A 6-year-old child presents for evaluation of a medical condition associated with recurrent infections. After reviewing all of the medical history, gene therapy is offered to treat a deficiency in adenosine deaminase (ADA). ADA deficiency is the most common autosomal recessive mutation in which of the following diseases?
Q142
A 49-year-old woman with a history of intravenous drug use comes to the physician because of a 6-month history of fatigue, joint pain, and episodic, painful discoloration in her fingers when exposed to cold weather. She takes no medications. She has smoked one pack of cigarettes daily for the past 22 years. She appears tired. Physical examination shows palpable, nonblanching purpura over the hands and feet. Neurological examination shows weakness and decreased sensation in all extremities. Serum studies show:
Alanine aminotransferase 78 U/L
Aspartate aminotransferase 90 U/L
Urea nitrogen 18 mg/dL
Creatinine 1.5 mg/dL
Which of the following processes is the most likely explanation for this patient's current condition?
Q143
A 52-year-old woman presents with erosions in her mouth that are persistent and painful. She says that symptoms appeared gradually 1 week ago and have progressively worsened. She also notes that, several days ago, flaccid blisters appeared on her skin, which almost immediately transformed to erosions as well. Which of the following is the most likely diagnosis?
Q144
A 24-year-old man comes to the emergency department because of progressive shortness of breath and intermittent cough with blood-tinged sputum for the past 10 days. During this time, he had three episodes of blood in his urine. Six years ago, he was diagnosed with latent tuberculosis after a positive routine tuberculin skin test, and he was treated accordingly. His maternal aunt has systemic lupus erythematosus. The patient does not take any medications. His temperature is 37°C (98.6°F), pulse is 92/min, respirations are 28/min, and blood pressure is 152/90 mm Hg. Diffuse crackles are heard at both lung bases. Laboratory studies show:
Serum
Urea nitrogen 32 mg/dL
Creatinine 3.5 mg/dL
Urine
Protein 2+
Blood 3+
RBC casts numerous
WBC casts negative
A chest x-ray shows patchy, pulmonary infiltrates bilaterally. A renal biopsy in this patient shows linear deposits of IgG along the glomerular basement membrane. Which of the following is the most likely diagnosis?
Q145
A 1-year-old infant is brought to the emergency department by his parents because of fever and rapid breathing for the past 2 days. He had a mild seizure on the way to the emergency department and developed altered sensorium. His mother states that the patient has had recurrent respiratory infections since birth. He was delivered vaginally at term and without complications. He is up to date on his vaccines and has met all developmental milestones. His temperature is 37.0°C (98.6°F), pulse rate is 200/min, and respirations are 50/min. He is lethargic, irritable, and crying excessively. Physical examination is notable for a small head, an elongated face, broad nose, low set ears, and cleft palate. Cardiopulmonary exam is remarkable for a parasternal thrill, grade IV pansystolic murmur, and crackles over both lung bases. Laboratory studies show hypocalcemia and lymphopenia. Blood cultures are drawn and broad-spectrum antibiotics are started, and the child is admitted to the pediatric intensive care unit. The intensivist suspects a genetic abnormality and a fluorescence in situ hybridization (FISH) analysis is ordered which shows 22q11.2 deletion. Despite maximal therapy, the infant succumbs to his illness. The parents of the child request an autopsy. Which of the following findings is the most likely to be present on autopsy?
Q146
A 48-year-old man comes to the emergency department because of a 2-hour history of severe left-sided colicky flank pain that radiates towards his groin. He has vomited twice. Last year, he was treated with ibuprofen for swelling and pain of his left toe. He drinks 4-5 beers most days of the week. Examination shows left costovertebral angle tenderness. An upright x-ray of the abdomen shows no abnormalities. A CT scan of the abdomen and pelvis shows an 9-mm stone in the proximal ureter on the left. Which of the following is most likely to be seen on urinalysis?
Q147
A 7-year-old girl is brought to the physician by her mother because of a 5-day history of fever, fatigue, and red spots on her body. Her temperature is 38.3°C (101.1°F), pulse is 115/min, and blood pressure is 100/60 mm Hg. Physical examination shows pallor and petechiae over the trunk and lower extremities. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Peripheral blood smear shows normochromic, normocytic cells. A bone marrow aspirate shows hypocellularity. Which of the following is the most likely cause of this patient's findings?
Q148
A 25-year-old woman comes to the physician because of a 2-week history of episodic bleeding from the nose and gums and one episode of blood in her urine. She was treated with chloramphenicol 1 month ago for Rickettsia rickettsii infection. Her pulse is 130/min, respirations are 22/min, and blood pressure is 105/70 mm Hg. Examination shows mucosal pallor, scattered petechiae, and ecchymoses on the extremities. Laboratory studies show:
Hemoglobin 6.3 g/dL
Hematocrit 26%
Leukocyte count 900/mm3 (30% neutrophils)
Platelet count 50,000/mm3
The physician recommends a blood transfusion and informs her of the risks and benefits. Which of the following red blood cell preparations will most significantly reduce the risk of transfusion-related cytomegalovirus infection?
Q149
A 73-year-old man comes to the physician because of progressive fatigue and shortness of breath on exertion for 3 weeks. He has swelling of his legs. He has not had nausea or vomiting. His symptoms began shortly after he returned from a trip to Cambodia. He occasionally takes ibuprofen for chronic back pain. He has a history of arterial hypertension and osteoarthritis of both knees. He had an episode of pneumonia 4 months ago. His current medications include lisinopril and hydrochlorothiazide. He has no history of drinking or smoking. His temperature is 37°C (98.6°F), pulse is 101/min, and blood pressure is 135/76 mm Hg. Examination shows pitting edema of the upper and lower extremities. Laboratory studies show:
Hemoglobin 14.1 g/dL
Leukocyte count 6,800/mm3
Platelet count 216,000/mm3
Serum
Urea nitrogen 26 mg/dL
Creatinine 2.9 mg/dL
Albumin 1.6 g/dL
Urine
Blood negative
Protein 4+
Glucose negative
Renal biopsy with Congo red stain shows apple-green birefringence under polarized light. Further evaluation of this patient is most likely to show which of the following findings?
Q150
A 23-year-old African American man presents to the emergency department with severe pain. The patient, who is a construction worker, was at work when he suddenly experienced severe pain in his arms, legs, chest, and back. He has experienced this before and was treated 2 months ago for a similar concern. His temperature is 100°F (37.8°C), blood pressure is 127/68 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for tenderness to palpation of the patient's legs, chest, abdomen, and arms. Laboratory values are obtained and shown below.
Hemoglobin: 10 g/dL
Hematocrit: 30%
Leukocyte count: 8,500/mm³ with normal differential
Platelet count: 199,000/mm³
Reticulocyte count: 8%
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.9 mEq/L
HCO3-: 25 mEq/L
BUN: 23 mg/dL
LDH: 327 U/L
Glucose: 99 mg/dL
Creatinine: 1.1 mg/dL
Ca2+: 10.2 mg/dL
AST: 12 U/L
ALT: 10 U/L
Which of the following is the most likely diagnosis?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 141: A 6-year-old child presents for evaluation of a medical condition associated with recurrent infections. After reviewing all of the medical history, gene therapy is offered to treat a deficiency in adenosine deaminase (ADA). ADA deficiency is the most common autosomal recessive mutation in which of the following diseases?
A. Wiskott-Aldrich Syndrome
B. Bruton's Agammaglobulinemia
C. Severe Combined Immunodeficiency (Correct Answer)
D. DiGeorge Syndrome
E. Hyper-IgM Syndrome
Explanation: ***Severe Combined Immunodeficiency***
- **Adenosine deaminase (ADA) deficiency** leads to the accumulation of toxic metabolites that impair lymphocyte development and function, primarily affecting **T and B cells**, which is a common cause of SCID.
- Patients with SCID present with **recurrent, severe infections** due to profound immunodeficiency, making them candidates for treatments like gene therapy.
*Wiskott-Aldrich Syndrome*
- This is an **X-linked recessive disorder** characterized by eczema, thrombocytopenia, and immunodeficiency, but it is caused by a mutation in the **WASP gene**, not ADA deficiency.
- While it involves immunodeficiency and recurrent infections, the underlying genetic defect and specific clinical triad are distinct from ADA deficiency.
*Bruton's Agammaglobulinemia*
- This is an **X-linked recessive disorder** caused by a defect in the **BTK gene**, leading to a lack of mature B cells and hence very low levels of immunoglobulins.
- While it results in recurrent bacterial infections due to absent antibodies, its genetic cause and primary immunological defect (B cell specific) differ from ADA deficiency.
*DiGeorge Syndrome*
- This is a developmental disorder caused by a **microdeletion on chromosome 22q11.2**, leading to abnormal development of the third and fourth pharyngeal pouches.
- It results in **T-cell deficiency** due to thymic aplasia/hypoplasia, hypocalcemia due to parathyroid hypoplasia, and congenital heart defects, but not ADA deficiency.
*Hyper-IgM Syndrome*
- This syndrome is characterized by normal or elevated IgM levels and deficiencies in other immunoglobulins (IgG, IgA, IgE), largely due to defects in **CD40-CD40L interaction** or other genes involved in isotype switching.
- Patients suffer from recurrent infections and opportunistic infections but the genetic basis and specific immunological defect are distinct from ADA deficiency.
Question 142: A 49-year-old woman with a history of intravenous drug use comes to the physician because of a 6-month history of fatigue, joint pain, and episodic, painful discoloration in her fingers when exposed to cold weather. She takes no medications. She has smoked one pack of cigarettes daily for the past 22 years. She appears tired. Physical examination shows palpable, nonblanching purpura over the hands and feet. Neurological examination shows weakness and decreased sensation in all extremities. Serum studies show:
Alanine aminotransferase 78 U/L
Aspartate aminotransferase 90 U/L
Urea nitrogen 18 mg/dL
Creatinine 1.5 mg/dL
Which of the following processes is the most likely explanation for this patient's current condition?
A. Fibroblast proliferation
B. Immune complex formation (Correct Answer)
C. Spirochete infection
D. Tobacco hypersensitivity
E. Plasma cell malignancy
Explanation: **Immune complex formation**
* The patient's history of **intravenous drug use** and a constellation of symptoms including **fatigue**, **joint pain**, **Raynaud phenomena**, and **palpable purpura** are highly suggestive of **mixed cryoglobulinemia**.
* **Mixed cryoglobulinemia** is characterized by the presence of **immune complexes** (immunoglobulins that precipitate in the cold) that can deposit in small and medium-sized vessels, leading to **vasculitis** and organ damage, often triggered by chronic infections like **Hepatitis C** (common in IV drug users).
*Fibroblast proliferation*
* While **fibroblast proliferation** is involved in fibrosis and scaring, it does not explain the widespread systemic symptoms such as **purpura**, **neuropathy**, and **renal involvement** seen here.
* Conditions driven primarily by fibroblast proliferation, such as **scleroderma**, present with skin thickening and organ fibrosis but typically lack prominent vasculitic features like palpable purpura.
*Spirochete infection*
* **Spirochete infections** (e.g., syphilis, Lyme disease) can cause fatigue and joint pain, but they do not typically present with **palpable purpura**, **Raynaud phenomenon**, or the specific pattern of organ involvement (liver and kidney dysfunction) seen in this patient.
* While syphilis can cause central nervous system issues, the **peripheral neuropathy** described here along with cutaneous vasculitis does not align with a typical spirochetal presentation.
*Tobacco hypersensitivity*
* **Tobacco hypersensitivity** is not a recognized medical condition explaining this array of symptoms.
* Smoking is a risk factor for various vascular diseases (e.g., Buerger's disease), but it does not cause **immune-complex mediated vasculitis** with palpable purpura and neuropathy.
*Plasma cell malignancy*
* **Plasma cell malignancies** like **multiple myeloma** can cause fatigue, kidney problems, and neuropathy due to monoclonal immunoglobulin deposition or amyloidosis.
* However, **palpable purpura** and **Raynaud phenomena** are very uncommon primary manifestations of plasma cell malignancies, making immune complex vasculitis a more fitting diagnosis for this patient's presentation.
Question 143: A 52-year-old woman presents with erosions in her mouth that are persistent and painful. She says that symptoms appeared gradually 1 week ago and have progressively worsened. She also notes that, several days ago, flaccid blisters appeared on her skin, which almost immediately transformed to erosions as well. Which of the following is the most likely diagnosis?
A. Molluscum contagiosum
B. Psoriasis
C. Pemphigus vulgaris (Correct Answer)
D. Bullous pemphigoid
E. Staphylococcal infection (scalded skin syndrome)
Explanation: **Pemphigus vulgaris**
- The presence of **persistent and painful oral erosions** followed by **flaccid blisters** that quickly break into erosions on the skin is highly characteristic of pemphigus vulgaris. This is due to **acantholysis** (loss of cell-to-cell adhesion) within the epidermis.
- The oral lesions typically precede skin lesions and are often the first symptom, as seen in this patient, and are very painful.
*Molluscum contagiosum*
- Causes **dome-shaped, umbilicated papules** and does not present with widespread flaccid blisters or painful erosions.
- It is a viral infection common in children and immunocompromised individuals.
*Psoriasis*
- Characterized by **erythematous plaques with silvery scales**, typically found on extensor surfaces.
- It does not involve flaccid blisters or widespread mucosal erosions.
*Bullous pemphigoid*
- Presents with **tense bullae** on an erythematous or urticarial base, which are less likely to rupture quickly compared to the flaccid blisters of pemphigus vulgaris. Oral lesions are less common (affecting 10-30%) and generally less severe than in pemphigus vulgaris.
- It involves autoantibodies against **hemidesmosomes**, leading to subepidermal blistering.
*Staphylococcal infection (scalded skin syndrome)*
- Primarily affects infants and young children, causing widespread **erythema and superficial blistering**, resembling a burn, leading to epidermal sloughing.
- It can cause diffuse nonscarring exfoliation and not well-demarcated oral erosions or flaccid blisters leading to erosions in this age group as is seen in this patient.
Question 144: A 24-year-old man comes to the emergency department because of progressive shortness of breath and intermittent cough with blood-tinged sputum for the past 10 days. During this time, he had three episodes of blood in his urine. Six years ago, he was diagnosed with latent tuberculosis after a positive routine tuberculin skin test, and he was treated accordingly. His maternal aunt has systemic lupus erythematosus. The patient does not take any medications. His temperature is 37°C (98.6°F), pulse is 92/min, respirations are 28/min, and blood pressure is 152/90 mm Hg. Diffuse crackles are heard at both lung bases. Laboratory studies show:
Serum
Urea nitrogen 32 mg/dL
Creatinine 3.5 mg/dL
Urine
Protein 2+
Blood 3+
RBC casts numerous
WBC casts negative
A chest x-ray shows patchy, pulmonary infiltrates bilaterally. A renal biopsy in this patient shows linear deposits of IgG along the glomerular basement membrane. Which of the following is the most likely diagnosis?
A. Goodpasture syndrome (Correct Answer)
B. Lupus nephritis
C. Granulomatosis with polyangiitis
D. Reactivated tuberculosis
E. Microscopic polyangiitis
Explanation: **Goodpasture syndrome**
- The patient presents with **pulmonary hemorrhage** (shortness of breath, blood-tinged sputum, diffuse crackles, patchy infiltrates) and **rapidly progressive glomerulonephritis** (elevated creatinine, proteinuria, hematuria, RBC casts), which is characteristic of **Goodpasture syndrome**.
- The renal biopsy finding of **linear deposits of IgG along the glomerular basement membrane** is pathognomonic for Goodpasture syndrome, indicating the presence of anti-GBM antibodies.
*Lupus nephritis*
- While **systemic lupus erythematosus** can cause glomerulonephritis, the biopsy would show **granular immune complex deposits** (Class III, IV, or V lupus nephritis), not linear IgG deposits.
- Pulmonary involvement in lupus can occur but does not typically present as diffuse alveolar hemorrhage with linear IgG deposits.
*Granulomatosis with polyangiitis*
- This condition is characterized by **granulomatous inflammation** and **necrotizing vasculitis** affecting the respiratory tract and kidneys, often with c-ANCA positivity.
- However, the renal biopsy in granulomatosis with polyangiitis would typically show **pauci-immune glomerulonephritis** (i.e., minimal or no immune deposits), which contradicts the linear IgG deposits found.
*Reactivated tuberculosis*
- Although the patient has a history of latent tuberculosis, his current symptoms of **severe kidney failure** and **diffuse alveolar hemorrhage** are not typical presentations of reactivated pulmonary tuberculosis.
- Reactivated TB would be more likely to cause cavitation, chronic cough, and constitutional symptoms, not rapidly progressive glomerulonephritis with linear IgG deposition.
*Microscopic polyangiitis*
- Like granulomatosis with polyangiitis, microscopic polyangiitis is a **pauci-immune vasculitis** affecting small vessels and can cause lung and kidney involvement, often associated with p-ANCA.
- The key differentiating factor is the absence of immune complex or linear IgG deposition on renal biopsy in microscopic polyangiitis, which is inconsistent with the patient's findings.
Question 145: A 1-year-old infant is brought to the emergency department by his parents because of fever and rapid breathing for the past 2 days. He had a mild seizure on the way to the emergency department and developed altered sensorium. His mother states that the patient has had recurrent respiratory infections since birth. He was delivered vaginally at term and without complications. He is up to date on his vaccines and has met all developmental milestones. His temperature is 37.0°C (98.6°F), pulse rate is 200/min, and respirations are 50/min. He is lethargic, irritable, and crying excessively. Physical examination is notable for a small head, an elongated face, broad nose, low set ears, and cleft palate. Cardiopulmonary exam is remarkable for a parasternal thrill, grade IV pansystolic murmur, and crackles over both lung bases. Laboratory studies show hypocalcemia and lymphopenia. Blood cultures are drawn and broad-spectrum antibiotics are started, and the child is admitted to the pediatric intensive care unit. The intensivist suspects a genetic abnormality and a fluorescence in situ hybridization (FISH) analysis is ordered which shows 22q11.2 deletion. Despite maximal therapy, the infant succumbs to his illness. The parents of the child request an autopsy. Which of the following findings is the most likely to be present on autopsy?
A. Aplastic thymus (Correct Answer)
B. Hypercellular bone marrow
C. Accessory spleen
D. Hypertrophy of Hassall's corpuscles
E. Absent follicles in the lymph nodes
Explanation: ***Aplastic thymus***
- This infant's presentation with 22q11.2 deletion, recurrent respiratory infections, hypocalcemia, and congenital heart disease (parasternal thrill, pansystolic murmur) is classic for **DiGeorge syndrome**.
- **DiGeorge syndrome** is characterized by thymic aplasia or hypoplasia, leading to **T-cell immunodeficiency**, and parathyroid hypoplasia, resulting in **hypocalcemia**.
*Hypercellular bone marrow*
- **Hypercellular bone marrow** indicates increased hematopoietic activity and is not a characteristic finding in DiGeorge syndrome.
- In immunodeficiency states like DiGeorge, the bone marrow itself is often normal or may show lymphoid depletion.
*Accessory spleen*
- **Accessory spleen** is a common congenital anomaly and is not specifically associated with DiGeorge syndrome or its immunodeficiency.
- While it can occur in individuals with DiGeorge syndrome, it is not a direct pathological consequence of the 22q11.2 deletion.
*Hypertrophy of Hassall's corpuscles*
- **Hassall's corpuscles** are found in the medulla of the thymus, and their hypertrophy would indicate an active or hyperplastic thymus, which is contrary to the **thymic aplasia/hypoplasia** seen in DiGeorge syndrome.
- In DiGeorge syndrome, the thymus is either absent or severely underdeveloped.
*Absent follicles in the lymph nodes*
- **Absent follicles in the lymph nodes** would indicate a B-cell deficiency, as follicles are primarily composed of B lymphocytes.
- DiGeorge syndrome primarily affects **T-cell development** due to thymic abnormalities, not B-cell development or lymph node follicular formation directly.
Question 146: A 48-year-old man comes to the emergency department because of a 2-hour history of severe left-sided colicky flank pain that radiates towards his groin. He has vomited twice. Last year, he was treated with ibuprofen for swelling and pain of his left toe. He drinks 4-5 beers most days of the week. Examination shows left costovertebral angle tenderness. An upright x-ray of the abdomen shows no abnormalities. A CT scan of the abdomen and pelvis shows an 9-mm stone in the proximal ureter on the left. Which of the following is most likely to be seen on urinalysis?
A. Rhomboid-shaped crystals
B. Coffin-lid-like crystals
C. Red blood cell casts
D. Wedge-shaped crystals (Correct Answer)
E. Hexagon-shaped crystals
Explanation: ***Wedge-shaped crystals***
- The patient's history of **left toe swelling and pain** (suggestive of **gout**) and **alcohol consumption** strongly indicate **hyperuricemia** and predisposition to **uric acid stone** formation.
- **Uric acid stones are radiolucent**, which explains why the **X-ray showed no abnormalities** despite a 9-mm stone being visible on CT scan—this is a classic presentation.
- **Uric acid crystals** appear as **wedge-shaped, rhomboid, or pleomorphic** yellow-brown crystals in **acidic urine** (pH <5.5).
- This is the most likely finding on urinalysis given the clinical context.
*Rhomboid-shaped crystals*
- **Rhomboid-shaped crystals** are also characteristic of **uric acid**, making this another acceptable description of the same crystal type.
- Both "wedge-shaped" and "rhomboid" refer to **uric acid crystals**; however, "wedge-shaped" is the more commonly used descriptor in clinical practice.
- If this were an option and wedge-shaped were not available, it would also be correct, but wedge-shaped is the better answer when both are present.
*Coffin-lid-like crystals*
- **Coffin-lid crystals** are characteristic of **struvite stones** (magnesium ammonium phosphate), which form in **alkaline urine** (pH >7) and are associated with **urease-producing bacteria** (e.g., Proteus, Klebsiella).
- Struvite stones are **radiopaque** and would be visible on X-ray, which contradicts this presentation.
- The patient has no signs of urinary tract infection.
*Red blood cell casts*
- **RBC casts** indicate **glomerular bleeding** and are seen in conditions like **glomerulonephritis**, not obstructive uropathy from stones.
- While **hematuria** (RBCs in urine) is common with nephrolithiasis, **RBC casts** are not typical and would suggest primary renal parenchymal disease.
*Hexagon-shaped crystals*
- **Hexagonal crystals** are pathognomonic for **cystine stones**, which occur in **cystinuria**, a rare autosomal recessive disorder of amino acid transport.
- Cystine stones are **weakly radiopaque** and would show faint opacity on X-ray.
- This condition typically presents in childhood or young adulthood, not at age 48, and has no association with gout.
Question 147: A 7-year-old girl is brought to the physician by her mother because of a 5-day history of fever, fatigue, and red spots on her body. Her temperature is 38.3°C (101.1°F), pulse is 115/min, and blood pressure is 100/60 mm Hg. Physical examination shows pallor and petechiae over the trunk and lower extremities. Laboratory studies show a hemoglobin concentration of 7 g/dL, a leukocyte count of 2,000/mm3, a platelet count of 40,000/mm3, and a reticulocyte count of 0.2%. Peripheral blood smear shows normochromic, normocytic cells. A bone marrow aspirate shows hypocellularity. Which of the following is the most likely cause of this patient's findings?
A. Idiopathic thrombocytopenic purpura
B. Aplastic anemia (Correct Answer)
C. Acute lymphoblastic leukemia
D. Multiple myeloma
E. Primary myelofibrosis
Explanation: ***Aplastic anemia***
- This diagnosis is strongly supported by the **pancytopenia** (anemia, leukopenia, thrombocytopenia), **fatigue**, and **petechiae**, coupled with a **hypocellular bone marrow** aspirate.
- The **low reticulocyte count** further indicates reduced erythropoiesis, a hallmark of bone marrow failure.
*Idiopathic thrombocytopenic purpura*
- This condition primarily causes isolated **thrombocytopenia**, while the patient also exhibits severe anemia and leukopenia.
- Bone marrow in ITP is typically normal or shows increased megakaryocytes, not hypocellularity.
*Acute lymphoblastic leukemia*
- While ALL can present with pancytopenia, fatigue, and petechiae, the bone marrow in ALL would show **hypercellularity** with an abundance of **blasts**, not hypocellularity.
- The absence of blasts on the peripheral smear and hypocellular marrow makes ALL unlikely.
*Multiple myeloma*
- This is a malignancy of **plasma cells** predominantly affecting older adults and is characterized by bone pain, hypercalcemia, renal failure, and monoclonal gammopathy.
- The patient's age and clinical presentation, especially the hypocellular bone marrow, are inconsistent with multiple myeloma.
*Primary myelofibrosis*
- Myelofibrosis typically presents with **extramedullary hematopoiesis**, splenomegaly, and a "dry tap" on bone marrow aspirate, which would show fibrosis.
- The patient's bone marrow is described as hypocellular, and no splenomegaly is mentioned, making myelofibrosis less likely.
Question 148: A 25-year-old woman comes to the physician because of a 2-week history of episodic bleeding from the nose and gums and one episode of blood in her urine. She was treated with chloramphenicol 1 month ago for Rickettsia rickettsii infection. Her pulse is 130/min, respirations are 22/min, and blood pressure is 105/70 mm Hg. Examination shows mucosal pallor, scattered petechiae, and ecchymoses on the extremities. Laboratory studies show:
Hemoglobin 6.3 g/dL
Hematocrit 26%
Leukocyte count 900/mm3 (30% neutrophils)
Platelet count 50,000/mm3
The physician recommends a blood transfusion and informs her of the risks and benefits. Which of the following red blood cell preparations will most significantly reduce the risk of transfusion-related cytomegalovirus infection?
A. Warming
B. Irradiation
C. Centrifugation
D. Washing
E. Leukoreduction (Correct Answer)
Explanation: ***Leukoreduction***
- **Cytomegalovirus (CMV)** is primarily transmitted via **leukocytes** in blood products, as it is a latent infection within these cells.
- **Leukoreduction** removes most white blood cells, thereby significantly reducing the risk of CMV transmission, especially in immunocompromised patients or those at high risk.
*Warming*
- **Warming blood** to body temperature before transfusion helps prevent hypothermia in the recipient and reduces the risk of cardiac arrhythmias.
- It does not, however, have any significant effect on reducing the transmission of infectious agents like CMV.
*Irradiation*
- **Irradiation** of blood products inactivates donor T lymphocytes, preventing **transfusion-associated graft-versus-host disease (TA-GVHD)**, predominantly in immunocompromised recipients.
- It does not effectively remove or inactivate viruses like CMV that reside within cells.
*Centrifugation*
- **Centrifugation** is used to separate blood components based on their different densities (e.g., plasma, platelets, red blood cells).
- While it separates components, it does not specifically remove or inactivate CMV-infected white blood cells from the remaining red blood cell product in a manner that significantly reduces infection risk.
*Washing*
- **Washing red blood cells** with saline removes plasma proteins, antibodies, and some white blood cells, which can prevent allergic reactions to plasma proteins or hyperkalemia.
- While it may remove some leukocytes, it is generally less effective than leukoreduction for preventing CMV transmission and is primarily indicated for other specific transfusion reactions.
Question 149: A 73-year-old man comes to the physician because of progressive fatigue and shortness of breath on exertion for 3 weeks. He has swelling of his legs. He has not had nausea or vomiting. His symptoms began shortly after he returned from a trip to Cambodia. He occasionally takes ibuprofen for chronic back pain. He has a history of arterial hypertension and osteoarthritis of both knees. He had an episode of pneumonia 4 months ago. His current medications include lisinopril and hydrochlorothiazide. He has no history of drinking or smoking. His temperature is 37°C (98.6°F), pulse is 101/min, and blood pressure is 135/76 mm Hg. Examination shows pitting edema of the upper and lower extremities. Laboratory studies show:
Hemoglobin 14.1 g/dL
Leukocyte count 6,800/mm3
Platelet count 216,000/mm3
Serum
Urea nitrogen 26 mg/dL
Creatinine 2.9 mg/dL
Albumin 1.6 g/dL
Urine
Blood negative
Protein 4+
Glucose negative
Renal biopsy with Congo red stain shows apple-green birefringence under polarized light. Further evaluation of this patient is most likely to show which of the following findings?
A. Positive interferon-γ release assay
B. Dilated bronchi on chest CT
C. Elevated anti-citrullinated peptide antibodies
D. Positive HLA-B27 test
E. Rouleaux formation on peripheral smear (Correct Answer)
Explanation: ***Rouleaux formation on peripheral smear***
- The renal biopsy showing **apple-green birefringence** with Congo red stain is pathognomonic for **amyloidosis**.
- The clinical presentation of **nephrotic syndrome** (massive proteinuria, hypoalbuminemia, edema) with renal amyloidosis in an elderly patient is most commonly due to **AL (light chain) amyloidosis** caused by plasma cell dyscrasia.
- AL amyloidosis is associated with **monoclonal gammopathy** which causes increased serum protein viscosity, leading to **rouleaux formation** (stacking of RBCs like coins) on peripheral blood smear.
- Further workup would typically show serum/urine protein electrophoresis with monoclonal protein and possibly bone marrow plasmacytosis.
*Positive interferon-γ release assay*
- This test diagnoses **latent or active tuberculosis**.
- While TB can cause **AA (secondary) amyloidosis** through chronic inflammation, and the patient traveled to an endemic area, the renal-limited presentation without active systemic infection makes AL amyloidosis more likely.
- AA amyloidosis typically presents with chronic inflammatory conditions lasting months to years.
*Dilated bronchi on chest CT*
- **Bronchiectasis** causes chronic inflammation and can lead to **AA amyloidosis**.
- However, a single episode of pneumonia 4 months ago is insufficient to cause the chronic inflammation needed for AA amyloidosis.
- This finding would not directly relate to the amyloid deposition causing current symptoms.
*Elevated anti-citrullinated peptide antibodies*
- These antibodies are highly specific for **rheumatoid arthritis**, which can cause AA amyloidosis.
- However, the patient has **osteoarthritis** (degenerative joint disease), not inflammatory arthritis.
- There are no clinical features suggesting RA (no joint inflammation, no morning stiffness).
*Positive HLA-B27 test*
- **HLA-B27** is associated with **seronegative spondyloarthropathies** which can rarely cause AA amyloidosis.
- The patient's back pain is attributed to chronic mechanical issues, not inflammatory spondyloarthropathy.
- This finding is unrelated to the renal amyloidosis presentation.
Question 150: A 23-year-old African American man presents to the emergency department with severe pain. The patient, who is a construction worker, was at work when he suddenly experienced severe pain in his arms, legs, chest, and back. He has experienced this before and was treated 2 months ago for a similar concern. His temperature is 100°F (37.8°C), blood pressure is 127/68 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for tenderness to palpation of the patient's legs, chest, abdomen, and arms. Laboratory values are obtained and shown below.
Hemoglobin: 10 g/dL
Hematocrit: 30%
Leukocyte count: 8,500/mm³ with normal differential
Platelet count: 199,000/mm³
Reticulocyte count: 8%
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.9 mEq/L
HCO3-: 25 mEq/L
BUN: 23 mg/dL
LDH: 327 U/L
Glucose: 99 mg/dL
Creatinine: 1.1 mg/dL
Ca2+: 10.2 mg/dL
AST: 12 U/L
ALT: 10 U/L
Which of the following is the most likely diagnosis?
A. Infection of the bone
B. Microvascular occlusion (Correct Answer)
C. Autoimmune hemolysis
D. Infarction of a major organ
E. Avascular necrosis
Explanation: ***Microvascular occlusion***
- The patient's presentation with **severe, diffuse pain** (arms, legs, chest, back) and a history of similar episodes, especially in an **African American male**, strongly suggests a **vaso-occlusive crisis** due to **sickle cell disease**.
- **Elevated reticulocyte count** (8%) and **mild anemia** (Hb 10 g/dL) with normal WBC and platelet counts are consistent with **chronic hemolysis** and the body's attempt to compensate, typical for sickle cell disease.
*Infection of the bone*
- While patients with **sickle cell disease** are prone to **osteomyelitis**, a bone infection generally presents with more localized pain and higher fever, not diffuse body pain.
- The presented vital signs and lab values, particularly the **normal leukocyte count**, do not strongly support an acute, widespread infectious process like osteomyelitis.
*Autoimmune hemolysis*
- **Autoimmune hemolysis** typically causes anemia, reticulocytosis, and elevated LDH, but it does not cause the characteristic **severe, diffuse body pain** seen in this patient.
- The patient's symptoms are more indicative of a vaso-occlusive event rather than immune-mediated destruction of red blood cells.
*Infarction of a major organ*
- While **sickle cell disease** can lead to organ infarction, the broad, diffuse pain described typically represents a **vaso-occlusive crisis** affecting multiple tissues rather than a single major organ.
- Lab results and symptoms do not point to a specific organ infarction, such as myocardial (normal AST/ALT) or renal (normal creatinine with mild BUN elevation which is usually present in dehydrated active people) infarction.
*Avascular necrosis*
- **Avascular necrosis** (AVN) is a complication of sickle cell disease, causing chronic joint pain, most commonly in the hips or shoulders.
- The patient's symptoms describe **acute, severe, diffuse pain** affecting multiple body parts, which is more characteristic of a vaso-occlusive crisis than the localized, chronic pain of avascular necrosis.
