A 49-year-old obese woman presents with a chronic non-healing ulcer on the right medial malleolus. Past medical history is significant for type 2 diabetes mellitus, diagnosed 10 years ago, poorly managed with metformin. Review of systems is significant for a recurrent white vaginal discharge. The patient is afebrile, and her vital signs are within normal limits. Her BMI is 31 kg/m2. On physical examination, there is a 2 cm by 2 cm nontender, erythematous shallow ulcer present over the right medial malleolus. Sensation is decreased symmetrically in the lower extremities below the level of the midcalf. Which of the following histopathological findings would most likely be seen in the peripheral nerves in this patient?
Q282
A 2-year-old boy is brought to the pediatrician for recurrent nosebleeds. The boy was adopted two months ago and the parents have no record of his medical or family history. They report that the child has had frequent prolonged nosebleeds several times per week. Despite them applying pressure on the distal aspect of the nares and keeping his head elevated, the bleeding generally continues for hours. On exam, the boy appears pale and lethargic. A blood sample is obtained but the child bleeds through multiple pieces of gauze. No agglutination is observed when ristocetin is added to the patient’s blood. The addition of normal plasma to the sample still does not lead to agglutination. This patient has a condition that is most consistent with which of the following modes of transmission?
Q283
A 25-year-old man is brought to the emergency department by ambulance after a motor vehicle accident. His car was rear-ended by a drunk driver while he was stopped at a traffic light. At the scene, he was noted to have multiple small lacerations over his upper extremities from broken glass. He has otherwise been healthy, does not smoke, and drinks 5 beers per night. He notes that he recently started trying out a vegan diet and moved to an apartment located in a historic neighborhood that was built in the 1870s. Physical exam reveals several small lacerations on his arms bilaterally but is otherwise unremarkable. A complete blood workup is sent and some of the notable findings are shown below:
Hemoglobin: 12.1 g/dL (normal: 13.5-17.5 g/dL)
Platelet count: 261,000/mm^3 (normal: 150,000-400,000/mm^3)
Mean corpuscular volume: 74 µm^3 (normal: 80-100 µm^3)
Further testing using serum hemoglobin electrophoresis reveals:
Hemoglobin A1 92% (normal 95-98%)
Hemoglobin A2: 6% (normal: 1.5-3.1%)
Which of the following cell morphologies would most likely be seen on blood smear in this patient?
Q284
A 64-year-old man comes to the physician because of fatigue and decreased urinary frequency for 6 months. His pulse is 86/min and blood pressure is 150/90 mm Hg. Examination shows 1+ edema on bilateral ankles. His serum creatinine is 2 mg/dL and blood urea nitrogen is 28 mg/dL. Urinalysis shows proteinuria. A photomicrograph of a biopsy specimen from the patient's kidney is shown. Which of the following is the most likely explanation for the patient’s biopsy findings?
Q285
A 12-year-old boy is brought to an outpatient clinic by his mother, who noticed that her son’s urine has been dark for the past 4 days. She initially attributed this to inadequate hydration, so she monitored her son’s fluid intake and encouraged him to drink more water. However, she noticed that the color of the urine kept getting darker until it began to resemble cola. The boy’s medical history is significant for a sore throat approx. 2 weeks ago, which resolved without medication or treatment. The boy has also been complaining of pain in his ankles, which he first noticed shortly after soccer practice 1 week ago. He has had no pain during urination or urethral discharge, however, and does not have any history of previous episodes of cola-colored urine or passage of blood in the urine. However, the boy has been experiencing intermittent episodes of abdominal pain for the past 3 days. The boy also has wheals on his torso, legs, and buttocks, which his mother attributes to seasonal allergies. Physical examination reveals an alert child who is not in obvious distress but who has a mild conjunctival pallor. Vital signs include: respiratory rate is 22/min, temperature is 36.7°C (98.0°F), and blood pressure is 130/90 mm Hg. Examination of the musculoskeletal system reveals multiple skin lesions (see image). Which of the following laboratory findings is most likely associated with this patient’s clinical presentation?
Q286
A 55-year-old male presents to his primary care physician complaining of right hip pain for the past eight months. He also reports progressive loss of hearing over the same time period. Radiographic imaging reveals multiple areas of expanded bony cortices and coarsened trabeculae in his right hip and skull. Laboratory analysis reveals an isolated elevation in alkaline phosphatase with normal levels of serum calcium and phosphate. Which of the following histologic findings is most likely to be seen if one of the lesions were biopsied?
Q287
A 57-year-old man presents to his primary care physician with a 2-month history of right upper and lower extremity weakness. He noticed the weakness when he started falling far more frequently while running errands. Since then, he has had increasing difficulty with walking and lifting objects. His past medical history is significant only for well-controlled hypertension, but he says that some members of his family have had musculoskeletal problems. His right upper extremity shows forearm atrophy and depressed reflexes while his right lower extremity is hypertonic with a positive Babinski sign. Which of the following is most likely associated with the cause of this patient's symptoms?
Q288
A 3-year-old girl is brought to her pediatrician because of a nosebleed that will not stop. Her parents say that she started having a nosebleed about 1 hour prior to presentation. Since then they have not been able to stop the bleeding. Her past medical history is remarkable for asthma, and she has a cousin who has been diagnosed with hemophilia. Physical exam reveals diffuse petechiae and purpura. A panel of bleeding tests are obtained with the following results:
Bleeding time: 11 minutes
Prothrombin time: 14 seconds
Partial thromboplastin time: 32 seconds
Platelet count: 195,000/mm^3
Peripheral blood smear shows normal cell morphology. Which of the following characteristics is most likely true about this patient?
Q289
An 8-year-old boy is brought to the physician by his parents because of fever for 3 days. During the period, he has had fatigue, severe burning with urination, and increased urination. The mother reports that his urine has red streaks and a “strange” odor. He has taken acetaminophen twice a day for the past two days with no improvement in his symptoms. He has had multiple ear infections in the past but has been healthy in the past year. His immunizations are up-to-date. He appears uncomfortable. His temperature is 39°C (102.2°F). Examination shows right-sided costovertebral angle tenderness. Laboratory studies show a leukocyte count of 16,000/cm3 and an erythrocyte sedimentation rate of 40 mm/hr. Urine dipstick shows leukocyte esterase and nitrites. Urinalysis shows:
Blood 2+
Protein 2+
WBC 24/hpf
RBC 50/hpf
RBC casts none
WBC casts numerous
Granular casts none
Urine cultures are sent to the laboratory. Damage to which of the following structures is the most likely cause of this patient's hematuria?
Q290
A 42-year-old woman comes to the physician because of a 10-month history of joint pain and stiffness in her wrists and fingers. The symptoms are worse in the morning and improve with activity. Physical examination shows swelling and warmth over the MCP and wrist joints in both hands. An x-ray of the hands is shown. Synovial biopsy from an affected joint would most likely show which of the following?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 281: A 49-year-old obese woman presents with a chronic non-healing ulcer on the right medial malleolus. Past medical history is significant for type 2 diabetes mellitus, diagnosed 10 years ago, poorly managed with metformin. Review of systems is significant for a recurrent white vaginal discharge. The patient is afebrile, and her vital signs are within normal limits. Her BMI is 31 kg/m2. On physical examination, there is a 2 cm by 2 cm nontender, erythematous shallow ulcer present over the right medial malleolus. Sensation is decreased symmetrically in the lower extremities below the level of the midcalf. Which of the following histopathological findings would most likely be seen in the peripheral nerves in this patient?
A. Reduced axonal fiber diameter and fiber density (Correct Answer)
B. Accumulation of beta-pleated sheets of amyloid protein
C. Wallerian degeneration
D. Lymphocytic infiltration of the endoneurium
E. Acute perivascular inflammation
Explanation: ***Reduced axonal fiber diameter and fiber density***
- This is characteristic of **diabetic neuropathy**, where chronic hyperglycemia leads to damage and degeneration of nerve fibers, particularly **small myelinated and unmyelinated fibers**.
- The patient's history of poorly controlled **type 2 diabetes** for 10 years and decreased sensation in the lower extremities strongly suggest this microvascular complication.
*Accumulation of beta-pleated sheets of amyloid protein*
- This finding is characteristic of **amyloid neuropathy**, a type of peripheral neuropathy caused by the deposition of **amyloid protein** in nerve tissue.
- While amyloidosis can cause neuropathy, it is not the primary or most common cause in a patient with a long history of poorly controlled type 2 diabetes.
*Wallerian degeneration*
- **Wallerian degeneration** is an active process of degeneration that occurs in the distal stump of an axon after it has been transected or crushed.
- While parts of diabetic neuropathy can involve axonal damage, Wallerian degeneration specifically refers to acute, complete axonal disruption, rather than the chronic, progressive process seen in diabetes.
*Lymphocytic infiltration of the endoneurium*
- **Lymphocytic infiltration** of the endoneurium is typically seen in **inflammatory neuropathies** such as **Guillain-Barré syndrome** or **chronic inflammatory demyelinating polyneuropathy (CIDP)**.
- The patient's presentation with chronic, progressive sensory loss in the context of diabetes does not suggest an acute or chronic inflammatory polyneuropathy.
*Acute perivascular inflammation*
- **Acute perivascular inflammation** is a feature of **vasculitic neuropathies**, where inflammation of the blood vessels supplying nerves leads to nerve damage.
- While diabetes can have microvascular complications, the primary mechanism of diabetic neuropathy is metabolic and ischemic damage to the nerves themselves, not acute inflammation of the surrounding vessels as the predominant histopathological feature.
Question 282: A 2-year-old boy is brought to the pediatrician for recurrent nosebleeds. The boy was adopted two months ago and the parents have no record of his medical or family history. They report that the child has had frequent prolonged nosebleeds several times per week. Despite them applying pressure on the distal aspect of the nares and keeping his head elevated, the bleeding generally continues for hours. On exam, the boy appears pale and lethargic. A blood sample is obtained but the child bleeds through multiple pieces of gauze. No agglutination is observed when ristocetin is added to the patient’s blood. The addition of normal plasma to the sample still does not lead to agglutination. This patient has a condition that is most consistent with which of the following modes of transmission?
A. X-linked dominant
B. Mitochondrial
C. Autosomal recessive (Correct Answer)
D. Autosomal dominant
E. X-linked recessive
Explanation: ***Autosomal recessive***
- This presentation is classic for **Bernard-Soulier syndrome**, a rare **autosomal recessive** bleeding disorder characterized by a deficiency or defect in the **glycoprotein (GP) Ib/IX/V receptor complex** on platelets.
- The lack of ristocetin-induced platelet agglutination despite the addition of normal plasma indicates a **platelet function defect** rather than a deficiency of plasma factors like von Willebrand factor.
*X-linked dominant*
- X-linked dominant inheritance would typically show affected females and affected males, with male-to-male transmission not occurring, and all daughters of an affected father being affected.
- While bleeding disorders can be X-linked, the specific pattern of ristocetin non-agglutination points away from common X-linked dominant bleeding disorders, which are rare.
*Mitochondrial*
- Mitochondrial inheritance involves genes in the mitochondria and is passed down from the mother to all her children.
- Bleeding disorders are not typically associated with mitochondrial inheritance patterns.
*Autosomal dominant*
- Autosomal dominant disorders typically affect individuals in every generation, with a 50% chance of passing the condition to offspring.
- While **von Willebrand disease** is a common autosomal dominant bleeding disorder, the **ristocetin agglutination test result with normal plasma** effectively rules it out by pointing to a platelet receptor defect directly.
*X-linked recessive*
- **X-linked recessive** disorders like **hemophilia A** or **B** primarily affect males, with carrier females usually asymptomatic.
- These conditions are characterized by deficiencies in specific clotting factors, which would manifest differently in clotting assays and would not typically present with the specific ristocetin aggregation abnormality seen here.
Question 283: A 25-year-old man is brought to the emergency department by ambulance after a motor vehicle accident. His car was rear-ended by a drunk driver while he was stopped at a traffic light. At the scene, he was noted to have multiple small lacerations over his upper extremities from broken glass. He has otherwise been healthy, does not smoke, and drinks 5 beers per night. He notes that he recently started trying out a vegan diet and moved to an apartment located in a historic neighborhood that was built in the 1870s. Physical exam reveals several small lacerations on his arms bilaterally but is otherwise unremarkable. A complete blood workup is sent and some of the notable findings are shown below:
Hemoglobin: 12.1 g/dL (normal: 13.5-17.5 g/dL)
Platelet count: 261,000/mm^3 (normal: 150,000-400,000/mm^3)
Mean corpuscular volume: 74 µm^3 (normal: 80-100 µm^3)
Further testing using serum hemoglobin electrophoresis reveals:
Hemoglobin A1 92% (normal 95-98%)
Hemoglobin A2: 6% (normal: 1.5-3.1%)
Which of the following cell morphologies would most likely be seen on blood smear in this patient?
A. Spherocytes
B. Schistocytes
C. Codocytes (Correct Answer)
D. Megaloblasts
E. All cells appear normal
Explanation: ***Codocytes***
- Elevated Hb A2 (6%), low MCV (74), and mild anemia are classic findings of **beta-thalassemia minor (beta-thalassemia trait)**, which is associated with the presence of **codocytes (target cells)** on blood smear.
- **Codocytes** result from an imbalance in the globin chains causing excess membrane relative to hemoglobin content, which then folds in on itself, giving the cell a "target-like" appearance.
- The elevated **HbA2 >3.5%** is diagnostic of beta-thalassemia trait, as the beta chain deficiency leads to compensatory increase in delta chain production (HbA2 = α2δ2).
*Spherocytes*
- **Spherocytes** are small, round red blood cells lacking central pallor, characteristic of **hereditary spherocytosis** or **autoimmune hemolytic anemia**.
- These conditions typically present with hemolytic anemia (elevated bilirubin, reticulocytosis, positive Coombs test), which are not present in this patient.
- The elevated HbA2 confirms beta-thalassemia trait, not a hemolytic process.
*Schistocytes*
- **Schistocytes** are fragmented red blood cells that indicate **microangiopathic hemolytic anemia** (TTP, HUS, DIC) or mechanical red cell destruction.
- There are no signs of hemolysis, thrombocytopenia, or organ dysfunction in this patient.
*Megaloblasts*
- **Megaloblasts** are large, immature red blood cell precursors seen in bone marrow in **megaloblastic anemia**, often due to **vitamin B12** or **folate deficiency**.
- This patient presents with **microcytic anemia** (MCV 74), not macrocytic anemia, ruling out megaloblastic causes.
*All cells appear normal*
- The patient has **low hemoglobin** and **low MCV**, indicating microcytic anemia, which rules out a normal blood smear appearance.
- The elevated HbA2 confirms beta-thalassemia trait with expected target cells on blood smear.
Question 284: A 64-year-old man comes to the physician because of fatigue and decreased urinary frequency for 6 months. His pulse is 86/min and blood pressure is 150/90 mm Hg. Examination shows 1+ edema on bilateral ankles. His serum creatinine is 2 mg/dL and blood urea nitrogen is 28 mg/dL. Urinalysis shows proteinuria. A photomicrograph of a biopsy specimen from the patient's kidney is shown. Which of the following is the most likely explanation for the patient’s biopsy findings?
A. Amyloidosis
B. Recurrent kidney infections
C. Chronic hyperglycemia (Correct Answer)
D. Systemic lupus erythematosus
E. HIV infection
Explanation: ***Chronic hyperglycemia***
- Chronic hyperglycemia, as seen in **diabetes mellitus**, causes **diabetic nephropathy**, which is characterized by diffuse **glomerulosclerosis** and **nodular glomerulosclerosis** (Kimmelstiel-Wilson lesions) on biopsy.
- The patient's symptoms (fatigue, decreased urinary frequency, edema), elevated **creatinine and BUN**, and **proteinuria** are all consistent with chronic kidney disease secondary to diabetes.
*Amyloidosis*
- **Amyloidosis** would show characteristic **apple-green birefringence** under polarized light after Congo red staining, which is not described.
- While amyloidosis can cause proteinuria and kidney failure, the biopsy findings of diffuse and nodular glomerulosclerosis are classic for diabetic nephropathy.
*Recurrent kidney infections*
- Recurrent kidney infections (pyelonephritis) typically lead to **tubulointerstitial scarring** and inflammation, not predominantly glomerular changes.
- While they can cause chronic kidney disease, the biopsy would show signs of infection and interstitial damage rather than glomerulosclerosis.
*Systemic lupus erythematosus*
- Lupus nephritis manifests with various patterns of **glomerulonephritis**, including proliferative and membranous forms, often with **immune complex deposits**.
- The biopsy findings described (diffuse and nodular glomerulosclerosis) are not characteristic of lupus nephritis.
*HIV infection*
- HIV-associated nephropathy (HIVAN) typically presents as **focal segmental glomerulosclerosis (FSGS)**, often with collapsing glomerulopathy.
- While HIV infection can lead to kidney disease, the characteristic nodular and diffuse glomerulosclerosis seen in this patient points away from HIVAN.
Question 285: A 12-year-old boy is brought to an outpatient clinic by his mother, who noticed that her son’s urine has been dark for the past 4 days. She initially attributed this to inadequate hydration, so she monitored her son’s fluid intake and encouraged him to drink more water. However, she noticed that the color of the urine kept getting darker until it began to resemble cola. The boy’s medical history is significant for a sore throat approx. 2 weeks ago, which resolved without medication or treatment. The boy has also been complaining of pain in his ankles, which he first noticed shortly after soccer practice 1 week ago. He has had no pain during urination or urethral discharge, however, and does not have any history of previous episodes of cola-colored urine or passage of blood in the urine. However, the boy has been experiencing intermittent episodes of abdominal pain for the past 3 days. The boy also has wheals on his torso, legs, and buttocks, which his mother attributes to seasonal allergies. Physical examination reveals an alert child who is not in obvious distress but who has a mild conjunctival pallor. Vital signs include: respiratory rate is 22/min, temperature is 36.7°C (98.0°F), and blood pressure is 130/90 mm Hg. Examination of the musculoskeletal system reveals multiple skin lesions (see image). Which of the following laboratory findings is most likely associated with this patient’s clinical presentation?
A. Elevated level of serum IgA (Correct Answer)
B. Elevated IgM-IgG immune complex rheumatoid factor
C. 24-hour urinary protein of more than 4 g
D. Elevated levels of serum IgG and C3 protein
E. Low C-reactive protein level
Explanation: ***Elevated level of serum IgA***
- The patient's presentation with **cola-colored urine** (hematuria), recent **sore throat**, **abdominal pain**, **arthralgia**, and a **purpuric rash** is highly suggestive of **Henoch-Schönlein purpura (HSP)**, now known as **IgA vasculitis**.
- HSP is characterized by **IgA-dominant immune complex deposition** in small vessels, leading to **elevated serum IgA levels** in 50-90% of cases.
- This is the most specific laboratory finding for this patient's clinical presentation.
*Elevated IgM-IgG immune complex rheumatoid factor*
- **Rheumatoid factor (RF)** is an autoantibody (typically IgM against IgG Fc) primarily associated with **rheumatoid arthritis** and other rheumatologic conditions.
- This patient's symptoms are more consistent with a **small vessel vasculitis** (HSP) rather than rheumatoid arthritis.
- The arthralgia in HSP is due to vasculitis, not synovitis.
*24-hour urinary protein of more than 4 g*
- A **24-hour urinary protein excretion** exceeding 3.5 g/day defines **nephrotic-range proteinuria**.
- While HSP can involve the kidneys (**IgA nephropathy**), the typical presentation features **hematuria with mild-to-moderate proteinuria**.
- Nephrotic-range proteinuria (>4 g/24hr) is uncommon in HSP and less characteristic than elevated serum IgA.
*Elevated levels of serum IgG and C3 protein*
- Elevated serum IgG is a nonspecific marker of immune activation and is not characteristic of HSP.
- **Complement levels (C3, C4) are typically normal in HSP**, as it is not a complement-mediated vasculitis.
- Low C3 levels would suggest **post-streptococcal glomerulonephritis** (low C3, normal C4) or **lupus nephritis** (low C3 and C4), not HSP.
*Low C-reactive protein level*
- **C-reactive protein (CRP)** is an **acute phase reactant** that is typically **elevated** during inflammatory and vasculitic processes, including HSP.
- A **low CRP level** would be inconsistent with the active systemic inflammation indicated by this patient's symptoms (arthralgia, abdominal pain, rash, and renal involvement).
Question 286: A 55-year-old male presents to his primary care physician complaining of right hip pain for the past eight months. He also reports progressive loss of hearing over the same time period. Radiographic imaging reveals multiple areas of expanded bony cortices and coarsened trabeculae in his right hip and skull. Laboratory analysis reveals an isolated elevation in alkaline phosphatase with normal levels of serum calcium and phosphate. Which of the following histologic findings is most likely to be seen if one of the lesions were biopsied?
A. Mature lamellar bone with collagen fibers arranged in lamellae
B. Immature woven bone with collagen fibers arranged irregularly (Correct Answer)
C. Chondroblasts and chondrocytes forming a cartilaginous matrix
D. Sheets of monotonous round blue cells
E. Large pleomorphic cells with numerous atypical mitotic figures and “lacey” osteoid formation
Explanation: ***Immature woven bone with collagen fibers arranged irregularly***
- The clinical presentation (hip pain, hearing loss, elevated **alkaline phosphatase**, and radiographic findings of expanded cortices and coarsened trabeculae) is highly suggestive of **Paget's disease of bone** (osteitis deformans).
- Biopsy of a Pagetic lesion classically shows a **mosaic pattern of woven and lamellar bone**, with prominent cement lines, reflecting the chaotic and rapid bone turnover. **Immature woven bone** is a hallmark.
*Mature lamellar bone with collagen fibers arranged in lamellae*
- This describes normal healthy adult bone and would not be seen in a condition characterized by **disordered bone remodeling** such as Paget's disease.
- **Lamellar bone** is the characteristic type of bone found in healthy adults, where collagen fibers are organized in parallel layers.
*Chondroblasts and chondrocytes forming a cartilaginous matrix*
- This describes **cartilage**, which is not the primary tissue affected in Paget's disease within bone lesions.
- This finding would be typical of cartilaginous tumors or normal epiphyseal plates, not a bone remodeling disorder.
*Sheets of monotonous round blue cells*
- This description is characteristic of certain **hematologic malignancies** or small round cell tumors, such as lymphomas, Ewing sarcoma, or neuroblastoma.
- These findings are not associated with Paget's disease, which is a disorder of bone remodeling.
*Large pleomorphic cells with numerous atypical mitotic figures and “lacey” osteoid formation*
- This describes **osteosarcoma**, a primary malignant bone tumor, which can be a rare complication of long-standing Paget's disease but is not the primary histological finding of Paget's disease itself.
- While the patient has Paget's, the question asks for the most likely finding of the lesion itself, not a potential malignant transformation.
Question 287: A 57-year-old man presents to his primary care physician with a 2-month history of right upper and lower extremity weakness. He noticed the weakness when he started falling far more frequently while running errands. Since then, he has had increasing difficulty with walking and lifting objects. His past medical history is significant only for well-controlled hypertension, but he says that some members of his family have had musculoskeletal problems. His right upper extremity shows forearm atrophy and depressed reflexes while his right lower extremity is hypertonic with a positive Babinski sign. Which of the following is most likely associated with the cause of this patient's symptoms?
A. HLA-DR2 haplotype
B. Mutation in SOD1 (Correct Answer)
C. Viral infection
D. HLA-B8 haplotype
E. Mutation in SMN1
Explanation: ***Mutation in SOD1***
- The patient exhibits features of both **upper motor neuron (UMN)** and **lower motor neuron (LMN)** lesions, specifically **forearm atrophy** and depressed reflexes (LMN) alongside **hypertonicity** and a **positive Babinski sign** (UMN). This combination is characteristic of **amyotrophic lateral sclerosis (ALS)**.
- Mutations in the **superoxide dismutase 1 (SOD1)** gene are responsible for approximately 20% of familial ALS cases, aligning with the patient's report of "some members of his family have had musculoskeletal problems."
*HLA-DR2 haplotype*
- The **HLA-DR2 haplotype** is strongly associated with **multiple sclerosis (MS)**, an autoimmune demyelinating disease.
- While MS can cause UMN symptoms, it typically does not present with the pronounced LMN signs like **atrophy** and **depressed reflexes** seen in this patient.
*Viral infection*
- **Viral infections** can trigger various neurological conditions, such as **Guillain-Barré syndrome** (GBS) which causes demyelination of peripheral nerves.
- GBS primarily results in **ascending motor weakness** and **areflexia** (LMN signs), but it does not cause UMN signs like hypertonicity or a positive Babinski sign.
*HLA-B8 haplotype*
- The **HLA-B8 haplotype** is associated with several autoimmune diseases, including **myasthenia gravis** and **celiac disease**.
- While myasthenia gravis causes **muscle weakness**, it is characterized by **fluctuating weakness** that worsens with activity and improves with rest, affecting specific muscle groups, unlike the progressive UMN and LMN involvement seen here.
*Mutation in SMN1*
- A **mutation in the SMN1 gene** is the primary cause of **spinal muscular atrophy (SMA)**, a genetic disorder.
- SMA specifically leads to the death of **lower motor neurons** in the spinal cord, resulting in exclusively LMN signs such as **muscle weakness** and **atrophy**, without any UMN involvement (e.g., hypertonicity or Babinski sign).
Question 288: A 3-year-old girl is brought to her pediatrician because of a nosebleed that will not stop. Her parents say that she started having a nosebleed about 1 hour prior to presentation. Since then they have not been able to stop the bleeding. Her past medical history is remarkable for asthma, and she has a cousin who has been diagnosed with hemophilia. Physical exam reveals diffuse petechiae and purpura. A panel of bleeding tests are obtained with the following results:
Bleeding time: 11 minutes
Prothrombin time: 14 seconds
Partial thromboplastin time: 32 seconds
Platelet count: 195,000/mm^3
Peripheral blood smear shows normal cell morphology. Which of the following characteristics is most likely true about this patient?
A. Mutation in glycoprotein IIb/IIIa (Correct Answer)
B. Mutation in glycoprotein Ib
C. Production of anti platelet antibodies
D. Production of antibodies against ADAMTS13
E. Decreased levels of von Willebrand factor
Explanation: ***Mutation in glycoprotein IIb/IIIa***
- The patient's symptoms (nosebleed, petechiae, purpura) and laboratory findings (prolonged **bleeding time**, normal platelet count, normal PT/PTT) are characteristic of **Glanzmann's thrombasthenia**, which is caused by a qualitative defect in **glycoprotein IIb/IIIa**.
- **Glycoprotein IIb/IIIa** is crucial for platelet aggregation, and a mutation in this protein prevents platelets from forming a stable clot.
*Mutation in glycoprotein Ib*
- A mutation in **glycoprotein Ib** leads to **Bernard-Soulier syndrome**, characterized by prolonged bleeding time, normal platelet count, and **abnormally large platelets** on peripheral smear, which are not seen here.
- Glycoprotein Ib is involved in platelet adhesion to von Willebrand factor, not aggregation.
*Production of anti platelet antibodies*
- This describes **Immune Thrombocytopenic Purpura (ITP)**, which would typically present with a **low platelet count**, not a normal count as seen in this patient.
- While ITP can cause petechiae and bleeding, the normal platelet count rules it out.
*Production of antibodies against ADAMTS13*
- This condition is **Thrombotic Thrombocytopenic Purpura (TTP)**, characterized by a **low platelet count**, microangiopathic hemolytic anemia, renal failure, neurological symptoms, and fever, none of which fully align with this patient's presentation.
- TTP usually has significant **thrombocytopenia** and normal bleeding time, despite symptoms of bleeding.
*Decreased levels of von Willebrand factor*
- **Von Willebrand disease (vWD)** would typically show a **prolonged bleeding time** and, depending on the type, may also have a prolonged PTT (due to low factor VIII).
- However, the diffuse petechiae and purpura with a normal platelet count and normal PT/PTT point more strongly towards a platelet function defect rather than a primary coagulation factor deficiency or vWD.
Question 289: An 8-year-old boy is brought to the physician by his parents because of fever for 3 days. During the period, he has had fatigue, severe burning with urination, and increased urination. The mother reports that his urine has red streaks and a “strange” odor. He has taken acetaminophen twice a day for the past two days with no improvement in his symptoms. He has had multiple ear infections in the past but has been healthy in the past year. His immunizations are up-to-date. He appears uncomfortable. His temperature is 39°C (102.2°F). Examination shows right-sided costovertebral angle tenderness. Laboratory studies show a leukocyte count of 16,000/cm3 and an erythrocyte sedimentation rate of 40 mm/hr. Urine dipstick shows leukocyte esterase and nitrites. Urinalysis shows:
Blood 2+
Protein 2+
WBC 24/hpf
RBC 50/hpf
RBC casts none
WBC casts numerous
Granular casts none
Urine cultures are sent to the laboratory. Damage to which of the following structures is the most likely cause of this patient's hematuria?
A. Renal tubules
B. Urethral epithelium
C. Mucosa of the bladder
D. Renal papilla
E. Renal interstitium (Correct Answer)
Explanation: ***Renal interstitium***
- This patient has **acute pyelonephritis**, indicated by fever, **costovertebral angle tenderness**, elevated inflammatory markers (WBC 16,000, ESR 40), positive leukocyte esterase and nitrites, and most importantly, **WBC casts** in the urine.
- Acute pyelonephritis is characterized by **bacterial infection of the renal parenchyma**, primarily affecting the **renal interstitium** (the tissue between tubules containing blood vessels, inflammatory cells, and connective tissue).
- The **hematuria** (RBC 50/hpf, Blood 2+) results from **inflammatory damage to interstitial capillaries** and disruption of the normal tissue architecture due to bacterial invasion and immune response.
- **WBC casts** form when WBCs from the inflamed interstitium enter the tubular lumen and aggregate with Tamm-Horsfall protein, confirming upper urinary tract (kidney) infection rather than simple cystitis.
*Renal papilla*
- **Papillary necrosis** can cause severe hematuria but typically occurs in specific settings: diabetes mellitus, sickle cell disease, chronic analgesic abuse (NSAIDs), or severe obstruction—none of which are present in this otherwise healthy child.
- While severe pyelonephritis can rarely lead to papillary necrosis, the clinical presentation here is consistent with **uncomplicated acute pyelonephritis** where interstitial inflammation is the primary pathology.
*Renal tubules*
- **Acute tubular necrosis (ATN)** presents with acute kidney injury, elevated creatinine, and **muddy brown granular casts**, which are not seen here.
- While tubular cells may be affected secondarily in pyelonephritis, the primary site of damage is the **interstitium**, not the tubules themselves.
*Urethral epithelium*
- **Urethritis** causes dysuria and urethral discharge but does not produce **fever**, **CVA tenderness**, or **WBC casts**, which indicate kidney involvement.
- Urethral inflammation would not explain the systemic inflammatory response or the casts originating from the kidney.
*Mucosa of the bladder*
- **Cystitis** (bladder infection) causes dysuria, frequency, and urgency, but typically lacks **high fever** and **CVA tenderness**, which are hallmarks of kidney infection.
- While cystitis can cause hematuria, the presence of **WBC casts** definitively localizes the infection to the kidney (renal parenchyma/interstitium), not the bladder.
Question 290: A 42-year-old woman comes to the physician because of a 10-month history of joint pain and stiffness in her wrists and fingers. The symptoms are worse in the morning and improve with activity. Physical examination shows swelling and warmth over the MCP and wrist joints in both hands. An x-ray of the hands is shown. Synovial biopsy from an affected joint would most likely show which of the following?
A. Proliferation of granulation tissue (Correct Answer)
B. Noninflammatory superficial fibrin deposits
C. Monosodium urate crystals
D. Calcium pyrophosphate crystals
E. Noncaseating granulomas
Explanation: ***Proliferation of granulation tissue***
- The patient's presentation of symmetric polyarthritis, morning stiffness, and involvement of the **MCP and wrist joints**, with improvement with activity, is highly suggestive of **rheumatoid arthritis**.
- In rheumatoid arthritis, the inflamed synovium undergoes marked proliferation, forming a highly vascularized, destructive tissue known as **pannus**, which is characterized by the proliferation of granulation tissue.
*Noninflammatory superficial fibrin deposits*
- This finding is not characteristic of the progressive inflammatory and destructive process seen in rheumatoid arthritis, which involves significant cellular infiltration and tissue remodeling.
- While fibrin may be present, its deposition is typically part of an inflammatory response, and a superficial, noninflammatory state would not explain the joint pathology described.
*Monosodium urate crystals*
- These crystals are the hallmark of **gout**, a condition characterized by acute, painful attacks typically affecting a single joint initially, often the great toe, and not the diffuse, symmetrical polyarthritis seen here.
- Gout flares are typically very severe and episodic, without the chronic morning stiffness and gradual improvement with activity typical of rheumatoid arthritis.
*Calcium pyrophosphate crystals*
- These crystals are associated with **calcium pyrophosphate deposition disease (CPPD)**, also known as pseudogout.
- Pseudogout typically affects larger joints (e.g., knee, wrist) and can mimic gout or osteoarthritis, but does not present with the characteristic symmetric pattern and destructive pannus formation of rheumatoid arthritis.
*Noncaseating granulomas*
- **Noncaseating granulomas** are the histological hallmark of **sarcoidosis**, a systemic inflammatory disease that can affect joints in an acute or chronic arthropathy.
- While sarcoidosis can cause arthritis, the clinical description of chronic inflammatory polyarthritis with specific joint involvement and progression is more consistent with rheumatoid arthritis, and granulomas are not a typical feature of rheumatoid synovium.
