USMLE Step 1 Pathophysiology Block 7

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USMLE Step 1 Pathophysiology Block 7 - Quiz

This is a block of 46 questions of MCQ type with images in some questions. Choose the best answer for each question and get explanation at the end of exam when you submit. Time permitted is 1 hour.


Questions and Answers
  • 1. 

    A peripheral blood smear shows normocytic, normochromic red blood cells. The other cell types are morphologically normal but reduced in number as well. Bone marrow biopsy in this patient would most likely show which of the following patterns?

    • A.

      Hypocellular marrow filled with fat cells and fibrotic stroma

    • B.

      Hypercellular marrow with megaloblastic hematopoiesis

    • C.

      Hypergranular promyelocytes with multiple Auer rods

    • D.

      Hypercellular marrow filled with numerous blast forms

    Correct Answer
    A. Hypocellular marrow filled with fat cells and fibrotic stroma
    Explanation
    This patient most likely has aplastic anemia, given his pancytopenia, very low reticulocyte count, and lack of splenomegaly. The differential diagnosis for pancytopenia without splenomegaly includes: severe vitamin B12 and folic acid deficiency anemia, aleukemic leukemia, and myelodysplastic syndrome. Bone marrow examination can distinguish a myeloproliferative disease with increased bone marrow cellularity from aplastic anemia, where the bone marrow is markedly hypocellular.
    In aplastic anemia, bone marrow hematopoietic elements are replaced by fat cells and fibrous stroma. Bone marrow aspiration typically produces a "dry tap." The absence of splenomegaly is key in diagnosing aplastic anemia; a patient with pancytopenia and splenomegaly is very unlikely to have this condition.

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  • 2. 

    A 17-year-old Caucasian female newly diagnosed with iron-deficiency anemia mentions that her menstrual bleeding lasts 7-8 days. She also notes occasional gingival bleeding. Her platelet count is normal. Further evaluation reveals that her platelets aggregate normally in response to ADP but poorly with addition of ristocetin. This abnormality is caused by a deficiency of:                                         

    • A.

      Fibrinogen

    • B.

      GP llb-llla receptors

    • C.

      Von Willebrand factor

    • D.

      Thromboxane A2

    • E.

      Hageman's factor

    Correct Answer
    C. Von Willebrand factor
    Explanation
    Von Willebrand factor (vWF) is synthesized by endothelial cells and stored in endothelium and platelets. It binds GP Ib-IX receptors on the platelet membrane and mediates platelet aggregation and adhesion to subendothelial collagen. Von Willebrand factor also serves as a carrier for factor VIII. Deficiency of vWF causes both impaired platelet function and coagulation pathway abnormalities.

    1. Decreased platelet adhesion and aggregation cause mucocutaneous bleeding. Patients notice easy bruising, prolonged bleeding after minor trauma, and heavy menses. Laboratory work-up reveals a normal platelet count and increased bleeding time. The ristocetin aggregation test is used to measure vWF-dependent platelet aggregation. Ristocetin activates GP Ib-IX receptors on platelets and makes them available for vWF binding. When the vWF level is decreased, there is poor platelet aggregation in the presence of ristocetin.

    2. vWF serves as a carrier for factor VIII and prolongs its half-life. The half-life of factor VIII bound to vWF is 12 hours, while the half-life of free factor VIII is 2 hours. Decreased levels of vWF, therefore, lead to functional deficiency of factor VIII (also called antihemophilic factor). This causes prolonged bleeding after tooth extraction and other minor surgeries, as well as prolonged PTT.

    The definitive diagnosis of von Willebrand disease is made by measuring the levels of different fractions of vWF factor. Treatment includes desmopressin (DDAVP), which stimulates vWF release from endothelium. Blood products containing vWF are used in severe forms of von Willebrand disease.

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  • 3. 

    A 50-year-old is started on warfarin therapy for new-onset atrial fibrillation. Thirty-six hours later, he develops a painful lesion on his arm. The lesion is shown beow. Which of the following is the most likely cause of this lesion?

    • A.

      Vitamin K deficiency

    • B.

      Protein C deficiency

    • C.

      Anti thrombin III deficiency

    • D.

      Autoimmune phenomena

    • E.

      Allergic drug reaction

    Correct Answer
    B. Protein C deficiency
    Explanation
    This patient is being treated with warfarin as a prophylaxis against thromboembolism secondary to atrial fibrillation. The photo depicts warfarin-induced skin necrosis, which happens in patients with a protein C or S deficiency who are started on warfarin. Protein C is natural anticoagulant (as is protein S). Following the initiation of warfarin, a rapid drop in factor VII and protein C levels occurs. If a protein C deficiency is present, the transient procoagulant/anticoagulant imbalance is further exaggerated, causing a relative hypercoagulable state with thrombotic occlusion of the microvasculature and skin necrosis.
    Treatment of warfarin-induced skin necrosis includes discontinuing warfarin and administering fresh frozen plasma to replenish protein C content.

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  • 4. 

    A mother brings her 12-year-old son to his pediatrician for evaluation of easy bruising. Physical examination is notable only for the presence of multiple bruises. There is no lymphadenopathy or hepatosplenomegaly. Laboratory studies show: Complete blood count Hemoglobin                 8.2 g/L Platelet count               80,000/mm3 Leukocyte count           2,100/mm3 Bone marrow biopsy reveals the following:What is the most likely diagnosis?

    • A.

      Myelofibrosis

    • B.

      Hairy cell leukemia

    • C.

      Myelodysplasia syndrome

    • D.

      Aplastic anemia

    • E.

      Myelophthisic anemia

    Correct Answer
    D. Aplastic anemia
    Explanation
    This patient has pancytopenia. The bone marrow histology shown above is characteristic of aplastic anemia (AA). Bone marrow in AA is virtually devoid of hematopoietic elements; fat cells, fibrous stroma, and scattered clusters of lymphocytes and plasma cells replace the normal tissue. (For this reason, bone marrow aspiration typically turns up a "dry tap.") The patient's bruising tendency is due to deficient megakaryocyte production and a resultant low platelet count.

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  • 5. 

    A 56-year-old smoker with recurrent hemoptysis presents to your office complaining of headaches. Physical examination reveals facial swelling, conjunctival edema and dilated vessels of the neck and upper trunk. Heart sounds are clear. This patient's condition is most likely caused by:

    • A.

      Pericardial effusion

    • B.

      Mediastinal mass

    • C.

      Superior sulcus tumor

    • D.

      Pleural effusion

    • E.

      Autoimmune disease

    Correct Answer
    B. Mediastinal mass
    Explanation
    This patient's symptoms are consistent with impaired venous return from the upper body. The superior vena cava provides the venous drainage of head, neck, upper trunk and upper extremities. Compression of the superior vena cava causes a combination of symptoms called the superior vena cava syndrome.
    The superior vena cava is a 6-8 cm long vein that drains into the right atrium. It is located in the medial mediastinum and is surrounded by the sternum, trachea, right bronchus, aorta, and pulmonary artery. It is located in close proximity to the perihilar and paratracheal lymph nodes. This vein has thin walls and is easily compressed by mediastinal masses.
    Bronchogenic carcinoma is the most common cause of superior vena cava syndrome. Non-Hodgkin lymphomas are the second most common cause. Patients with SVC syndrome complain of dyspnea, cough, and swelling of the face, neck and upper extremities. Headaches, dizziness and visual disturbances may occur due to elevated intracranial pressure. Dilated collateral veins may be seen in the upper torso.

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  • 6. 

    A 48-year-old male who died in a motor vehicle accident is found to have a small fibrotic focus in the lower lobe of the right lung and a calcified lymph node in the right lung hilus. These autopsy findings are most consistent with which of the following?

    • A.

      Primary exposure to M. tuberculosis

    • B.

      Hematogenous dissemination of M tuberculosis

    • C.

      Secondary M. tuberculosis infection

    • D.

      Mycobacterial elimination from the body

    • E.

      Poor immunity against mycobacterial infection

    Correct Answer
    A. Primary exposure to M. tuberculosis
    Explanation
    The finding of a fibrotic focus in the lower lobe of a lung in conjunction with a calcified lymph node can occur in a variety of settings, with Mycobacterium tuberculosis infection one of the more likely. In M. tuberculosis infection, a lower lobe lung lesion (Ghon focus) accompanied by ipsilateral hilar adenopathy is described as a Ghon complex. The Ghon complex occurs during initial infection with M. tuberculosis.
    M. tuberculosis is passed from person to person through the transmission of aerosolized airway secretions. These droplets are of varying sizes; larger droplets make contact with the tracheal and bronchial epithelium and are typically removed by mucociliary motion, while smaller droplets are carried to the alveoli and can establish infection. Most droplets of infectious size carry approximately five organisms. Pulmonary tuberculosis infection is first established after the gravity-assisted entry of small, organism-laden droplets into the lower lung fields. The mycobacteria are phagocytosed by alveolar macrophages, and the sulfatide virulence factor expressed by M tuberculosis allows for intracellular bacterial proliferation. While nestled within these macrophages, M tuberculosis enters the lymphatic circulation. Eventually, it can seed organs throughout the body.
    The immune reaction to M. tuberculosis is TH1 cell-mediated, resulting in caseating necrosis where the organisms are present. The caseating granulomas consist of T lymphocytes, epithelioid activated macrophages, Langhans giant cells (with a horseshoe-shaped arrangement of nuclei), and proliferating fibroblasts that actively synthesize collagen. The net result of this response is a "walling off" of the organisms within a fibrous capsule. Although eliminated in 95% of cases, dormant M. tuberculosis bacilli are still present within the larger granulomas of many patients, able to later cause secondary tuberculosis during periods of immunosuppression.

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  • 7. 

    A 56-year-old African American female presents to the emergency room reporting a three day history of dysuria and back pain. On physical examination, she has a temperature of 39.2°C (102.6 F), a blood pressure of 70/40 mm Hg, a pulse of 130/min, and respirations of 26/min. She is confused and her skin is warm to the touch. Over the next few hours she becomes hypoxic. Which of the following lung findings is most likely to develop during her hospitalization?

    • A.

      Wedge-shaped areas of hemorrhagic necrosis

    • B.

      Fluid accumulation in the alveolar spaces

    • C.

      Atheromatous deposits in the pulmonary arteries

    • D.

      Thick mucous plugs in bronchi and bronchioles

    • E.

      Scattered non-caseating granulomas

    Correct Answer
    B. Fluid accumulation in the alveolar spaces
    Explanation
    This patient's presentation is consistent with a urinary tract infection that has progressed to pyelonephritis and warm septic shock. Sepsis and shock are two major risk factors for adult respiratory distress syndrome (ARDS). In 75% of cases, ARDS arises within 24 hours of the precipitating cause. 95% of cases arise within 72 hours. In ARDS, widespread injury to the pulmonary microvascular endothelium and/or the alveolar epithelium causes the alveolocapillary membrane to be leaky. In sepsis and/or shock, the pulmonary capillary endothelial injury results from endotoxin-induced release of injurious products from adherent leukocytes and/or ischemia-induced release of injurious cytokines. This endothelial injury causes pulmonary interstitial and intra-alveolar edema, inflammation, and alveolar hyaline membrane formation. In non-cardiogenic pulmonary edema, the pulmonary capillary wedge pressure remains within normal limits.

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  • 8. 

    A 32-year-old Caucasian male is hospitalized after sustaining multiple long bone fractures in a motor vehicle accident. He now develops shortness of breath, confusion, and petechiae to the upper chest. The patient dies despite resuscitation efforts. A section of his lung tissue is shown on the slide below.A stain giving a dense black reaction was used to demonstrate. What is the black stained material as described?

    • A.

      Fibrin

    • B.

      Surfactant

    • C.

      Fat

    • D.

      Iron

    • E.

      Platelets

    Correct Answer
    C. Fat
    Explanation
    The histologic section of this patient's lung shows fat globules trapped in and occluding pulmonary microvessels. These globules have been stained with osmium tetroxide, which imparts a black color to fat.
    This patient developed respiratory distress, a non-focal neurologic disturbance, and chest lesions consistent with thrombocytopenia after suffering multiple long bone fractures, all features of the fat embolism syndrome. The fat embolism syndrome is a condition affecting less than 10% of patients with severe skeletal injuries, and is characterized by pulmonary insufficiency, diffuse neurological impairment, thrombocytopenia, and anemia. Fat globules dislodged from bone marrow enter the marrow vascular sinusoids and then occlude pulmonary microvessels, impairing gas exchange. Microvascular occlusion in the cerebral white matter, brain stem, and spinal cord causes the neurologic manifestations.
    The pulmonary and CMS microvascular and parenchymal dysfunction may be promoted by:
    1. release of mediators from platelets which adhere to and coat the fat emboli (a phenomenon also resulting in thrombocytopenia), and
    2. systemic activation of lipoprotein lipase and intravascular release of toxic levels of oleic acid
    The anemia is thought to be due to increased RBC aggregation and destruction, as well as possible pulmonary hemorrhage.

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  • 9. 

    A 65-year-old male dies in the hospital of an overwhelming pulmonary infection. Autopsy shows a right lower lung lobe that is pale, firm and airless. Histologically, the alveoli are filled with exudate containing neutrophils, fibrin and some fragmented red blood cells. This patient died during which phase of his disease?

    • A.

      Congestion

    • B.

      Red hepatization

    • C.

      Gray hepatization

    • D.

      Resolution

    • E.

      Organization

    Correct Answer
    C. Gray hepatization
    Explanation
    Pneumonias can be classified as one of three morphologic variants. Patchy inflammation of a number of lobules is characteristic of bronchopneumonia. In interstitial pneumonia, the inflammatory infiltrate is confined to the alveolar walls. When the inflammatory process involves an entire lung lobe, it is a lobar pneumonia. The patient described in this vignette has a lobar pneumonia.
    Lobar pneumonia typically follows four stages:

    Stage: Congestion (first 24 hours)- Macro- the affected lobe is red, heavy and boggy- Micro- Vascular dilatation
    Alveolar Exudates contains mostly bacteria
    Stage: Red hepatization(days 2-3) )- Macro- Red, firm lobe (liver-like consistency) - Micro- Alveolar exudate contains
    erythrocytes, neutrophils, and fibrin
    Stage: Gray hepatization(days 4-6) )- Macro- Gray-brown firm lobe) - Micro- RBCs disintegrate,Alveolar exudate contains Neutrophils and fibrin
    Stage: Resolution)- Macro- Restoration of normal architecture) - Micro- Enzymatic digestion of the exudate

    A lung lobe that is pale and firm macroscopically suggests the gray hepatization phase. Microscopic examination of the exudates would show neutrophils, fibrin and fragmented RBCs.

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  • 10. 

    A 65-year-old male presents to your office with a non-healing ulcer on his right foot. His past medical history is significant for recurrent high blood glucose readings for the last several years, but the patient has failed to comply with appropriate treatment. Physical examination is significantfor bilateral symmetric decrease in vibration sensation over the feet and ankles. Which of the following is most likely to be associated with this patient's condition?

    • A.

      Pancreatic islet infiltration with leukocytes

    • B.

      Pancreatic islet amyloid deposition

    • C.

      Circulating anti-islet cell antibodies

    • D.

      Strong linkage with HLA class II gene makeup

    • E.

      Episodic ketoacidosis that requires insulin therapy

    Correct Answer
    B. Pancreatic islet amyloid deposition
    Explanation
    The patient described in this vignette has type 2 diabetes mellitus. Two cardinal defects involved in pathophysiology of type 2 diabetes mellitus are insulin resistance and defective insulin secretion. Although still very controversial, many researchers believe that insulin resistance is the primary abnormality in type 2 diabetes mellitus. Early in the pathogenesis of type 2 diabetes, glucose tolerance remains normal because of a compensatory increase in insulin secretion from beta cells. This compensatory insulin response from beta cell insulin ultimately fails, causing poor glucose tolerance. A number of genetic and acquired factors are implicated in the beta-cell dysregulation of type 2 diabetes. Islet associated polypeptide (amylin, IAPP) is one factor thought to be responsible for this beta cell dysfunction. IAPP is co-secreted with insulin from beta cells; IAPP is then deposited in islet cells. Deposits of islet amyloid polypeptide are universally seen in pancreatic islets of patients with type 2 diabetes mellitus. Islet associated polypeptide was originally thought to be the causative agent in beta cell apoptosis and defective insulin secretion. However, this theory has been seriously questioned by the normal glucose tolerance and normal insulin response of transgenic mice that over-express human IAPP.

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  • 11. 

    A 39-year-old Caucasian female presents to your office with a palpable nodularity in the right breast. Pathologically, the lesion is composed of ducts distended by pleomorphic cells with prominent central necrosis. The lesion does not extend beyond the ductal basal membrane. Which of the following is the most likely diagnosis in this patient?

    • A.

      Paget disease

    • B.

      Comedocarcinoma

    • C.

      Medullary carcinoma

    • D.

      Sclerosing adenosis

    • E.

      Mammary duct ectasia

    Correct Answer
    B. Comedocarcinoma
    Explanation
    The typical histological picture of comedocarcinoma (DCIS) is described. Ductal carcinoma in situ (DCIS) is a precancerous breast lesion characterized by a malignant clonal cell proliferation contained by the surrounding ductal basement membrane. The (basal) myoepithelial layer of the duct is preserved and uninvolved. Usually only a single ductal system appears to have DCIS. However, far more extensive DCIS lesions can occur, with widespread involvement of the breast parenchyma occasionally identified. In mammographically screened populations, DCIS now represents 15-30% of all carcinomas and 50% of mammogram-identified carcinomas.
    Classically, DCIS is divided into five different subtypes: comedocarcinoma, solid, cribriform, papillary, and micropapillary. Most cases have a mixture of patterns. Comedocarcinoma, as seen in this patient, is identified as solid sheets of pleomorphic, high-grade cells with central necrosis. Chronic inflammation and periductal concentric fibrosis are additional findings. As the malignant cell membranes become necrotic they calcify, allowing mammographic detection of mi crocalcifi cation clusters. If the comedocarcinoma is extensive, the lesion maybe palpable as a poorly defined nodule.

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  • 12. 

    A 40-year-old male is diagnosed with refractory peptic ulceration and diarrhea. Fasting gastrin levels are markedly elevated. You suspect a multi-organ disease and are worried about other associated conditions. This patient's family history should be most scrutinized for which of the following?

    • A.

      Multiple endocrine neoplasia type 1

    • B.

      Multiple endocrine neoplasia type 2 A

    • C.

      Multiple endocrine neoplasia type 2 B

    • D.

      Von Hippel-Lindau syndrome

    • E.

      Retinoblastoma and osteosarcoma

    Correct Answer
    A. Multiple endocrine neoplasia type 1
    Explanation
    Multiple Endocrine Neoplasia (MEN) refers to a group of familial disorders characterized by specific clusters of endocrine abnormalities. These aberrations result from hyperplasia or tumors of assorted endocrine organs. Although the various MEN syndromes do have similarities, there are unique features of each. MEN type 1 is characterized by hyperparathyroidism, pituitary tumors, and pancreatic tumors, although not all of these are present in every patient with MEN type I.
    MEN type 1 most commonly results in hyperparathyroidism, caused by parathyroid chief-cell hyperplasia, which results in hypercalcemia. Although, the most common presenting feature of MEN type 1 is hyperparathyroidism and hypercalcemia, large number of patients with MEN type 1 present with refactory peptic ulcer disease. About 70% of patients with MEN type I have endocrine pancreatic tumors—these tumors usually secrete gastrin, which causes refractory peptic ulceration (Zollinger-Ellison syndrome). Pancreatic tumors in MEN type 1 can also secrete other hormones—excess insulin manifests as hypoglycemia and excess vasoactive intestinal polypeptide manifests in massive diarrhea. A possible family history of multiple endocrine neoplasia should be sought in any patient who presents with Zollinger-Ellison syndrome.

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  • 13. 

    A 50-year-old male presents to the emergency room with a sudden severe headache, double vision, and bitemporal hemianopsia. He says that he's had decreased libido and mild headaches for a few months. As you are presenting to your attending, he develops cardiovascular collapse and dies, despite aggressive resuscitation. Autopsy will most likely reveal which of the following?

    • A.

      Rupture of berry aneurysm

    • B.

      Pituitary hemorrhage

    • C.

      Pulmonary embolism

    • D.

      Ischemic necrosis of pituitary

    • E.

      Acute congestive glaucoma

    Correct Answer
    B. Pituitary hemorrhage
    Explanation
    The patient described in the vignette most likely had pituitary apoplexy, which is acute bleeding in to a preexisting pituitary adenoma. Pituitary apoplexy is a medical emergency; without treatment, prognosis is poor. Symptoms will be bimodal; acute and chronic. The long-standing symptoms of a pituitary tumor will be present for months, as with this man's headache and decreased libido; accompanying these chronic symptoms will be an acute presentation, as with the severe headache and visual disturbances in this patient.
    Signs of meningeal irritation can also be seen in pituitary apoplexy, mimicking a subarachnoid hemorrhage. A careful physical exam can differentiate a subarachnoid hemorrhage from a sellar mass with suprasellar extension (pituitary tumor) by the presence of bitemporal hemianopsia, present only in the latter. Patients suffering from pituitary apoplexy develop cardiovascular collapse because ACTH deficiency leads to adrenocortical insufficiency. An urgent neurosurgical consultation and treatment with glucocorticoids are required.

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  • 14. 

    A 46-year-old female presents to your office with persistent diarrhea, weight loss and abdominal pain. Her diarrhea started several months ago and has not responded to antibiotics. The diarrhea does not remit with fasting. An upper gastrointestinal series revealed postbulbal duodenal and jejunal ulcers. Which of the following hormones is most likely to be elevated in this patient?

    • A.

      Gastrin

    • B.

      Insulin

    • C.

      Glucagon

    • D.

      VIP

    • E.

      Somatostatin

    Correct Answer
    A. Gastrin
    Explanation
    This patient has a clinical presentation highly suggestive of gastrinoma. Gastrinomas are neuroendocrine tumors that are most commonly located in the pancreas, the peri pancreatic tissue around the head of the pancreas, or the duodenum. The gastrin produced by these tumors stimulates gastric acid production, resulting in gastrointestinal ulcerations, oftentimes in unusual locations, such as the jejunum. In fact, the presence of jejunal ulcers is strongly suggestive of a diagnosis of gastrinoma. Patients with gastrinomas also often complain of diarrhea and abdominal pain.
    The diagnosis of gastrinoma is made by measuring basal and stimulated gastrin levels. Workup of all patients with newly diagnosed gastrinoma should include measurement of serum calcium, PTH, and pituitary hormones, because of the association with MEN-I. Proton pump inhibitors are the first-line therapy for most gastrinomas.

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  • 15. 

    A 34-year-old Caucasian female presents to your office complaining of mood swings, difficulty concentrating, and a hand tremor that started only recently. She also admits to having discomfort in her neck. The discomfort radiates to her ears, particularly on swallowing. She ignored the neck and ear discomfort at first because she thought they might be related to flu-like symptoms that she had few weeks ago. Her blood pressure is 140/80 mmHg, and heart rate is 105/min. You proceed with a thyroid scan which shows a diffuse decrease in radioactive iodine uptake. Erythrocyte sedimentation rate (ESR) is 105 mm/Hr. Which of the following pathological changes in the thyroid gland is most consistent with the clinical scenario described?

    • A.

      Follicular hyperplasia with tall cells forming intrafollicular papillary projections

    • B.

      Mononuclear, parenchymal infiltration with well-developed germinal centers

    • C.

      Mixed, cellular infiltration with occasional multinucleate giant cells

    • D.

      Extensive stromal fibrosis extending beyond the thyroid capsule

    • E.

      Branching papillary structures with interspersed calcified bodies

    Correct Answer
    C. Mixed, cellular infiltration with occasional multinucleate giant cells
    Explanation
    The clinical picture described in this vignette is indicative of subacute thyroiditis. Subacute granulomatous thyroiditis is also known as de Quervain's thyroiditis or granulomatous thyroiditis. It is possibly caused by a viral infection. The patient has had a recent illness, possibly viral, and also has various features of thyrotoxicosis, tenderness over the thyroid gland, increased ESR, and a markedly reduced radioactive iodine uptake. Thyrotoxicosis in subacute thryoiditis is caused by release of stored thyroid hormones secondary to thyroid inflammation; subacute thryoiditis does not cause excessive production of thyroid hormone, which is why iodine uptake is decreased.
    The involvement of thyroid gland in subacute thyroiditis can be patchy. Initial neutrophil infiltration predominance is followed by infiltration of lymphocytes, histiocytes, and multinucleated giant cells. The thyroid follicles become disrupted, and multinucleated giant cells surround the fragmented colloid. The thyrotoxic phase is followed by a hypothyroid phase for few months. Most patients eventually recover without any residual thyroid dysfunction. An antithyroid peroxidase antibody titer is not elevated in these patients. Most patients respond to non-steroidal antiinflammatory drugs for thyroid pain and inflammation.

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  • 16. 

    A 44-year-old Caucasian male comes to your office complaining of increased fatigability, trouble sleeping, and heart palpitations. He has lost ten pounds over the last three months. His past medical history is non-contributory. He admits that he is "under a lot of pressure" at his job, but can not think of any precipitating factors for his insomnia. Laboratory tests reveal a decreased serum TSH concentration. Which of the following would most likely indicate the cause of this patient's condition?

    • A.

      Atrial fibrillation

    • B.

      Tremor of the outstretched hands

    • C.

      Skin infiltration of the lower legs

    • D.

      Increased serum alkaline phosphatase

    • E.

      Heat intolerance

    Correct Answer
    C. Skin infiltration of the lower legs
    Explanation
    Any of the answer choices could be true in a patient with hyperthyroidism. The key is to determine which answer is specific to a particular thyroid disease. Extra-thyroidal manifestations, including infiltrative ophthalmopathy and pretibial myxedema, are specific to Graves' disease. It should be noted that "myxedema" is a very confusing term: "pretibial myxedema" describes a diffuse, non-pitting edema and thickening of the skin, usually present over the tibia, associated primarily with Graves' disease; however, the term "myxedema" describes the overall disease process of hypothyroidism. Exophthalmos and pretibial myxedema are not seen with other causes of hyperthyroidism, such as a toxic multinodular goiter or a toxic thyroid nodule.

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  • 17. 

    A 40-year-old female who has been having episodic headaches is admitted to a local hospital for hypertensive emergency. Evaluation shows increased urinary metanephrines. Hyperactivity of which of the following structures is most likely responsible for this patient's symptoms?

    • A.

      Chromaffin cells of the adrenal medulla

    • B.

      Zona glomerulosa of the adrenals

    • C.

      Zonafasciculata of the adrenals

    • D.

      Zona reticulata of the adrenals

    • E.

      Juxtaglomerular cells of the kidney

    Correct Answer
    A. Chromaffin cells of the adrenal medulla
    Explanation
    Pheochromocytoma is a tumor of the chromaffin tissue of the adrenal medulla that causes increased production of catecholamines (norepinephrine and epinephrine), resulting in increased vascular tone and hypertension. Other features of catecholamine excess include: headache, diaphoresis, anxiety, palpitations, chest pain, and orthostatic hypotension (due to low plasma volume). For reasons not completely understood, these symptoms are typically episodic.
    The 'Rule of 10s' is helpful in remembering the features of pheochromocytoma. Roughly 10% of pheochromocytomas occur as part of hereditary syndromes (e.g. MEN 2 A and B, von Hippel Lindau disease), 10% of pheochromocytomas are bilateral, and 10% are extra-adrenal. Only 10% of pheochromocytomas are malignant; the

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  • 18. 

    A neonate who weighs 4.5 kg (9 lb, 15 oz.) is found to be hypoglycemic. His mother was treated with insulin during the pregnancy after being diagnosed with gestational diabetes The mother has a history of depression and drug abuse in the past, but she denies "using" for the past few years. VV&ich of the following is the most likely cause of this neonate's hypoglycemia?

    • A.

      Placental transfer of insulin

    • B.

      Diffuse hyperplasia of the islets

    • C.

      Hypothyroidism

    • D.

      Glycogen storage disease

    • E.

      IGF-2 producing fibrosarcoma

    Correct Answer
    B. Diffuse hyperplasia of the islets
    Explanation
    Poor glucose control during pregnancy is associated with number of birth defects. Macrosomia is the classic "defect'' —this term describes a large infant (larger than 4.0 kg by conservative measures). If blood glucose is poorly controlled with diet and activity, insulin treatment is generally started. High glucose levels in the mother enter fetal circulation, causing high blood glucose levels to be present in the fetus. The fetus responds to this elevated blood glucose by increasing insulin. Obviously, the amount of insulin generated by these fetuses is more than normal, and beta cell hyperplasia results. Once free from the mother, the neonate continues to over-produce insulin (hyperinsulinemia), which can cause the neonate to experience severe hypoglycemia. High insulin levels are also responsible for the increased fat deposition and enhanced fetal growth that results in macrosomia.

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  • 19. 

    A 32-year-old Caucasian male comes to your office complaining of visual problems. He has had several "near-misses" in his car lately, being nearly hit by cars coming from both the right and the left. He also admits to having headaches that respond to acetaminophen. Which of the following hormones is most likely elevated in this patient?

    • A.

      Growth hormone

    • B.

      Adrenocortical-stimulating hormone

    • C.

      Thyroid-stimulating hormone

    • D.

      Prolactin

    • E.

      Follicle-stimulating hormone

    Correct Answer
    D. Prolactin
    Explanation
    This patient's symptoms should immediately make you suspect a pituitary tumor-he has a headache accompanied by loss of peripheral vision. Compression of the optic chiasm by suprasellar extension of pituitary tumors causes the characteristic bitemporal hemianopsia. His headache is likely caused by an increase in intracranial pressure, caused by mass effect of the tumor.
    Pituitary tumors typically arise from one of the five major cell types of the anterior pituitary gland. Approximately 60% of pituitary tumors are prolactin-secreting adenomas. Prolactin is a 199 amino acid peptide hormone secreted from lactotrophs of the pituitary gland. The primary physiologic action of prolactin is preparation of the breasts for milk production/lactation in the postpartum period. Prolactinomas stimulate inappropriate milk production in nonpostpartum females (galactorrhea). Prolactin also suppresses gonadotrophin-releasing hormone (GnRH) production from the hypothalamus, which causes decreased libido, amenorrhea, and infertility. Pituitary tumors can grow beyond the limits of the sella turcica, causing compression and erosion of surrounding structures. If the pituitary tumor grows superiorly, it erodes the optic chiasm; laterally, it invades the cavernous sinus; inferiorly, it grows into the sphenoid sinus. A growing pituitary tumor can also compress normal pituitary cells, causing hypopituitarism.

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  • 20. 

    A 55-year-old African-American male is found to have abnormal serum chemistries during routine laboratory testing. His only other medical problem is hypertension, for which he is being treated with pharmacologic therapy, accompanied by weight reduction and low salt intake. His lab studies are as follows: Chemistry panel Serum sodium 134 mEq/L Serum potassium 3.8 mEq/L Blood urea nitrogen (BUN) 18 mg/dL Serum creatinine 0.8 mg/dL Calcium 11.0 mg/dL Blood glucose 98 mg/dL Parathyroid hormone decreased Which of the following is the most likely cause of his symptoms?

    • A.

      Primary hyperparathyroidism

    • B.

      Medication

    • C.

      Hypothyroidism

    • D.

      Secondary hyperparathyroidism

    • E.

      Familial hypocalciuric hypercalcemia

    Correct Answer
    B. Medication
    Explanation
    Hydrochlorothiazide (HCTZ) is one of the commonest agents used for the treatment of hypertension. Unfortunately, HCTZ has some adverse effects. For instance, HCTZ causes an increase in the distal tubular reabsorption of calcium, causing both relative hypercalcemia as well as hypocalciuria. The increased serum calcium levels seen with HCTZ therapy usually suppress PTH.

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