic locations in the soft tissues and at bony prominences. The diagnosis can be made in patients with chronic pain and fatigue for >3 months in the absence of physical or laboratory findings suggestive of an inflammatory etiology (eg, synovial swelling, elevated erythrocyte sedimentation rate or C-reactive protein) or other chronic pain syndrome. The precise etiology of fibromyalgia is unknown, but it likely involves abnormal central processing of painful stimuli. Possible contributing factors include genetic predisposition and physical or emotional stressors. Although exercise can temporarily exacerbate the pain of fibromyalgia, gradual incremental aerobic exercise is proven to reduce pain and improve function. Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors modify processing of pain signals and can also be considered in patients with more severe or refractory symptoms.
A 64-year-old man comes to the office due to 3 days of diarrhea. He began to have nausea, vomiting, abdominal cramps, and diarrhea 24 hours after eating chicken salad at a fast-food restaurant. The patient has had 4-6 episodes of diarrhea per day with no blood in the stool. He has no tenesmus. His wife, who ate the same food, had a few loose stools but felt well afterward. The patient takes a tumor necrosis factor inhibitor for psoriatic arthritis and a proton pump inhibitor for gastritis. Temperature is 38 C (100 F), blood pressure is 120/70 mm Hg, and pulse is 88/min. Abdominal examination reveals mild diffuse tenderness to palpation and increased bowel sounds. Cultures of the stool yield gram-negative bacilli that are nonlactose fermenting and oxidase negative. Which of the following is the most likely complication associated with this patient's current infection?
Osteomyelitis - This patient with diarrhea has stool cultures growing gram-negative bacilli that are nonlactose fermenting and oxidase negative, findings consistent with nontyphoidal Salmonella gastroenteritis. Transmission typically occurs via consumption of contaminated poultry products (eg, chicken salad), including eggs. Ingested Salmonella must survive the acidic environment of the stomach prior to traveling to the small intestine to cause disease. Therefore, patients on acid suppression (eg, proton pump inhibitors) require smaller infectious doses and are at greater risk. Once in the small intestine, the organism penetrates enterocytes and elicits a profound inflammatory response, which is typically limited to the gastrointestinal tract. Symptoms (eg, fever, diarrhea) usually resolve within days in healthy, immunocompetent patients; however, invasive disease is more likely in patients at extremes of age and in those with impaired immunity (eg, AIDS, tumor necrosis factor-alpha inhibitor). Rather than confinement within the small intestine, bacteria can spread through the bloodstream and reticuloendothelial system (similar to typhoidal Salmonella). Sites of extraintestinal nontyphoidal Salmonella infection include the vasculature (mycotic aneurysm), heart (endocarditis), and bone. Osteomyelitis usually develops at sites of prior bone injury/prosthesis; it also occurs more commonly in patients with sickle cell disease.
A 73-year-old woman comes to the emergency department with a 3-day history of worsening breathlessness and cough productive of thick, rust-colored sputum. The patient has a longstanding history of hypertension. Temperature is 38.3 C (101 F), blood pressure is 130/68 mm Hg, pulse is 102/min, and respirations are 24/min. BMI is 27 kg/m2. Jugular venous pressure is normal and there is no lower extremity edema. Heart sounds are normal with no murmur. Lung auscultation reveals left lower lobe crackles and bronchial breath sounds. Leukocyte count is 14,000/mm3 with 80% neutrophils and 7% bands, hemoglobin is 13.6 g/dL, and platelets are 400,000/mm3. Serum levels of which of the following are most likely to be elevated in this patient?
Procalcitonin - Acute phase reactants (APRs) are proteins whose serum concentrations change by ≥25% during periods of inflammation. Several APRs have diagnostic and prognostic utility and can be interpreted on the basis of serum concentrations: Positive APRs (serum levels rise in acute inflammatory states) include fibrinogen, C-reactive protein, ferritin, hepcidin, ceruloplasmin, haptoglobin, von Willebrand factor, and complement. The erythrocyte sedimentation rate (the time required for erythrocytes to settle from suspension) is an indirect measure of positive APRs. Negative APRs (serum levels fall in acute inflammatory states) include albumin, transferrin, and transthyretin (prealbumin). Procalcitonin, a precursor of calcitonin produced by monocytes and the C cells of the thyroid, is a unique APR that has positive and negative properties. Levels rise in response to bacterial toxins and fall in response to viral infections, and therefore levels can suggest the etiology of community-acquired pneumonia. This patient has lobar pneumonia manifesting with fever, rust-colored sputum, and neutrophil-predominant leukocytosis, likely due to a bacterial infection (eg, Streptococcus pneumoniae). Therefore, procalcitonin levels are expected to be elevated.
A 65-year-old woman comes to the office to discuss pain at the posterior chest wall. She was seen 4 months ago for acute shingles involving a right mid-thoracic dermatome. The patient was not treated at that time because she had a delayed presentation and the lesions were already well-crusted and healing. The skin lesions subsequently cleared completely. However, since then, she has had persistent burning and stabbing pain in the same region that has now become severe. She has tried oral acetaminophen without relief. During discussion of treatment options, the patient says she does not want any systemic medications due to concerns about possible side effects. She is started on topical capsaicin cream, and her pain improves markedly over the next several days. Decreased activity of which of the following neurotransmitters is most likely associated with pain relief in this patient?
Substance P - Shingles is due to reactivation of latent varicella zoster virus in sensory ganglia. It causes a vesicular rash and acute neuritis due to injury to the nerves. The initial pain fades within a few weeks to months, but a subset of patients will have residual neuropathic pain in the affected dermatome. This pain, termed postherpetic neuralgia (PHN), relates to sensitization of afferent nerves in the dorsal horn. It may last several months or longer, and has a burning, stabbing, or gnawing character. PHN is usually managed with tricyclic antidepressants (eg, amitriptyline) or anticonvulsants (eg, gabapentin, pregabalin), but nonsystemic options for PHN include lidocaine patches or topical capsaicin. Capsaicin is an irritant found in the chili pepper family. It causes excessive activation of TRPV1 (a transmembrane cation channel), causing a buildup of intracellular calcium that results in long-lasting dysfunction of nociceptive nerve fibers (defunctionalization). In addition, capsaicin causes release and subsequent depletion of substance P, a polypeptide neurotransmitter involved in transmission of pain signals. On initial application, topical capsaicin causes burning, stinging, and erythema, but persistent exposure leads to a moderate reduction in pain over time.
A 62-year-old man dies suddenly in his sleep. The patient had a history of type 2 diabetes mellitus and hypertension, and he smoked a pack of cigarettes daily for 25 years. His adherence to medical care was poor. Autopsy is performed, and a histologic section of his left ventricular myocardium is shown. Which of the following directly promotes the formation of the tissue indicated by the arrow?
Transforming growth factor beta - This patient's autopsy shows a large area of fibrosis replacing myocardium, consistent with scar tissue from a resolved myocardial infarction (MI). Myocardial tissue damage due to ischemia initiates a series of changes that are analogous to cutaneous wound healing: Inflammation: Hours to days post-MI, neutrophils and macrophages remove necrotic tissue and release cytokines and growth factors that initiate tissue proliferation. Proliferation: Days to weeks post-MI, transforming growth factor-beta (TGF-β) and other anti-inflammatory cytokines downregulate the inflammatory response and stimulate fibroblast migration and proliferation, causing extensive type I and III collagen deposition. Remodeling: Weeks to months post-MI, TGF-β also stimulates production of matrix metalloproteinases (MMPs) that facilitate collagen remodeling (ie, fiber rearrangement) and crosslinking to form dense scar tissue.
A 22-year-old woman with no prenatal care has a normal vaginal delivery. On physical examination, the infant's external genitalia are atypical and ambiguous. There is an intermediate clitorophallic length and a perineal urethral opening. Well-circumscribed, mobile masses are palpable bilaterally in the inguinal area. Vital signs are normal. Serum testosterone level is within normal limits. A karyotype is performed and shows 46,XY. This infant most likely has a deficiency in which of the following enzymes?
5α-reductase - Sexual development is influenced predominantly by 3 steroid hormones: Testosterone: development of internal male genitalia (except prostate), spermatogenesis, male sexual differentiation at puberty (eg, muscle mass, libido) Dihydrotestosterone (DHT): development of external male genitalia, growth of prostate, male-pattern hair growth; also amplifies effects of testosterone due to high affinity for testosterone receptor Estrogen: endometrial proliferation, development of ovarian granulosa cells, breast development 5α-reductase converts testosterone to DHT. There are 2 types of 5α-reductase: type 1 is present in postpubescent skin, whereas type 2 is found predominantly in the genitals. 5α-reductase type 2 deficiency results in diminished conversion of testosterone to DHT in the male urogenital tract. In the phenotypically (46,XY) male fetus with this genetic defect, the internal genitalia (ie, testes) develop normally under the influence of testosterone. However, due to the lack of DHT, the testicles remain undescended (cryptorchid testes presenting as inguinal masses) and the external genitalia do not develop properly, ranging from a small phallus with hypospadias to ambiguous or female-type genitalia.
A 55-year-old, previously healthy man is brought to the office by his wife after being forced into early retirement due to poor work performance. The patient was a financial planner but began missing important deadlines and mismanaging his client's accounts 6 months ago. He became more irritable during this time and started to curse at and insult his coworkers when they expressed concern about his performance. The patient has also become verbally abusive toward his wife but appears indifferent to the hurt he causes. She has had to take over the finances and grocery shopping. She adds, "My husband has developed quite the sweet tooth. He eats almost two boxes of cookies a day now." Physical examination is unremarkable. This patient is most likely to have which of the following neuropathologic findings?
Aggregations of phosphorylated tau protein - This patient with impaired executive function (eg, poor work performance) most likely has frontotemporal dementia (FTD), a type of early-onset dementia characterized by prominent behavioral changes. These can include: Disinhibition: socially inappropriate behavior (eg, cursing at coworkers) Apathy/loss of empathy: loss of interest in activities and/or impaired social relationships (eg, indifference toward being verbally abusive) Hyperorality: changes in diet, often with a preference for sweets; more severe manifestations include binge eating (eg, eating 2 boxes of cookies per day) or consuming inedible objects Compulsive behaviors: may include simple (eg, repetitive speech or motions) or complex (eg, hoarding, following a new religion) behaviors FTD is characterized by degeneration of the prefrontal cortex, progressing to include the anterior temporal lobes. Neuropathologic features often overlap with other neurodegenerative conditions and may include: Aggregations of phosphorylated tau protein: Tau is a protein associated with neuronal microtubules, and it normally takes part in microtubule stabilization. In patients with FTD, tau becomes hyperphosphorylated and disassociates from the microtubules, which may lead to instability and disrupted axonal transport. Phosphorylated tau aggregates to form inclusions that can appear as neurofibrillary tangles (similar to those seen in Alzheimer disease) or round inclusions (ie, Pick bodies). Abnormal TDP-43 protein inclusions: TDP-43 is a protein involved in DNA repair and transcription, and it becomes abnormally ubiquitinated in FTD. Pathologic TDP-43 is also found in patients with amyotrophic lateral sclerosis.
A 45-year-old man comes to the emergency department due to severe dyspnea and chest discomfort that began earlier in the day. The dyspnea has been worsening throughout the day and has been present at rest. He reports no inciting trauma. The patient has no other medical conditions and takes no medications. He has a 20-pack-year smoking history and does not use alcohol or illicit drugs. Temperature is 36.7 C (98 F), blood pressure is 110/60 mm Hg, and pulse is 96/min. Arterial blood gas drawn on room air shows an arterial partial pressure of oxygen (PaO2) of 54 mm Hg and an arterial partial pressure of carbon dioxide (PaCO2) of 26 mm Hg. Which of the following processes is most likely occurring in this patient?
Alveolar hyperventilation - This patient with acute-onset dyspnea and chest discomfort likely has an acute pulmonary embolism (PE). PE leads to increased dead-space ventilation with a consequent ventilation/perfusion (V/Q) mismatch that causes hypoxemia. The acute hypoxemia along with pulmonary parenchymal inflammation triggers an increase in respiratory drive and hyperventilation. Because the rate of CO2 removal is closely tied to ventilation rate, alveolar hyperventilation leads to increased expiration of CO2 with resulting hypocapnia (low arterial partial pressure of carbon dioxide [PaCO2]) and respiratory alkalosis. In contrast, the rate of O2 absorption becomes capped once hemoglobin is saturated, which occurs at relatively low arterial partial pressure of oxygen (PaO2) levels (eg, hemoglobin is 85% saturated at PaO2 50 mm Hg). Therefore, the blood in highly ventilated lung regions cannot absorb extra O2 to compensate for poorly ventilated regions, and hyperventilation does not significantly increase PaO2. It follows that patients with an acute V/Q mismatch (eg, due to PE or pneumonia) typically have hypocapnia with respiratory alkalosis and persistent hypoxemia. Without treatment, prolonged hyperventilation can lead to respiratory muscle fatigue with consequent respiratory failure; these patients will have hypoventilation with hypercapnia and respiratory acidosis.
A 4-day-old boy is brought to the office due to a 2-day history of progressive jaundice. The patient was born at term following an uncomplicated pregnancy. He is formula fed. The patient and his mother are both blood group A, Rh-positive. Vital signs are normal. Examination shows scleral icterus and jaundice over the face and chest. Laboratory results are as follows: Hemoglobin17.5 g/dLTotal bilirubin8 mg/dLIndirect bilirubin 7.2 mg/dL The patient is followed closely, and the jaundice resolves without intervention in 3 days. This patient's jaundice was most likely the result of which of the following changes in bilirubin metabolism compared to an adult?
Bilirubin production: increased Bilirubin conjugation: decreased Enterohepatic bilirubin circulation: increased Normally, unconjugated bilirubin is released into the bloodstream upon breakdown of red blood cells (RBCs) and taken up by the liver. Hepatic UDP glucuronosyltransferase then conjugates bilirubin, which is secreted into bile and excreted into the intestines. Bacterial enzymes in the intestines then reduce bilirubin to urobilinogen, allowing for excretion through the urine and stool. Benign neonatal hyperbilirubinemia is caused by several physiologic differences in bilirubin metabolism in newborns as compared to those in older children and adults. First, bilirubin production is increased due to increased breakdown of fetal RBCs, which are high in number (hematocrit up to 60%) and have a shorter life span (90 days as compared to 120 days in adults). Second, bilirubin conjugation is decreased due to physiologically lower levels of UDP glucuronosyltransferase in the immature neonatal liver. Finally, relative gut sterility in newborns results in decreased reduction of bilirubin to urobilinogen; instead, intestinal β-glucuronidase (which is synthesized both endogenously and by gut bacteria) deconjugates the bilirubin which allows it to be reabsorbed, therefore increasing enterohepatic circulation.
A 77-year-old man is brought to the emergency department due to acute-onset chest pain, shortness of breath, and syncope. Medical history is significant for coronary artery disease, which was treated with right coronary artery stenting 5 years ago. The patient develops cardiac arrest and resuscitation is unsuccessful. Autopsy shows a large bilateral pulmonary embolism occluding the pulmonary trunk. Further history obtained from the patient's wife indicates that he has had constant back pain over the past few months. Autopsy of the vertebrae is shown. Histologic examination of the bone lesions in this patient would most likely show which of the following?
Cells with enlarged nuclei and prominent nucleoli forming irregular glands -This patient's vertebral body bony lesions raise strong suspicion for osteoblastic metastases due to prostate adenocarcinoma; his massive pulmonary embolism was likely precipitated by an underlying hypercoagulable state of malignancy. Prostate cancer is the most common non-skin cancer in men, and risk is strongly linked to advancing age. Because most cases develop in the periphery of the prostate gland, urinary symptoms are uncommon until late in the disease course; therefore, the diagnosis is usually prompted by elevated prostate-specific antigen level, abnormal digital rectal examination, or symptoms related to advanced disease (eg, bone pain). Prostate cancer preferentially metastasizes to bone due to specific adhesion molecules (eg, CXCR4) and receptor ligands (eg, RANK) on the cancer cell surface that adhere to pericytes and bone marrow stromal cells. After it establishes a nidus, the tumor secretes osteoblast differentiation factors (eg, endothelin 1, insulin-like growth factors, platelet-derived growth factors, bone morphogenic proteins) that promote new bone growth. Biopsy of a bone lesion would most likely show disordered trabecular growth and evidence of prostate cancer cells such as irregular glands with enlarged nuclei and prominent nucleoli.
A 63-year-old woman comes to the office for a routine preventive examination. She has no significant medical problems and takes no medications. The patient consumes a balanced diet; gets regular exercise; and does not use tobacco, alcohol, or illicit drugs. She is up to date on breast, colon, cervical, and lipid screenings. Her physical examination findings are unremarkable. The patient expresses concern about wrinkles around her eyes that make her "look old." A decrease in which of the following is most likely responsible for this patient's complaint?
Collagen fibril production - Multiple environmental factors, especially exposure to ultraviolet (UV) light, contribute to aging of the skin. UVB wavelengths are predominantly absorbed in the upper dermis and contribute to sunburn and increased risk of malignancy. UVA wavelengths penetrate deeper into skin and cause photoaging. UVA produces reactive oxygen species, which activate multiple inflammatory cell-surface receptors and nuclear transcription factors. This leads to decreased collagen fibril production, along with upregulation of matrix metalloproteinases (including collagenases) that subsequently degrade type I and III collagen and elastin. Photoaging may be visible by age 30-35. Gradual thinning of the epidermis is seen, with reduction in subcutaneous fat, blood vessels, hair follicles, sweat ducts, and sebaceous glands. Rete ridges at the dermoepidermal junction become flattened. This loss of subcutaneous tissue causes the skin to become atrophic and more vulnerable to damage. In addition, there is increased crosslinking of collagen, with deposition of collagen breakdown products. The atrophic dermis and increased collagen crosslinking, along with desiccation of the stratum corneum, produce the characteristic wrinkling of photoaged skin.
A microbiologist performs a genetic experiment in which cultures of Escherichia coli are treated with a chemical that induces a high frequency of mutations. Individual bacterial colonies are isolated to identify a mutant strain that lacks a specific enzyme involved in DNA replication. This specific enzyme is responsible for removing short fragments of RNA that are base paired to the DNA template. Which of the following enzymes is most likely deficient in this strain of E coli?
DNA Polymerase I - Bacterial DNA replication is coordinated by the actions of multiple enzymes and proteins. Before DNA synthesis begins, helicase binds double-stranded DNA at the origin of replication with the assistance of DnaA protein, forming a replication fork that unwinds and separates the DNA. Single-stranded DNA-binding protein then attaches to the separated strands to prevent their reannealing. Unwinding and separation of DNA produces positive supercoils that can lead to DNA fracture if not relieved. Topoisomerase II (DNA gyrase) relieves the tension created during unwinding by introducing negative supercoils into the DNA. Before DNA polymerase III can begin elongating a new DNA strand, it requires an RNA primer made up of short RNA sequences base-paired to the parent DNA. This primer is synthesized by the enzyme primase (DNA-dependent RNA polymerase). DNA synthesis then proceeds in the 5' to 3' direction with the leading strand being formed continuously toward the replication fork and the lagging strand being formed discontinuously away from the replication fork. Replication of the lagging strand results in the formation of numerous short DNA segments called Okazaki fragments. These fragments are ultimately bound together by the enzyme ligase after their RNA primers have been removed and replaced with DNA. The removal of RNA primers and their replacement with DNA is accomplished by DNA polymerase I, the only bacterial DNA polymerase with 5' to 3' exonuclease activity. DNA polymerase III has 5' to 3' polymerase and 3' to 5' exonuclease ("proofreading") activity; however, it cannot remove RNA primers as it lacks 5' to 3' exonuclease activity.
A 57-year-old woman comes to the emergency department due to cough and hemoptysis. The patient also reports several months of fatigue and joint pain. Physical examination is notable for crusting of the nasal mucosa, lung crackles, and scattered palpable purpura over the lower extremities. Chest x-ray reveals bilateral, diffuse alveolar infiltrates. Laboratory studies show normocytic anemia, red blood cell casts and protein in the urine, and positive c-ANCA. After a confirmatory biopsy, treatment with rituximab infusion is planned. This medication is most likely to improve this patient's condition via which of the following mechanisms?
Depletion of B cells - This patient's clinical picture is consistent with granulomatosis with polyangiitis (GPA), a c-ANCA-positive inflammatory vasculitis that primarily attacks the upper/lower respiratory tract, kidneys, and skin. Molecular and immunologic advances have led to a dramatic expansion in treatments for chronic systemic inflammatory diseases such as GPA; treatments are generally classified as follows: Cytokine inhibitors: These bind free inflammatory cytokines or block cytokine receptors on cell surfaces; they target tumor necrosis factor (eg, infliximab, etanercept), IL-1, IL-6, IL-17, or IL-12/23. T-cell costimulation inhibitors: Two steps are required to activate cytotoxic T cells. The T cell must bind a specific antigen on the major histocompatibility complex type 1 of an antigen-presenting cell, and then the T cell must be costimulated by the interaction between the T-cell surface receptor CD28 and the antigen-presenting cell surface ligand CD80/86. T-cell costimulatory inhibitors (eg, abatacept) block the CD28 receptor on the cytotoxic T cell, which prevents T-cell costimulation and causes T-cell anergy. B-cell depletion or inhibition: Because B cells generate inflammatory cytokines, promote T-cell activation, and differentiate into plasma cells that generate autoantibodies, medications that inhibit B-cell activation (eg, belimumab) or deplete B-cell populations (eg, rituximab) are highly effective in many systemic inflammatory disorders. Rituximab is an IgG monoclonal antibody against CD20, a surface molecule present on developing and mature B cells. Binding of rituximab to CD20 results in Fc receptor-mediated B-cell cytotoxicity and antibody-dependent B-cell phagocytosis, which significantly reduces the B-cell population. Although existing plasma cells are unaffected (they do not express CD20), the reduction in total B-cell population significantly improves inflammatory symptoms. However, depletion of B cells also increases the risk for severe and recurrent bacterial infections, a major adverse effect of therapy.
An 80-year-old woman is evaluated for blisters that have developed on both feet over the past week. The patient lives in a nursing home due to dementia but has no other chronic medical conditions and takes no medication. Vital signs are within normal limits. There are no oral lesions. Examination findings are shown in the exhibit. Which of the following is most likely involved in the pathogenesis of this patient's condition?
Deposition of IgG and complement at the dermal-epidermal junction - This elderly patient has the typical features of bullous pemphigoid (BP), an autoimmune blistering disease. BP most commonly affects individuals age >60 and is more common in those with neurologic disorders (eg, Alzheimer dementia). As in this patient, bullae are typically tense and have erythematous or normal-appearing bases. Lesion distribution can be localized or diffuse, involving the trunk and extremities; mucosal involvement is rare. BP is caused by antibodies against hemidesmosomes along the basement membrane of the dermal-epidermal junction. These autoantibodies result in a destructive inflammatory cascade that causes the entire epidermis to separate from the dermis, forming subepidermal blisters. Immunofluorescence shows IgG and/or C3 deposits in a linear pattern along the basement membrane.
A 54-year-old man comes to the emergency department with pain and swelling in the right leg. The patient has no other medical problems and takes no medications. He has smoked a pack of cigarettes daily for the past 30 years. He is a business executive and just returned from an overseas trip. Physical examination shows pitting edema of the right leg and tenderness on deep palpation of the calf muscles. Peripheral pulses are symmetric and full. He is started on a medication that prolongs activated partial thromboplastin time and prothrombin time in a dose-dependent manner but has no effect on thrombin time. Which of the following agents was this patient most likely administered?
Direct factor Xa inhibitor - This patient has deep venous thrombosis, which is typically treated with anticoagulation therapy for >3 months to prevent recurrent thrombosis. Initial treatment is often with heparin agents (eg, unfractionated heparin, low-molecular-weight heparin, fondaparinux), followed by bridging to an oral anticoagulant (most commonly warfarin). Additional treatment options include direct factor Xa inhibitors (eg, apixaban, rivaroxaban) and direct thrombin inhibitors (eg, dabigatran). In general, medications that affect the extrinsic pathway prolong the prothrombin time (PT), whereas inhibition of the intrinsic pathway mainly prolongs the activated partial thromboplastin time (aPTT). The thrombin time (TT) is prolonged with medications that directly or indirectly inhibit thrombin. Because factor Xa is located at the junction of the intrinsic and extrinsic pathways, direct factor Xa inhibitors prolong both aPTT and PT with no effect on TT.
A 23-year-old man is brought to the emergency department after sustaining stab injuries in a street fight. The patient feels lightheaded and dizzy. His blood pressure is 100/60 mm Hg and pulse is 115/min. Physical examination shows profuse bleeding from penetrating wounds over the left neck and shoulder area. Intravenous fluids are administered, and a blood transfusion is initiated. Urgent surgical exploration is performed, and the injured blood vessel is repaired. Further exploration shows complete transection of the nerve indicated. Which of the following actions is most likely to be weakened as a result of this patient's nerve injury?
Extension of the wrist - The radial nerve is the largest branch of the brachial plexus and receives fibers from C5-T1. It innervates all of the extensor muscles of the upper limb below the shoulder and provides sensory innervation to the skin of the posterior arm, forearm, and dorsal lateral hand. This nerve tracks within the radial groove on the humerus; therefore, it is vulnerable to traumatic injury (eg, penetrating stab wound) at the humeral midshaft. The nerve can also be injured during its superficial course within the axilla. Patients with proximal radial neuropathy typically have weakness during wrist and finger extension (wrist drop) and variable sensory loss over the posterior arm and forearm.
A 33-year-old primigravida comes to the office to discuss the results of prenatal testing. The patient is at 16 weeks gestation. Maternal serum alpha-fetoprotein is reduced, and ultrasound reveals increased nuchal translucency. Amniocentesis shows a fetal karyotype of 47,XX,+21. This fetus is at greatest risk of having which of the following embryologic malformations?
Failure of recanalization within the intestines - Down syndrome (trisomy 21) is the most common trisomy in liveborn infants. The diagnosis is often suspected following abnormal prenatal screening (eg, increased nuchal translucency on ultrasound, decreased maternal serum alpha-fetoprotein [AFP]) and confirmed by chorionic villous sampling or amniocentesis. Most cases are caused by maternal meiotic nondisjunction, which results in 3 complete fetal copies of chromosome 21. The risk for meiotic nondisjunction increases with maternal age, and women age ≥35 are at highest risk. The most common gastrointestinal abnormality associated with Down syndrome is duodenal atresia. Normally, in early gestation, epithelial proliferation briefly occludes the intestinal lumen and is followed by recanalization. Failure of the duodenal lumen to recanalize results in duodenal atresia and intestinal obstruction. During the first few days of life, infants classically have bilious emesis, and x-ray findings include the double bubble sign, which represents the dilated stomach and proximal duodenum.
A 34-year-old woman is found dead in her apartment. An autopsy examination is performed. A ruptured plaque in the proximal anterior descending artery with an overlying occlusive thrombus is found. Incidentally, a 4-cm hepatic mass in the right lobe of the liver is also found. Grossly, the mass is well demarcated from the surrounding liver tissue and appears nodular with a central, gray-white, depressed stellate scar from which fibrous septa radiate to the periphery. The rest of the liver is normal. No additional abnormalities are noted on autopsy. Which of the following is the most likely diagnosis of this patient's liver lesion?
Focal nodular hyperplasia - This patient's incidentally found liver mass is characteristic of focal nodular hyperplasia (FNH), a nonneoplastic lesion that most commonly occurs in young women. FNH is thought to result from a hepatic vascular abnormality causing localized hyperperfusion with a secondary hyperplastic response. It grossly appears as a well-circumscribed, solitary mass with a characteristic central stellate scar from which fibrous septa radiate to the periphery. On microscopic examination, the fibrous septa—which enclose abnormally large, thick-walled arterial branches—divide the lesion into nodules composed of plates of normal-appearing hepatocytes. FNH is benign and typically does not enlarge, undergo malignant transformation, or rupture; therefore, most cases do not require treatment. These lesions are usually asymptomatic and discovered incidentally during autopsy examination or abdominal imaging for a different condition.
A researcher conducts a study to evaluate the morphological changes of various cerebral pathologies using live animal models. In an experiment, histopathological examination of the brain after an inciting event shows neurons with intensely eosinophilic cytoplasm and condensed basophilic nuclei. Serial biopsies are obtained to evaluate progressive changes. Which of the following is most likely to be seen in the affected brain area in the subsequent weeks?
Glial cell hyperplasia - The histopathological findings of neurons with shrunken, basophilic nuclei and intensely eosinophilic cytoplasm (red neurons) are indicative of irreversible neuronal damage. In response to irreversible injury and neuronal death, astrocytes proliferate at the site of injury to restore tissue integrity (a role analogous to fibroblasts outside the CNS). This process is called astrocytosis (or gliosis) and is a universal response of the CNS to severe damage. As astrocytes proliferate, they replace lost neurons, compensate for their volume, and over time form a closely connected, firm meshwork called a gliotic scar.
A 41-year-old woman with a long history of heavy menstrual bleeding comes to the office for follow-up. Two weeks ago, the patient was diagnosed with iron deficiency anemia and was started on oral ferrous sulfate. Today, vital signs and physical examination are unremarkable. Laboratory evaluation shows an appropriate response to the medication with an increase in reticulocyte production. She is instructed to continue iron supplementation. The woman is concerned about iron buildup and damage to vital organs if she continues to take the medication. She is reassured that iron homeostasis is closely regulated; as the body's iron stores increase, a hormone is released and functions in reducing the amount of dietary iron absorbed from the intestines. Which of the following cells is most likely responsible for secreting this hormone?
Hepatic parenchymal cells - Hepcidin is an acute phase reactant synthesized by hepatic parenchymal cells that acts as the central regulator of iron homeostasis. High iron levels and inflammatory conditions increase the synthesis of hepcidin, while hypoxia and increased erythropoiesis act to lower hepcidin levels. Hepcidin influences body iron storage through its interaction with ferroportin, a transmembrane protein responsible for transferring intracellular iron to the circulation. Upon binding hepcidin, ferroportin is internalized and degraded, decreasing intestinal iron absorption and inhibiting the release of iron by macrophages.
A 39-year-old man is brought to the office by his wife who is concerned about his behavior over the past year. She says, "He used to be outgoing and upbeat, but now he seems uncharacteristically depressed and distant from the family. He has lost interest in his work and has difficulty making decisions." Over the past month, he has become increasingly paranoid and believes that his business partner is trying to kill him. The patient has no psychiatric history. Both his father and grandfather were hospitalized in long-term care facilities and died in their 50s. Physical examination shows random, abrupt, uncoordinated movements of the left leg. On mental status examination the patient is restless and irritable. He is convinced that not only his business partner but also the government is out to harm him. Which of the following is the most likely diagnosis?
Huntington disease - This patient's development of psychiatric symptoms in his late-30s, abnormal choreiform movements (rapid and unpredictable contractions affecting mostly distal limbs), and family history are suggestive of Huntington disease (HD). HD is an autosomal dominant, progressive neurodegenerative disorder characterized by chorea, psychiatric symptoms, and subsequent dementia. Onset in mid-life is most common. There is no known cure and treatment is symptomatic. Psychiatric symptoms are highly prevalent in HD and may occur prior to the onset of chorea. They may include irritability, anxiety, apathy, depression, and psychosis (eg, delusions, hallucinations). Dementia develops later in the disease course and is characterized by prominent executive dysfunction. The diagnosis of HD is confirmed by testing for trinucleotide (cytosine-adenine-guanine [CAG]) repeat expansion in the huntingtin (HTT) gene.
A 57-year-old man comes to the office for a follow-up appointment. He has a history of systolic heart failure, which has been managed with appropriate medical therapy. The patient experiences significant functional impairment at baseline and is able to walk only short distances. His most recent echocardiogram revealed a left ventricular ejection fraction of 30% (normal ≥55%). The physician decides to add spironolactone to the treatment regimen. The addition of this medication is most likely to cause a decrease in which of the following?
Hydrogen ion secretion from the collecting duct - Aldosterone is a mineralocorticoid produced by the adrenal zona glomerulosa in response to hypotension and reduced renal blood flow (renin-angiotensin-aldosterone system). Hyperkalemia can also stimulate aldosterone secretion. Aldosterone acts primarily in the collecting duct, where it increases the number of basolateral Na+/K+-ATPase pumps and apical sodium channels on principal cells, increasing sodium and water reabsorption. It also promotes potassium and hydrogen ion secretion from the principal and intercalated cells, respectively. Aldosterone receptor antagonists (eg, spironolactone, eplerenone) inhibit the effects of aldosterone and reduce sodium reabsorption and potassium and hydrogen ion secretion in the collecting duct. Benefits include enhanced diuresis and lower blood pressure. Adverse effects of these medications include hyperkalemia, hyponatremia, metabolic acidosis, and gynecomastia (with spironolactone, which also inhibits the testosterone receptor).
A 72-year-old man comes to the emergency department due to severe chest tightness and dyspnea that started 20 minutes ago at a family dinner. He has never experienced similar symptoms before. The patient's medical conditions include hypertension, hyperlipidemia, type 2 diabetes mellitus, and prostate cancer. He takes multiple medications and has no drug allergies. The patient smoked a pack of cigarettes daily for 30 years but stopped smoking 10 years ago. Chest CT scan with contrast is shown.Which of the following factors most likely contributed to this patient's current condition?
Hypercoagulability - This patient is experiencing sudden-onset chest tightness and dyspnea, and CT scan of the chest shows a saddle pulmonary embolism (PE) straddling the bifurcation of the main pulmonary artery. The main pulmonary artery, usually comparable in diameter to the ascending aorta, is significantly dilated due to the proximal increase in hydrostatic pressure from the PE. Saddle PE can result in sudden cardiac death or severe hypotension, but many patients can be hemodynamically stable on presentation. Venous thromboembolism (VTE) (ie, PE or deep venous thrombosis) results from the Virchow triad of endothelial injury, venous stasis, and a hypercoagulable state. Malignancy (eg, prostate cancer) induces a hypercoagulable state and is a strong risk factor for VTE. Active smoking is also a risk factor as it contributes to endothelial injury and a hypercoagulable state. Age plays a role as well, as older individuals tend to be more sedentary and are more prone to venous stasis.
A 29-year-old woman, gravida 2 para 2, comes to the emergency department with fever, crampy abdominal pain, and right flank pain 8 days after an uncomplicated vaginal delivery. Temperature is 38.3 C (101 F) and blood pressure is 110/60 mm Hg. Physical examination shows tenderness in the right lower quadrant and flank. The patient is hospitalized and started on intravenous antibiotics for presumed postpartum endometritis, but her fever persists. Urine and blood cultures show no bacterial growth. CT scan of the abdomen and pelvis reveals right ovarian vein thrombosis. If this patient remains untreated, she is at risk for extension of the thrombus into which of the following vessels?
Inferior vena cava - Ovarian vein thrombosis occurs when a thrombus forms in the ovarian vein and becomes infected (eg, septic pelvic thrombophlebitis). It is a rare complication associated with the postpartum period, pelvic surgery, or malignancy. The classic presentation is persistent fever and focal abdominal pain despite broad-spectrum antibiotics. Ovarian vein thrombosis is more commonly right sided (90%) due to greater tortuosity of the right ovarian vein. In addition, peripartum dextrorotation of the uterus (rotation of the uterus to the right due to presence of the colon) increases compression on the right ovarian vein, thereby increasing the risk of thrombosis. Because ovarian venous drainage is asymmetric, the laterality of the affected ovarian vein determines which other vessels are at risk for thrombus extension. The right ovarian vein drains directly to the inferior vena cava (IVC), whereas the left ovarian vein drains first into the left renal vein, which then drains to the IVC.
A 75-year-old hospitalized man is evaluated for abdominal pain and fever. The patient was admitted 2 weeks ago due to necrotizing fasciitis of the gluteal region and severe sepsis. He has been treated with surgical debridements, intravenous antibiotics, and fluids. For the past 2 days, the patient has had right upper quadrant abdominal pain, nausea, and recurrent fever. He has a history of hypertension, type 2 diabetes mellitus, and chronic obstructive pulmonary disease. His temperature is 38.8 C (102 F). Physical examination shows marked tenderness over the right subcostal area. Leukocyte count is 18,000/mm3 compared to 9,600/mm3 2 days ago. Laparoscopic surgery is planned. Which of the following will most likely be found during this patient's surgery?
Inflamed and enlarged gallbladder - This patient likely has acute acalculous cholecystitis, an acute inflammation of the gallbladder in the absence of gallstones. Acalculous cholecystitis most commonly occurs in critically ill patients (eg, those with sepsis, severe burns, trauma, immunosuppression) and is associated with high mortality. The condition is thought to arise secondary to gallbladder stasis and ischemia, which cause inflammation of and injury to the gallbladder wall. Clinical manifestations may be subtle, especially in those who are sedated or intubated. Fever, right upper quadrant pain, a positive Murphy's sign, leukocytosis, and mild elevations in liver function tests are often present. Physical examination may demonstrate jaundice and a palpable right upper quadrant mass. The diagnostic study of choice is an ultrasound, which may show signs of acute cholecystitis (eg, an edematous and enlarged gallbladder) and no gallstones.
A 64-year-old man presents to the office with chest discomfort and mild shortness of breath that started one hour ago after an argument with his wife. He has a long history of hypertension and diabetes mellitus. His blood pressure is 180/100 mmHg and his heart rate is 100/min. An EKG taken in the emergency department shows no signs of acute ischemia. Cardiac auscultation in the left decubitus position on full expiration reveals a presystolic sound. Which of the following best explains this physical examination finding?
Left ventricular hypertrophy - An S4 is an isolated presystolic (late diastolic) sound heard just prior to S1. An S4 is caused by left atrial contraction that forces atrial blood into a poorly compliant left ventricle (LV) that is nearly filled to capacity. When blood is forced into the ventricle by the atrium under these conditions it generates a large, rapid increase in LV pressure thereby producing a sound possibly resulting from rapid deceleration of the forced blood or from impact of the filling ventricle with the chest wall. LV hypertrophy and other causes of diastolic heart failure therefore favor generation of an S4 sound. This patient's LV hypertrophy is likely secondary to chronic hypertension.
A 31-year-old man is hospitalized after sustaining multiple injuries during a motor vehicle collision. The patient is not conscious initially, and no information is available regarding his medical history. Two days after initial hospitalization, he experiences palpitations and difficulty sleeping. Shortly thereafter, the patient suffers a generalized tonic-clonic seizure. When he recovers, he tells the physician that he usually takes medications for anxiety, bipolar disorder, and chronic low back pain. Temperature is 36.7 C (98.1 F), blood pressure is 129/82 mm Hg, pulse is 92/min, and respirations are 14/min. He appears anxious, tremulous, and diaphoretic. Withdrawal from which of the following medications is the most likely explanation for this patient's presentation?
Lorazepam - This patient's presentation is consistent with benzodiazepine withdrawal (eg, lorazepam), which is most often characterized by rebound anxiety, tremor, insomnia, and sympathetic hyperactivity (eg, diaphoresis, palpitations). In severe cases, psychotic symptoms (eg, hallucinations, delusions), seizures, and even death may occur. Risk of withdrawal is greatest with short-acting agents (eg, alprazolam), prolonged use, and use of higher doses. Benzodiazepines act on the GABAA receptor, enhancing the action of the natural ligand, GABA. The body adapts to chronic benzodiazepine exposure by downregulating the GABAA receptor, leading to tolerance, a phenomenon in which the same dose of a medication yields decreasing effects over time. This same adaptive downregulation process is responsible for the withdrawal syndrome when benzodiazepines are discontinued and the body is unable to balance opposing excitatory neurotransmitters. Benzodiazepine withdrawal is treated by starting a patient on a long-acting benzodiazepine (eg, diazepam) and planning for an extended, gradual taper.
A 26-year-old man is hospitalized after he was found in the park shouting and laughing to himself. He insists on wearing a cap lined with several layers of aluminum foil and explains that the hat prevents laser beams from reprogramming his mind. For the past 3 years, the patient has been hearing the voices of his deceased mother, the devil, and a world-famous singer. He has had one previous psychiatric hospitalization, during which he responded well to haloperidol. However, the patient stopped the medication shortly after discharge because he did not like the way it made him feel. A decision is made to administer a second-generation antipsychotic medication. Compared with first-generation antipsychotics, this class of medication is associated with which of the following?
Lower risk of acute dystonia - This patient is experiencing an acute psychotic episode (delusions, hallucinations, disorganized behavior) most likely due to schizophrenia, a chronic psychotic illness with typical onset in young adulthood. His treatment history indicates a good response to the first-generation antipsychotic (FGA) haloperidol but poor adherence, likely because of tolerability issues. As a class, FGAs are associated with a high risk of extrapyramidal symptoms (EPSs) due to their potent D2 antagonism. Types of EPS effects include acute dystonic reactions, drug-induced parkinsonism, akathisia (inner restlessness and inability to sit still), and tardive dyskinesia. Second-generation antipsychotics (SGAs) are often used for first-line treatment in schizophrenia due to their lower risk of EPSs compared with FGAs. However, SGAs are associated with weight gain and metabolic effects, including the development of diabetes. Side effect profiles of individual SGAs vary; olanzapine and clozapine are associated with the greatest risk of metabolic effects.
A 61-year-old man comes to the office due to tingling of his hands and feet. He has a history of diffuse large B cell lymphoma and has received several cycles of systemic chemotherapy with a regimen that includes cyclophosphamide, doxorubicin, and vincristine. Neurologic examination is notable for a symmetric distal neuropathy in a "stocking and glove" distribution. His electrolytes and fasting blood glucose are normal. The drug responsible for this patient's neurologic symptoms causes cell cycle arrest during which of the following stages?
M phase - This patient with diffuse large B cell lymphoma (most common type of non-Hodgkin lymphoma) has peripheral neuropathy likely due to vincristine. The vinca alkaloids (eg, vincristine, vinblastine) function by inhibiting microtubule formation. Specifically, these agents bind to β-tubulin, thereby preventing polymerization of microtubule proteins. This causes cell cycle-specific cytotoxicity during the M phase of the cell cycle as the replicated chromosomes are unable to align and subsequently unable to segregate into the daughter cells. Of the vinca alkaloids, vincristine is most classically associated with neurotoxicity, which is often dose-related and most commonly presents as peripheral neuropathy. Neurotoxicity likely results from disruption of neuronal microtubules, which are responsible for transporting organelles and other cellular products between the neuronal cell body and the axon terminals.
A 29-year-old woman is evaluated for severe left hip pain after twisting her leg. She has bony deformities of the lower extremities, and her mobility is limited. The patient has a history of hyperthyroidism, which was managed with radioiodine therapy. Menarche was at age 7, and she has regular 30-day cycles. Physical examination shows large, hyperpigmented macules with irregular borders located on the left shoulder, left side of the neck, and left buttock. X-ray findings are shown. Which of the following is the most likely diagnosis?
McCune-Albright syndrome - This patient's triad of fibrous dysplasia (multiple osteolytic-appearing lesions of the hip and pelvis), endocrine abnormalities, and café-au-lait spots suggests a diagnosis of McCune-Albright syndrome (MAS). Her x-ray reveals a pathological fracture through the left hip in the region of fibrous dysplasia. MAS results from a mosaic somatic mutation during embryogenesis in the GNAS gene encoding the stimulatory α subunit of G protein. This mutation causes constitutive activation of the G protein/cAMP/adenylate cyclase signaling cascade, which leads to a gain of function of the affected cells. Persistent G-protein stimulatory activity in melanocytes results in prominent café-au-lait macules (CALMs). CALMs, usually the first manifestation of MAS, are often large and unilateral with an irregular, "coast of Maine" border. In addition, autonomous endocrine function most commonly results in precocious puberty (onset of secondary sexual development before age 8 in girls). The mutation also results in increased proliferation of fibroblast-like cells, increased secretion of IL-6, and activation of osteoclasts (fibrous dysplasia). The term polyostotic refers to the presence of lesions in many bones, although they are typically unilateral.
A 37-year-old woman with a history of recurrent major depressive disorder comes to the office. Her father died last month after a long illness, and she is concerned that her depression is returning. The patient has little appetite, sleeps poorly, and has difficulty concentrating at her job as a teacher. She recently stopped going to the gym and socializing with friends, activities that she used to enjoy. She has been collecting pills from half-empty bottles of old medication and has considered taking all of them at once. The patient has no history of suicide attempts. Her mother completed suicide at age 40. Which of the following is the most important factor in assessing this patient's suicide risk?
Medication access - Assessment of suicide risk requires detailed questioning to determine the presence of suicidal thoughts and plans. Suicidal thoughts can be differentiated as passive (wish to be dead or not wake up) versus active suicidal ideation (actual thoughts of killing oneself). Patients who have active suicidal ideation should be further questioned about whether they have thought about specific methods of killing themselves and whether they have made any preparations and plans for suicide. Finally, the strength of the patient's intention to carry out the suicide plan should be assessed. Although this patient has several risk factors, it is her recent preparation for suicide (ie, collecting old medication with a plan of taking an overdose) that is the most concerning. Patients with active suicidal ideation and intent who have made preparations to carry out a specific method of suicide are at highest risk. Hospitalization may be necessary to ensure their safety.
A 34-year-old man comes to the clinic due to frequent clumsiness. For the last 6 months, he has had repeated minor injuries from walking into doorways and stationary objects. The patient was also reprimanded at work for causing his supervisor to spill coffee when he bumped into her in the hallway. Medical history is notable for recurrent renal stones; following a subsequent diagnostic evaluation, the patient underwent definitive treatment with neck surgery 3 years ago. Family history is unavailable as the patient was adopted. Physical examination reveals bitemporal visual field defects. Cranial nerves, motor strength, and deep-tendon reflexes are otherwise normal. In addition to brain imaging, this patient should also be screened for which of the following tumors?
Pancreatic - Multiple endocrine neoplasia type 1 (MEN1) is caused by mutations in the MEN1 tumor suppressor gene and is characterized by tumors of the parathyroid gland, pituitary, and pancreas (the "3 Ps"). Primary hyperparathyroidism is often the initial manifestation and usually presents with asymptomatic hypercalcemia or renal stones. Prolactin-secreting adenomas (prolactinomas) are the most common pituitary tumors. In premenopausal women, prolactinomas typically present with metabolic symptoms (eg, menstrual irregularities, galactorrhea); in men and postmenopausal women they usually present later when tumor enlargement leads to mass effect symptoms such as headache or bitemporal visual field defects (causing clumsiness in this patient) due to compression of the optic chiasm. Entero-pancreatic neuroendocrine tumors are the third major tumor type in MEN1. Gastrinoma (leading to Zollinger-Ellison syndrome) is the most common, followed by insulinoma and nonfunctional tumors. These tumors are often metastatic and are a frequent cause of tumor-related death in MEN1. This patient has visual field defects consistent with a pituitary mass lesion, which warrants cerebral imaging. In addition, he has a history of symptomatic hyperparathyroidism. Given these features of MEN1, he is also at increased risk for entero-pancreatic neuroendocrine tumors.
A 14-year-old previously healthy girl is evaluated for a 3-month history of low back pain. She is a member of her school gymnastics team, and the pain is worse after training sessions. The patient reports no significant back trauma and has had no weakness or numbness in the lower extremities. Menarche was at age 9 and she has had regular menstruations. Vital signs are within normal limits. Physical examination shows tenderness in the L5 region, but no neurologic deficits are present. A spine x-ray reveals anterior displacement of L5 vertebra relative to the S1 vertebra. This patient's condition is most likely caused by injury to which of the following structures?
Pars interarticularis - This adolescent athlete has spondylolisthesis (ie, anterior displacement of the vertebral body), which often occurs due to bilateral spondylolysis (ie, pars interarticularis fracture). The vertebral column is formed by stacked vertebra separated by cartilaginous discs held together by thick ligaments: The vertebral bodies form the anterior, weight-bearing portion of the vertebral column. The posterior portion of the vertebral column contains the midline spinous process, the transverse processes, and the articulating processes of the facet joints. The posterior vertebral arch connects the anterior and posterior portions of the vertebral column and consists of the pedicle, the intervening pars interarticularis, and the lamina. The posterior vertebral arch and the posterior portion of the vertebral body form the triangularly shaped spinal canal. Each vertebra has an anterior joint between the vertebral bodies separated by discs and a pair of facet joints posteriorly. Forward flexion of the spine stresses the anterior portion of the spine, including the vertebral bodies and discs; repetitive extension of the spine (as in gymnasts) stresses the facet joints and posterior vertebral arch, which can lead to spondylolysis with subsequent spondylolisthesis.
A 57-year-old man comes to the emergency department due to the abrupt onset of severe right eye pain and ipsilateral headache. The patient also has severe nausea and describes seeing halos around objects. After initial treatment with the appropriate medication, the pain severity decreases. Urine output also slightly increases, and the urine pH becomes more alkaline. The medication used to treat this patient's eye condition predominantly acts on which of the following nephron segments?
Proximal convoluted tubule - This patient with abrupt-onset unilateral headache and eye pain with nausea and visual halos likely has acute angle-closure glaucoma, which characterized by increased intraocular pressure caused by impaired drainage of aqueous humor. Aqueous humor production is promoted by carbonic anhydrase; carbonic anhydrase inhibitors (eg, acetazolamide) rapidly reduce intraocular pressure in patients with glaucoma. Carbonic anhydrase is also present in the renal proximal tubules, where it catalyzes reactions necessary for bicarbonate (HCO3) reabsorption. By inhibiting carbonic anhydrase, acetazolamide blocks reabsorption of HCO3− in the proximal tubule; the resulting urinary loss of HCO3− leads to mild diuresis with increased urine pH and consequent mild metabolic acidosis. Acetazolamide is often used to help offset the metabolic alkalosis that is commonly caused by loop diuretics.
A 34-year-old woman is being evaluated for fatigue and progressive exertional dyspnea. She goes mountain biking with friends a few times a month and recently noticed that she has to stop and rest more frequently when traveling uphill. The patient has no significant medical history and takes no medications. She occasionally drinks alcohol but does not use tobacco or illicit drugs. Her father died of a myocardial infarction at age 72. Lung auscultation is normal. An echocardiogram shows an enlarged coronary sinus. Which of the following is the most likely cause of the observed finding in this patient?
Pulmonary hypertension - Most of the venous drainage from the myocardium traverses the coronary sinus (CS), which delivers deoxygenated blood to the right atrium. The CS runs transversely in the left atrioventricular groove on the posterior aspect of the heart, and opens into the right atrium between the inferior vena cava and tricuspid valve at the CS orifice. Because the CS communicates freely with the right atrium, it will become dilated by any factor that causes dilation of the right atrium. The most common cause of coronary sinus dilation evident on echocardiography is elevated right-sided heart pressure secondary to pulmonary hypertension. CS dilation also occurs in patients with anomalous venous drainage into the CS, including persistent left superior vena cava and total anomalous pulmonary venous return.
A 67-year-old man comes to the office with right tibial pain that started 3 months ago and has increased in intensity over time. He also has had progressive hearing impairment for the last year. Physical examination reveals local tenderness and a lumpy protuberance over the right tibia. After extensive evaluation, the patient undergoes a bone biopsy. The pathologist identifies numerous multinucleated cells, some containing over 100 nuclei. Which of the following factors is essential for the differentiation of the cells described by the pathologist?
Receptor activator of nuclear factor kappa-B ligand - This patient has pain and deformity of the long bones with hearing loss (due to bony deformity of the skull); these are typical features of Paget's disease of bone. The initial abnormality in Paget's disease is excessive osteoclastic bone resorption followed by increased bone formation by osteoblasts; this results in high bone turnover in the affected areas. The new bone formation is disorganized, and pagetic bone lesions typically appear on imaging as thickened areas of mixed sclerosis and lucency. Osteoblasts are cells with a single nucleus that arise from mesenchymal stem cells found in the periosteum and bone marrow. In contrast, osteoclasts originate from the mononuclear phagocytic cell lineage and are ultimately formed when several precursor cells fuse to create a multinucleated mature cell. Osteoclasts in Paget's disease are typically very large and can have up to 100 nuclei (normal osteoclasts have 2-5). The 2 most important factors for osteoclastic differentiation, macrophage colony-stimulating factor (M-CSF) and receptor for activated nuclear factor kappa-B ligand (RANK-L), are produced by osteoblasts and bone marrow stromal cells. Osteoprotegerin (OPG) is a physiologic decoy receptor that decreases binding of RANK-L to RANK. Inhibition of RANK-L to RANK receptor interaction reduces the differentiation and survival of osteoclasts, resulting in decreased bone resorption and increased bone density. OPG loss-of-function mutations cause juvenile Paget's disease. A monoclonal antibody (denosumab) that inhibits the RANK/RANK-L interaction also leads to increased bone density and is commonly used for the treatment of osteoporosis.
An 8-month-old girl is brought to the emergency department due to fussiness. Symptoms began about 4 hours ago, and the patient has vomited several times. The parents state that the vomitus is dark green but nonbloody. The patient was born at term via spontaneous vaginal delivery after an uncomplicated pregnancy. She has no known medical conditions and normally consumes breast milk and pureed foods. Examination demonstrates abdominal distension. Abdominal imaging is shown in the exhibit. Surgical intervention is needed in this patient to prevent ischemia to structures supplied by which of the following?
Superior mesenteric artery - This patient with bilious (dark green) emesis has midgut malrotation, as evidenced by the upper gastrointestinal series (sequential x-rays obtained after ingestion of radiopaque contrast) revealing proximal small bowel loops on the right side of the abdomen. Normally, at 4-8 weeks gestation, the rapidly growing midgut physiologically herniates through the umbilical ring and rotates 90 degrees counterclockwise; the midgut then returns to the abdominal cavity and rotates an additional 180 degrees counterclockwise. This rotation allows for appropriate positioning of the bowel loops within the abdomen to create a wide mesenteric base that extends from the duodenojejunal flexure in the left upper quadrant to the cecum in the right lower quadrant. Incomplete rotation causes midgut malrotation. Pathologic anatomic findings include the following: The duodenojejunal flexure and jejunal loops lie on the right (instead of the left) side of the abdomen The partially rotated cecum still lies within the right side of the abdomen but in the mid to upper quadrants and is held in place by fibrous bands (Ladd bands) crossing the duodenum. This results in a narrow mesenteric base that is abnormally mobile. This mobility permits twisting around the superior mesenteric artery (SMA), or midgut volvulus, that can lead to life-threatening bowel ischemia and necrosis involving the intestinal segments that the SMA perfuses (ie, distal duodenum to proximal transverse colon). The most common presenting symptom is bilious emesis and management is prompt surgical correction.
A 58-year-old woman comes to the office with new-onset low back pain. The patient was helping her friend move yesterday and strained her back. She does not drink alcohol or use illicit substances. Medical history includes hypertension and major depressive disorder currently treated with captopril and citalopram. A short course of medication is prescribed, and the patient is asked to monitor for development of diaphoresis, restlessness, tremors, and diarrhea. The patient was most likely prescribed which of the following medications?
Tramadol - The symptom constellation of diaphoresis, restlessness, tremors, and diarrhea is characteristic of serotonin syndrome, a potentially dangerous condition that results from excess serotonergic activity in the CNS. This patient is currently taking the selective serotonin reuptake inhibitor (SSRI) citalopram and was likely prescribed tramadol, an opioid analgesic that also has serotonergic activity. Tramadol acts as a mu opioid receptor agonist and serotonin and norepinephrine reuptake inhibitor and, in combination with an SSRI, can potentially cause serotonin syndrome. Onset of serotonin syndrome typically occurs within the first 24 hours after a change in dose or initiation of a serotonergic medication, and typically presents with the classic triad of mental status changes, autonomic instability, and neuromuscular hyperactivity. In addition, stimulation of serotonin receptors in the gut commonly results in gastrointestinal symptoms (eg, diarrhea) and hyperactive bowel sounds. Patients taking SSRIs should be cautioned about the risk of serotonin syndrome when a medication with serotonergic activity is added. Tramadol (or other causative agent) should be discontinued promptly if serotonin syndrome occurs.
A 32-year-old man is hospitalized with multiple fractures and internal bleeding following a motor vehicle collision. He is successfully resuscitated and taken to the operating room for fixation of a left femoral fracture. The patient's condition remains stable postoperatively, and he is transferred to the surgical floor. Blood pressure is 118/68 mm Hg and pulse is 88/min. He develops oliguria on the second day of hospitalization. Renal biopsy findings are shown. If the kidney biopsy were repeated 1 month from now, which of the following would most likely be seen?
Tubular re-epithelization - This patient has ischemic acute tubular necrosis (ATN) as a result of hypotension from hemorrhage. The clinical course of ATN may be divided into the initiation, maintenance (oliguric), and recovery phases. The initiation phase corresponds with the original ischemic or toxic insult and lasts approximately 24-36 hours. During this phase, only a slight decrease in urine output is present as renal tubular cell damage begins. During the maintenance phase, tubular damage is fully established, resulting in oliguria, fluid overload, and electrolyte abnormalities (eg, hyperkalemia, metabolic acidosis). This phase usually lasts 1-2 weeks, during which the glomerular filtration rate remains well below normal with a corresponding rise in serum creatinine. Light microscopy shows tubular epithelial necrosis, sloughing of cells with denuded basement membranes, and casts containing degenerating cells and debris. The recovery phase is characterized by the re-epithelization of tubules. The glomerular filtration rate recovers relatively quickly as the tubules clear of casts and debris. However, the tubular cells recover more gradually, resulting in transient polyuria and loss of electrolytes due to impaired tubular resorption and decreased renal concentrating ability. The majority of patients eventually have complete restoration of renal function.
A 35-year-old man is evaluated for progressive fatigue and shortness of breath. Recently, he has noticed bilateral leg swelling and abdominal distension despite overall weight loss. He does not use tobacco, alcohol, or illicit drugs. Despite treatment, the patient dies several weeks later. Autopsy reveals significant endocardial thickening with dense fibrous deposits around the tricuspid and pulmonary valves as well as moderate pulmonary valve stenosis. The left-sided cardiac chambers and valves are normal. Measuring the levels of which of the following substances would have helped in diagnosing this patient?
Urinary 5-hydroxyindoleacetic acid - The autopsy findings - endocardial thickening and fibrosis of tricuspid and pulmonary valves - are characteristic of carcinoid heart disease. Carcinoids are well-differentiated neuroendocrine tumors found most commonly in the distal small intestine and proximal colon, with a strong propensity for metastasis to the liver. These tumors secrete several products (including histamine, serotonin, and vasoactive intestinal peptide) that are metabolized in the liver. In patients with liver metastasis, these hormones are released directly into the systemic circulation, leading to carcinoid syndrome. Carcinoid heart disease is caused by excessive secretion of serotonin, which stimulates fibroblast growth and fibrogenesis. Pathognomonic plaque-like deposits of fibrous tissue occur most commonly on the endocardium, leading to tricuspid regurgitation, pulmonic valvulopathy, and right-sided heart failure (eg, ascites, peripheral edema). Endocardial fibrosis and thickening are generally limited to the right heart as vasoactive products are inactivated distally by pulmonary vascular endothelial monoamine oxidase. 5-hydroxyindoleacetic acid (5-HIAA) is an end product of serotonin metabolism, and elevated 24-hour urinary 5-HIAA levels are helpful in diagnosing suspected carcinoid syndrome.
A 6-year-old boy is brought to your office for a routine check-up. His mother remarks that he often seems uninterested in playing with his peers and appears to "run out of breath quickly." His medical records reveal that he has missed several pediatric vaccinations and has been hospitalized twice, once with a "chest infection" and once with abdominal pain. The patient mentions to you that occasionally his "bones hurt." Which of the following protein changes most likely accounts for this patient's condition?
Valine substitute for glutamic acid - This patient is exhibiting signs and symptoms of sickle cell anemia. A point mutation in the 6th codon of the beta-globin gene, which causes the substitution of valine (hydrophobic) for glutamic acid (hydrophilic), is responsible. The incorporation of this abnormal beta-globin protein into hemoglobin results in the formation of hemoglobin S (HbS). HbS polymerizes at low oxygen tension, causing sickling and hemolysis of erythrocytes and resultant vascular occlusion. This patient's poor exercise tolerance and exertional dyspnea are due to anemia. His history of acute chest syndrome, abdominal pain, and bone pain are due to vaso-occlusive events in the lungs, spleen and bone, respectively.
