A 15-year-old boy comes to the physician for the evaluation of progressive difficulty climbing stairs for the last 2 years. During this period, he has also had problems running and standing up from a seated position. He is at the 50th percentile for height and weight. Examination shows enlarged calf muscles bilaterally and a waddling gait. Which of the following is the most likely cause of this patient's condition?
Q182
A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney?
Q183
A 25-year-old male visits his primary care physician with complaints of hemoptysis and dysuria. Serum blood urea nitrogen and creatinine are elevated, blood pressure is 160/100 mm Hg, and urinalysis shows hematuria and RBC casts. A 24-hour urine excretion yields 1 gm/day protein. A kidney biopsy is obtained, and immunofluorescence shows linear IgG staining in the glomeruli. Which of the following antibodies is likely pathogenic for this patient’s disease?
Q184
A 45-year-old homeless man is brought to the emergency department after he was found unconscious at the park. The patient's past medical history is unknown; however, he was admitted to the emergency department 2 times over the past year for severe pain treated with hydromorphone and IV fluids. His temperature is 100°F (37.8°C), blood pressure is 97/48 mmHg, pulse is 140/min, respirations are 18/min, and oxygen saturation is 99% on room air. The patient smells of alcohol and is covered in emesis. Basic laboratory values are ordered as seen below.
Hemoglobin: 6 g/dL
Hematocrit: 20%
Leukocyte count: 6,500/mm^3 with normal differential
Platelet count: 197,000/mm^3
Reticulocyte count: 0.4%
Which of the following is associated with the most likely diagnosis?
Q185
A 14-year-old girl is brought to the emergency department because of a 3-day history of worsening confusion, high-grade fever, and a productive cough. She has had recurrent respiratory infections and bulky, foul-smelling, oily stools since infancy. She is at the 14th percentile for height and 8th percentile for weight. Despite appropriate care, the patient dies 2 days after admission. Autopsy of the lungs shows bronchial mucus plugging and bronchiectasis. Which of the following is the most likely underlying cause of this patient's condition?
Q186
A 64-year-old man presents to his primary care provider after noticing the development of a blistering rash. The patient states that his symptoms began 1 week ago after he noticed a blister develop on the inside of his mouth that eventually ruptured. Over the past several days, he has noticed several more blisters on his torso. The patient denies a fever or any other symptoms. He has a history of high blood pressure, for which he takes hydrochlorothiazide. He is otherwise healthy and denies any recent changes to his medication. Today, the patient’s temperature is 99.0°F (37.2°C), blood pressure is 124/84 mmHg, pulse is 66/min, and respirations are 12/min. On exam, the patient’s mouth is notable for a previously ruptured blister on his left buccal mucosa. On his left flank and anterior abdomen are scattered 10-15-cm bullae that appear flaccid and filled with serous fluid. The lesions are erythematous but there is no surrounding erythema. On manual rubbing of the skin near the lesions, new blisters form within minutes. Which of the following is involved in the pathogenesis of this disease?
Q187
A 63-year-old female enrolls in a research study evaluating the use of iron studies to screen for disease in a population of post-menopausal women. Per study protocol, past medical history and other identifying information is unknown. The patient's iron studies return as follows:
Serum iron: 200 µg/dL (normal 50–170 µg/dL)
TIBC: 220 µg/dL (normal 250–370 µg/dL)
Transferrin saturation: 91% (normal 15–50%)
Serum ferritin: 180 µg/L (normal 15-150 µg/L)
Which of the following is the most likely cause of these findings?
Q188
A 42-year-old man presents to his primary care physician complaining of subjective fever, cough, and night sweats. He states that over the past 2 months he has “not felt like myself.” He has lost 12 lbs over this time period. Two weeks ago, he started experiencing night sweats and cough. This morning he decided to take his temperature and reports it was “high.” He has a history of HIV and admits to inconsistently taking his anti-retrovirals. A chest radiograph reveals a cavitary lesion in the left upper lobe. An interferon-gamma release assay is positive, and the patient is started on appropriate antimicrobial therapy. A month later he is seen in clinic for follow-up. Lab work is obtained, as shown below:
Leukocyte count: 11,000/mm^3 with normal differential
Hemoglobin: 9.2 g/dL
Platelet count: 400,000/mm^3
Mean corpuscular volume (MCV): 75 µm^3
Based on these results, a peripheral smear is sent and shows Pappenheimer bodies. Which of the following is the most accurate test for the patient’s diagnosis?
Q189
A previously healthy 4-year-old boy is brought to the emergency department because of a 1-day history of pain and swelling of his left knee joint. He has not had any trauma to the knee. His family history is unremarkable except for a bleeding disorder in his maternal uncle. His temperature is 36.9°C (98.4°F). The left knee is erythematous, swollen, and tender; range of motion is limited. No other joints are affected. An x-ray of the knee shows an effusion but no structural abnormalities of the joint. Arthrocentesis is conducted. The synovial fluid is bloody. Further evaluation of this patient is most likely to show which of the following findings?
Q190
A 45-year-old man comes to the physician for a 2-day history of headache and breathlessness on exertion. During the same period, he has vomited twice and not passed urine. He also reports pain and stiffness in his fingers that has worsened progressively over the past 2 years. He has no history of serious illness and takes no medications. He does not smoke or drink alcohol. He is in moderate distress. His temperature is 37.2°C (98.9°F), pulse is 88/min, blood pressure is 170/100 mm Hg, and respirations are 24/min. Pulse oximetry on room air shows an oxygen saturation of 91%. Examination reveals pallor, 2+ pretibial edema, and jugular venous distention. The skin on the arms, chest, and upper back is coarse and thickened. Diffuse cutaneous hyperpigmentation and hypopigmented patches with perifollicular hypopigmentation are noted. Contractures are present in the proximal interphalangeal joints of both hands. Diffuse crackles are heard on auscultation of the chest. There is dullness to percussion and decreased breath sounds over both lung bases. S1 and S2 are normal. An S3 gallop is heard at the apex. The remainder of the examination shows no abnormalities. His hemoglobin concentration is 8.1 g/dL, and his serum creatinine is 5.3 mg/dL. Further evaluation of this patient is most likely to show which of the following?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 181: A 15-year-old boy comes to the physician for the evaluation of progressive difficulty climbing stairs for the last 2 years. During this period, he has also had problems running and standing up from a seated position. He is at the 50th percentile for height and weight. Examination shows enlarged calf muscles bilaterally and a waddling gait. Which of the following is the most likely cause of this patient's condition?
A. Large deletions (Correct Answer)
B. Frameshift mutation
C. Splice site mutation
D. Missense mutation
E. Nonsense mutation
Explanation: ***Large deletions***
- The presented symptoms (progressive difficulty climbing stairs, running, standing, enlarged calf muscles, waddling gait) are classic for **Duchenne muscular dystrophy (DMD)**.
- **Large deletions** (involving one or more exons) are the **most common cause of DMD**, accounting for approximately **60-70%** of cases.
- These deletions typically cause a **frameshift** that leads to a premature stop codon, resulting in absent or severely truncated **dystrophin protein**.
- The **dystrophin gene** is one of the largest human genes, making it particularly susceptible to deletion mutations.
*Frameshift mutation*
- A **frameshift mutation** (insertion or deletion of nucleotides not in multiples of three) leads to an altered reading frame, resulting in a **premature stop codon** downstream.
- While frameshifts do cause **DMD**, they are typically the **consequence** of deletions or small insertions/duplications, not a primary mutation category.
- The question asks for the underlying genetic cause, which is most commonly a large deletion.
*Splice site mutation*
- **Splice site mutations** affect the splicing of introns and exons, potentially leading to exon skipping or inclusion of intronic sequences.
- These account for a small percentage of **DMD** cases but are much less common than large deletions.
- While they can disrupt the reading frame, they represent a minority of causative mutations.
*Missense mutation*
- A **missense mutation** results in a single amino acid change, producing an altered but full-length protein.
- This type of mutation is more characteristic of **Becker muscular dystrophy (BMD)**, a milder form with later onset and slower progression.
- The severe, early-onset phenotype described here is typical of **DMD**, which requires near-complete absence of functional dystrophin.
*Nonsense mutation*
- A **nonsense mutation** introduces a premature stop codon, leading to a truncated protein.
- While nonsense mutations do cause **DMD**, they account for only about **10-15%** of cases as part of the broader category of point mutations.
- Large deletions remain significantly more common as the causative mutation type.
Question 182: A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney?
A. Granular immunofluorescence around the glomerular basement membrane
B. Lymphocytic infiltrate of the tubules and interstitium (Correct Answer)
C. Crescent formation in Bowman’s space
D. Drug precipitation in the renal tubules
E. Sloughing of proximal tubular epithelial cells
Explanation: ***Lymphocytic infiltrate of the tubules and interstitium***
- **Acute cell-mediated rejection** is primarily characterized by the infiltration of **T lymphocytes** and macrophages into the allograft, leading to inflammation and damage.
- This cellular infiltrate is typically observed in the **interstitium and tubules** of the transplanted kidney.
*Granular immunofluorescence around the glomerular basement membrane*
- This finding is characteristic of **immune complex-mediated glomerulonephritis**, such as post-streptococcal glomerulonephritis, and signifies deposition of immune complexes.
- It is not typical of acute cell-mediated rejection, which is driven by T-cells rather than circulating immune complexes.
*Crescent formation in Bowman’s space*
- **Crescents** in Bowman's space are indicative of rapidly progressive glomerulonephritis (RPGN), a severe form of glomerular inflammation usually associated with conditions like Goodpasture syndrome or ANCA-associated vasculitis.
- While crescentic glomerulonephritis can cause acute kidney injury, it is not the primary histological hallmark of acute cell-mediated transplant rejection.
*Drug precipitation in the renal tubules*
- **Drug precipitation** can occur with certain medications, leading to acute kidney injury (e.g., sulfonamides, methotrexate), but it is a chemical injury, not an immune-mediated rejection process.
- The patient's symptoms of fever and arthralgia, along with elevated creatinine, point towards an inflammatory immune response rather than drug toxicity alone.
*Sloughing of proximal tubular epithelial cells*
- **Sloughing of proximal tubular epithelial cells** is a hallmark of **acute tubular necrosis (ATN)**, often caused by ischemia or nephrotoxic agents.
- While ATN can also lead to elevated creatinine, the presence of fever and arthralgia, plus the context of transplantation, makes acute cell-mediated rejection a more likely diagnosis.
Question 183: A 25-year-old male visits his primary care physician with complaints of hemoptysis and dysuria. Serum blood urea nitrogen and creatinine are elevated, blood pressure is 160/100 mm Hg, and urinalysis shows hematuria and RBC casts. A 24-hour urine excretion yields 1 gm/day protein. A kidney biopsy is obtained, and immunofluorescence shows linear IgG staining in the glomeruli. Which of the following antibodies is likely pathogenic for this patient’s disease?
A. Anti-phospholipid antibody
B. Anti-neutrophil cytoplasmic antibody (C-ANCA)
C. Anti-neutrophil perinuclear antibody (P-ANCA)
D. Anti-glomerular basement membrane antibody (Anti-GBM) (Correct Answer)
E. Anti-DNA antibody
Explanation: ***Anti-glomerular basement membrane antibody (Anti-GBM)***
- The combination of **hemoptysis** (indicating pulmonary hemorrhage), **dysuria** (indicating renal involvement), rapidly progressive renal failure (elevated BUN/creatinine, hematuria, RBC casts, hypertension, proteinuria), and **linear IgG staining** on kidney biopsy is highly characteristic of **Goodpasture's syndrome**, which is caused by anti-GBM antibodies.
- These antibodies target collagen type IV in the **glomerular and alveolar basement membranes**, leading to a dual presentation of glomerulonephritis and pulmonary hemorrhage.
*Anti-phospholipid antibody*
- These antibodies are associated with a **hypercoagulable state**, leading to recurrent venous or arterial thromboses, and recurrent pregnancy loss.
- They do not typically cause **hemoptysis** or **glomerulonephritis** with linear IgG staining.
*Anti-neutrophil cytoplasmic antibody (C-ANCA)*
- **C-ANCA** is associated with **Wegener's granulomatosis** (granulomatosis with polyangiitis), a small vessel vasculitis that can cause pulmonary-renal syndrome but would show **pauci-immune glomerulonephritis** (no or minimal immune deposits) on biopsy, not linear IgG staining.
- The staining pattern on immunofluorescence is key to differentiating this from Goodpasture's.
*Anti-neutrophil perinuclear antibody (P-ANCA)*
- **P-ANCA** is associated with microscopic polyangiitis and Churg-Strauss syndrome, which are also causes of **pauci-immune vasculitis** affecting the lungs and kidneys.
- Similar to C-ANCA, these conditions do not present with **linear IgG staining** on immunofluorescence.
*Anti-DNA antibody*
- **Anti-DNA antibodies**, particularly anti-dsDNA, are characteristic of **systemic lupus erythematosus (SLE)**, which can cause glomerulonephritis (lupus nephritis).
- Lupus nephritis typically presents with **granular immune complex deposits** on immunofluorescence, not linear IgG staining.
Question 184: A 45-year-old homeless man is brought to the emergency department after he was found unconscious at the park. The patient's past medical history is unknown; however, he was admitted to the emergency department 2 times over the past year for severe pain treated with hydromorphone and IV fluids. His temperature is 100°F (37.8°C), blood pressure is 97/48 mmHg, pulse is 140/min, respirations are 18/min, and oxygen saturation is 99% on room air. The patient smells of alcohol and is covered in emesis. Basic laboratory values are ordered as seen below.
Hemoglobin: 6 g/dL
Hematocrit: 20%
Leukocyte count: 6,500/mm^3 with normal differential
Platelet count: 197,000/mm^3
Reticulocyte count: 0.4%
Which of the following is associated with the most likely diagnosis?
A. Iron deficiency
B. Parvovirus B19 infection (Correct Answer)
C. Folate deficiency
D. Vitamin B12 deficiency
E. Benign genetic carrier condition
Explanation: ***Parvovirus B19 infection***
- This patient presents with **severe anemia (Hb 6 g/dL)** and **profound reticulocytopenia (0.4%)** - the combination of severe anemia with a markedly suppressed reticulocyte count indicates **bone marrow suppression** affecting red cell production.
- **Parvovirus B19** specifically targets **erythroid progenitor cells** in the bone marrow, causing **transient aplastic crisis** characterized by acute cessation of red blood cell production (hence the reticulocytopenia).
- While aplastic crisis classically occurs in patients with **underlying chronic hemolytic anemias** (e.g., sickle cell disease), the patient's history of **recurrent severe pain episodes** requiring opioid analgesia suggests a possible undiagnosed hemolytic disorder. In such patients, Parvovirus B19 infection can cause life-threatening anemia because the bone marrow cannot compensate for ongoing hemolysis.
- The **homeless status** increases risk of viral infections, and the acute presentation with fever supports an infectious etiology.
- **Key diagnostic clue**: Severe anemia + reticulocytopenia (not reticulocytosis) = bone marrow suppression, most consistent with Parvovirus B19 aplastic crisis.
*Iron deficiency*
- **Iron deficiency anemia** typically presents with **microcytic, hypochromic** red cells and develops gradually over time.
- Importantly, iron deficiency would trigger a **compensatory reticulocytosis** (elevated reticulocyte count) as the bone marrow attempts to respond to anemia - the opposite of what is seen here with reticulocytopenia.
- Does not explain the **acute presentation** with profound bone marrow suppression.
*Folate deficiency*
- **Folate deficiency** causes **macrocytic anemia** (elevated MCV) and is common in chronic alcoholics due to poor nutrition.
- While folate deficiency can impair red cell production, it typically shows an **inadequate reticulocyte response** (low but not profoundly suppressed) rather than the severe reticulocytopenia (0.4%) seen here.
- The **megaloblastic changes** from folate deficiency develop gradually, not acutely as in this presentation.
*Vitamin B12 deficiency*
- **Vitamin B12 deficiency** also causes **macrocytic anemia** with elevated MCV and may present with neurological symptoms (subacute combined degeneration).
- Like folate deficiency, B12 deficiency shows **ineffective erythropoiesis** but not the profound acute reticulocytopenia characteristic of bone marrow suppression.
- The time course is typically chronic, not acute as presented.
*Benign genetic carrier condition*
- A **benign genetic carrier condition** (e.g., thalassemia trait) causes **mild, chronic microcytic anemia** that is typically asymptomatic and stable.
- Carrier states do not cause **severe acute anemia** or **reticulocytopenia** - in fact, thalassemia trait often shows normal or elevated red cell counts with low MCV.
- Does not explain the acute clinical decompensation, fever, or profound bone marrow suppression.
Question 185: A 14-year-old girl is brought to the emergency department because of a 3-day history of worsening confusion, high-grade fever, and a productive cough. She has had recurrent respiratory infections and bulky, foul-smelling, oily stools since infancy. She is at the 14th percentile for height and 8th percentile for weight. Despite appropriate care, the patient dies 2 days after admission. Autopsy of the lungs shows bronchial mucus plugging and bronchiectasis. Which of the following is the most likely underlying cause of this patient's condition?
A. Mutation of DNAI1 gene on chromosome 9
B. Deficiency in alpha-1 antitrypsin
C. Deficiency in apolipoprotein B-48
D. Deficiency in adenosine deaminase
E. Deletion of phenylalanine codon on chromosome 7 (Correct Answer)
Explanation: ***Deletion of phenylalanine codon on chromosome 7***
- The patient's presentation of **recurrent respiratory infections**, **bronchial mucus plugging**, **bronchiectasis**, and **malabsorption** (foul-smelling, oily stools, failure to thrive) is classic for **cystic fibrosis**.
- **Cystic fibrosis** is most commonly caused by a **deletion of three base pairs** coding for phenylalanine at position 508 (**ΔF508**) on the **CFTR gene** located on **chromosome 7**.
*Mutation of DNAI1 gene on chromosome 9*
- A mutation in the **DNAI1 gene** on chromosome 9 is associated with **primary ciliary dyskinesia (PCD)**.
- While PCD can cause recurrent respiratory infections and bronchiectasis due to impaired mucociliary clearance, it typically **does not involve the pancreatic insufficiency** and malabsorption suggested by the oily stools and failure to thrive in this patient.
*Deficiency in alpha-1 antitrypsin*
- **Alpha-1 antitrypsin deficiency** primarily leads to early-onset **emphysema** and liver disease, not typically the severe pancreatic insufficiency and recurrent bacterial infections seen in cystic fibrosis.
- While it can cause lung damage, the absence of symptoms related to **pancreatic dysfunction** makes this less likely.
*Deficiency in apolipoprotein B-48*
- A deficiency in **apolipoprotein B-48** is associated with **abetalipoproteinemia**, a disorder characterized by the inability to synthesize chylomicrons, leading to severe malabsorption of dietary fats and fat-soluble vitamins.
- While it causes malabsorption and greasy stools, it **does not typically present with recurrent respiratory infections, mucus plugging, and bronchiectasis**, which are prominent features in this case.
*Deficiency in adenosine deaminase*
- A deficiency in **adenosine deaminase (ADA)** leads to **severe combined immunodeficiency (SCID)**, characterized by profound lymphopenia and recurrent infections (bacterial, viral, fungal).
- While SCID causes recurrent infections and failure to thrive, it typically **does not present with the specific pulmonary pathology of mucus plugging and bronchiectasis**, nor the **pancreatic exocrine insufficiency** suggested by the oily stools.
Question 186: A 64-year-old man presents to his primary care provider after noticing the development of a blistering rash. The patient states that his symptoms began 1 week ago after he noticed a blister develop on the inside of his mouth that eventually ruptured. Over the past several days, he has noticed several more blisters on his torso. The patient denies a fever or any other symptoms. He has a history of high blood pressure, for which he takes hydrochlorothiazide. He is otherwise healthy and denies any recent changes to his medication. Today, the patient’s temperature is 99.0°F (37.2°C), blood pressure is 124/84 mmHg, pulse is 66/min, and respirations are 12/min. On exam, the patient’s mouth is notable for a previously ruptured blister on his left buccal mucosa. On his left flank and anterior abdomen are scattered 10-15-cm bullae that appear flaccid and filled with serous fluid. The lesions are erythematous but there is no surrounding erythema. On manual rubbing of the skin near the lesions, new blisters form within minutes. Which of the following is involved in the pathogenesis of this disease?
A. IgA antibodies depositing in the dermal papillae
B. Autoantibodies against hemidesmosomes
C. Exotoxin destroying keratinocyte attachments
D. Viral infection of skin
E. IgG against transmembrane proteins between cells (Correct Answer)
Explanation: ***IgG against transmembrane proteins between cells***
- This clinical presentation, including flaccid bullae, Nikolsky sign (new blisters with manual rubbing), and oral involvement, is characteristic of **pemphigus vulgaris**.
- Pemphigus vulgaris is caused by **IgG autoantibodies** targeting **desmoglein 1** and **desmoglein 3**, which are transmembrane proteins forming desmosomes that connect keratinocytes.
*IgA antibodies depositing in the dermal papillae*
- This describes the pathogenesis of **dermatitis herpetiformis**, which presents with intensely pruritic papulovesicular lesions, typically on extensor surfaces.
- The lesions in dermatitis herpetiformis are small, grouped vesicles, not the large, flaccid bullae seen in this patient.
*Autoantibodies against hemidesmosomes*
- This mechanism is characteristic of **bullous pemphigoid**, which typically presents with tense bullae that do not rupture easily and are often associated with pruritus.
- Unlike pemphigus vulgaris, bullous pemphigoid usually spares the oral mucosa, and the Nikolsky sign is typically absent.
*Exotoxin destroying keratinocyte attachments*
- This mechanism is seen in conditions like **staphylococcal scalded skin syndrome (SSSS)**, caused by exfoliating toxins that cleave **desmoglein 1**.
- SSSS typically presents with diffuse erythema and superficial epidermal peeling, often in children, and the patient's history does not suggest an acute infection.
*Viral infection of skin*
- Viral infections leading to blistering rashes, such as **herpes simplex** or **varicella-zoster virus**, typically cause painful, grouped vesicles on an erythematous base.
- The extensive, flaccid bullae and lack of fever or prodromal symptoms are inconsistent with a primary viral blistering eruption.
Question 187: A 63-year-old female enrolls in a research study evaluating the use of iron studies to screen for disease in a population of post-menopausal women. Per study protocol, past medical history and other identifying information is unknown. The patient's iron studies return as follows:
Serum iron: 200 µg/dL (normal 50–170 µg/dL)
TIBC: 220 µg/dL (normal 250–370 µg/dL)
Transferrin saturation: 91% (normal 15–50%)
Serum ferritin: 180 µg/L (normal 15-150 µg/L)
Which of the following is the most likely cause of these findings?
A. Iron deficiency
B. Lead poisoning
C. Excess iron absorption (Correct Answer)
D. Pregnancy
E. Chronic inflammation
Explanation: ***Excess iron absorption***
- The combination of **elevated serum iron**, **high transferrin saturation**, and **normal to elevated ferritin** is characteristic of **iron overload** due to excess absorption.
- Reduced **TIBC** (Total Iron-Binding Capacity) further supports iron overload, as fewer binding sites are available for iron due to saturation.
*Iron deficiency*
- **Iron deficiency** would show **low serum iron**, **low ferritin**, **high TIBC**, and **low transferrin saturation**.
- This clinical picture is the opposite of the given lab values, indicating a surplus, not a deficit, of iron.
*Lead poisoning*
- While **lead poisoning** can affect red blood cell production and lead to **anemia**, it typically causes microcytic, hypochromic anemia and does not directly result in the described pattern of **iron overload**.
- Iron studies in lead poisoning may show normal or mildly elevated ferritin, but not the high serum iron and transferrin saturation seen here.
*Pregnancy*
- **Pregnancy** is a state of **increased iron demand**, and iron studies typically show **dilutional anemia**, **low serum iron**, and **increased TIBC** as the body tries to absorb more iron.
- This patient is **post-menopausal** and, therefore, pregnancy is not a relevant condition for these findings.
*Chronic inflammation*
- **Chronic inflammation** (anemia of chronic disease) would typically present with **low serum iron**, **low TIBC**, but **normal or elevated ferritin** (as ferritin is an acute phase reactant).
- The **high transferrin saturation** seen in this patient is not consistent with anemia of chronic disease.
Question 188: A 42-year-old man presents to his primary care physician complaining of subjective fever, cough, and night sweats. He states that over the past 2 months he has “not felt like myself.” He has lost 12 lbs over this time period. Two weeks ago, he started experiencing night sweats and cough. This morning he decided to take his temperature and reports it was “high.” He has a history of HIV and admits to inconsistently taking his anti-retrovirals. A chest radiograph reveals a cavitary lesion in the left upper lobe. An interferon-gamma release assay is positive, and the patient is started on appropriate antimicrobial therapy. A month later he is seen in clinic for follow-up. Lab work is obtained, as shown below:
Leukocyte count: 11,000/mm^3 with normal differential
Hemoglobin: 9.2 g/dL
Platelet count: 400,000/mm^3
Mean corpuscular volume (MCV): 75 µm^3
Based on these results, a peripheral smear is sent and shows Pappenheimer bodies. Which of the following is the most accurate test for the patient’s diagnosis?
A. Hemoglobin electrophoresis
B. Methylmalonic acid level
C. Genetic testing
D. Iron studies
E. Prussian blue staining (Correct Answer)
Explanation: ***Prussian blue staining***
- The patient presents with **microcytic anemia** (MCV 75 µm³, Hb 9.2 g/dL) and **Pappenheimer bodies** on peripheral smear, which are **iron-containing granules** suggestive of **sideroblastic anemia**.
- In the context of **anti-tuberculosis therapy** (especially **isoniazid**), drug-induced sideroblastic anemia is highly likely, as isoniazid interferes with **pyridoxine (vitamin B6)** metabolism, which is essential for heme synthesis.
- **Prussian blue staining of bone marrow** is the **gold standard and most accurate test** for diagnosing sideroblastic anemia, as it definitively demonstrates **ring sideroblasts** (erythroblasts with iron-loaded mitochondria forming a perinuclear ring).
- This is the **definitive diagnostic test** that directly visualizes the pathologic finding.
*Iron studies*
- While **iron studies** (elevated serum iron, ferritin, and transferrin saturation with low/normal TIBC) are **suggestive** of sideroblastic anemia, they are **not diagnostic**.
- Iron studies help support the diagnosis and differentiate from iron deficiency anemia, but they cannot definitively confirm sideroblastic anemia.
- The question asks for the **most accurate test**, which requires definitive pathologic confirmation, not just supportive laboratory findings.
*Hemoglobin electrophoresis*
- This test is used to diagnose **hemoglobinopathies** such as **thalassemia** or **sickle cell disease**.
- While thalassemia can cause microcytic anemia, the presence of **Pappenheimer bodies** and the clinical context of **TB treatment** make drug-induced sideroblastic anemia the primary diagnosis.
*Methylmalonic acid level*
- **Methylmalonic acid** levels are elevated in **vitamin B12 deficiency**, which causes **macrocytic anemia** (high MCV).
- The patient has **microcytic anemia** (MCV 75 µm³), making B12 deficiency inconsistent with the presentation.
*Genetic testing*
- **Genetic testing** identifies **hereditary sideroblastic anemia**, a rare congenital disorder.
- This patient's sideroblastic anemia is **acquired** (drug-induced by isoniazid), making genetic testing unnecessary.
- Even if genetic testing were relevant, **Prussian blue staining** would still be needed first to confirm the diagnosis of sideroblastic anemia.
Question 189: A previously healthy 4-year-old boy is brought to the emergency department because of a 1-day history of pain and swelling of his left knee joint. He has not had any trauma to the knee. His family history is unremarkable except for a bleeding disorder in his maternal uncle. His temperature is 36.9°C (98.4°F). The left knee is erythematous, swollen, and tender; range of motion is limited. No other joints are affected. An x-ray of the knee shows an effusion but no structural abnormalities of the joint. Arthrocentesis is conducted. The synovial fluid is bloody. Further evaluation of this patient is most likely to show which of the following findings?
A. Prolonged prothrombin time
B. Synovial fluid leukocytosis
C. Elevated antinuclear antibody levels
D. Prolonged partial thromboplastin time (Correct Answer)
E. Decreased platelet count
Explanation: ***Prolonged partial thromboplastin time***
- The clinical presentation of a young boy with **spontaneous hemarthrosis** (bloody synovial fluid in the knee) and a family history of a **bleeding disorder in a maternal uncle** is highly suggestive of **hemophilia A or B**.
- Both hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) present with a **prolonged PTT** due to impaired intrinsic coagulation pathway, while PT and platelet count typically remain normal.
*Prolonged prothrombin time*
- A prolonged **prothrombin time (PT)** primarily indicates a deficiency in the **extrinsic coagulation pathway**, involving factor VII, or severe deficiencies in common pathway factors (II, V, X, fibrinogen).
- This is not characteristic of hemophilia A or B, which are deficiencies in the **intrinsic pathway**.
*Synovial fluid leukocytosis*
- **Synovial fluid leukocytosis** (increased white blood cells) is typically seen in **inflammatory or infectious arthritis**, such as septic arthritis or juvenile idiopathic arthritis.
- While the knee is swollen and tender, the **bloody synovial fluid without trauma** points away from infection and towards a bleeding disorder.
*Elevated antinuclear antibody levels*
- **Elevated antinuclear antibody (ANA) levels** are a hallmark of **systemic autoimmune diseases** like systemic lupus erythematosus (SLE) or certain forms of juvenile idiopathic arthritis.
- These conditions do not typically present with spontaneous gross hemarthrosis as the primary symptom, nor would they explain the family history of a bleeding disorder.
*Decreased platelet count*
- A **decreased platelet count (thrombocytopenia)** would lead to a bleeding disorder characterized by mucocutaneous bleeding (e.g., petechiae, purpura, epistaxis) rather than deep joint bleeds.
- Platelet dysfunction or thrombocytopenia would cause a **prolonged bleeding time**, not typically a prolonged PTT, and the overall clinical picture does not align with a primary platelet disorder.
Question 190: A 45-year-old man comes to the physician for a 2-day history of headache and breathlessness on exertion. During the same period, he has vomited twice and not passed urine. He also reports pain and stiffness in his fingers that has worsened progressively over the past 2 years. He has no history of serious illness and takes no medications. He does not smoke or drink alcohol. He is in moderate distress. His temperature is 37.2°C (98.9°F), pulse is 88/min, blood pressure is 170/100 mm Hg, and respirations are 24/min. Pulse oximetry on room air shows an oxygen saturation of 91%. Examination reveals pallor, 2+ pretibial edema, and jugular venous distention. The skin on the arms, chest, and upper back is coarse and thickened. Diffuse cutaneous hyperpigmentation and hypopigmented patches with perifollicular hypopigmentation are noted. Contractures are present in the proximal interphalangeal joints of both hands. Diffuse crackles are heard on auscultation of the chest. There is dullness to percussion and decreased breath sounds over both lung bases. S1 and S2 are normal. An S3 gallop is heard at the apex. The remainder of the examination shows no abnormalities. His hemoglobin concentration is 8.1 g/dL, and his serum creatinine is 5.3 mg/dL. Further evaluation of this patient is most likely to show which of the following?
A. Decreased serum complement levels
B. Decreased serum haptoglobin levels (Correct Answer)
C. Increased anti-CCP antibody titers
D. Increased anticentromere antibody titers
E. Increased total iron binding capacity
Explanation: ***Decreased serum haptoglobin levels***
- This patient presents with symptoms and signs highly suggestive of **scleroderma renal crisis** (hypertension, acute kidney injury, headache, breathlessness, oliguria) in the context of long-standing systemic sclerosis (skin thickening, joint contractures, pulmonary findings). **Microangiopathic hemolytic anemia (MAHA)**, characterized by red blood cell fragmentation and consumption of haptoglobin, is a common complication of scleroderma renal crisis.
- **Decreased haptoglobin** levels occur as it binds free hemoglobin released from destroyed red blood cells, indicating active hemolysis. The **anemia (Hb 8.1 g/dL)** in this patient, along with the renal crisis and other systemic sclerosis features, makes MAHA a strong consideration.
*Decreased serum complement levels*
- Decreased complement levels (C3, C4) are typically associated with **immune complex-mediated diseases** like **systemic lupus erythematosus (SLE)** or **cryoglobulinemia**.
- While systemic sclerosis can overlap with other autoimmune conditions, profoundly low complement levels as a primary feature of scleroderma renal crisis or MAHA are not typical.
*Increased anti-CCP antibody titers*
- **Anti-cyclic citrullinated peptide (anti-CCP) antibodies** are highly specific for **rheumatoid arthritis**.
- The patient's presentation with prominent skin thickening, renal crisis, and lung involvement is not characteristic of rheumatoid arthritis.
*Increased anticentromere antibody titers*
- **Anticentromere antibodies** are specific for the **limited cutaneous form of systemic sclerosis (CREST syndrome)**.
- While the patient has systemic sclerosis, the severe multi-organ involvement (renal crisis, extensive skin thickening, pulmonary fibrosis) is more consistent with **diffuse cutaneous systemic sclerosis**, which is typically associated with **anti-Scl-70 (anti-topoisomerase I) antibodies**, not anticentromere.
*Increased total iron binding capacity*
- **Increased total iron binding capacity (TIBC)** is characteristic of **iron deficiency anemia**, where the body attempts to absorb more iron due to low stores.
- While the patient has anemia, the context of acute kidney injury and likely MAHA points towards different underlying mechanisms of anemia, such as chronic disease, hemolysis, or uremic suppression of erythropoiesis, rather than primary iron deficiency causing an increased TIBC.
