A 7-year-old girl presents to a new pediatrician with fever, shortness of breath, and productive cough. She had similar symptoms a few weeks ago. The girl was born at 39 weeks gestation via spontaneous vaginal delivery. She is up to date on all vaccines and is meeting all developmental milestones. A further review of her history reveals seizures, upper respiratory infections, and cellulitis. On physical examination, the patient is pale with white-blonde hair and pale blue eyes. Which of the following would you expect to see on a peripheral blood smear for this patient?
Q302
A 2-year-old girl with a history of SS-hemoglobin is brought to her pediatrician by her mother, who noted an abdominal mass. On exam, the girl's spleen is palpably enlarged, and her palms and conjunctiva are noted to be extremely pale. Serum haptoglobin levels are decreased. Which of the following is the most likely cause of this patient's symptoms?
Q303
Several weeks following a kidney transplantation, a 50-year-old Caucasian female presents for evaluation of the transplanted organ. Biopsy shows inflammation involving the endothelial cells of the kidney vasculature and the presence of mononuclear cells in the interstitium. Which cells are most likely responsible for this presentation?
Q304
A 67-year-old man comes to the emergency department for evaluation of progressively worsening edema and decreased urine output over the past few days. He has a history of chronic sinus infections and was hospitalized last year for a suspected pneumonia with hemoptysis. Physical exam shows bilateral pitting edema of the lower extremities. Serum studies show a creatinine of 3.4 mg/dL and blood urea nitrogen of 35 mg/dL. Urine dipstick shows 3+ blood. A kidney biopsy is performed and light microscopy shows crescent-shaped glomeruli. Immunofluorescent microscopy of the tissue sample is most likely to show which of the following findings?
Q305
A 9-year-old boy is brought to the physician by his parents because of right-sided shoulder pain for 1 day. He has not had chills or sweating. Over the past year, he was treated twice in the emergency department for painful swelling of his hands and feet. He emigrated with his family from Kenya 2 years ago. His temperature is 37.4°C (99.3°F), pulse is 96/min, and blood pressure is 123/82 mm Hg. Physical examination shows no tenderness, erythema, or joint swelling of the shoulder. Laboratory studies show:
Hemoglobin 7 g/dL
Mean corpuscular volume 88 μm
Reticulocyte count 9%
Leukocyte count 12,000/mm3
A peripheral blood smear is most likely to show which of the following abnormalities?
Q306
An 8-year-old boy presents to the emergency department with puffy eyes. The patient’s parents noticed that his eyes were very puffy this morning thus prompting his presentation. They state their son has always been very healthy and other than a rash acquired from wrestling treated with a topical antibiotic has been very healthy. His temperature is 98.3°F (36.8°C), blood pressure is 125/85 mmHg, pulse is 89/min, respirations are 18/min, and oxygen saturation is 99% on room air. Physical exam is notable for periorbital edema but is otherwise unremarkable. Urinalysis is notable for red blood cells and an amber urine sample. Which of the following is the most likely etiology of this patient’s symptoms?
Q307
An 11-year-old African American boy is brought to your office by his parents with a 1-day history of severe left hip pain. It is too painful for him to walk without support. He took ibuprofen, which brought no relief. He has had no chills or sweats. Similar painful episodes in the past required multiple hospitalizations. He returned from a trip to Kenya with his family 2 months ago. His vaccinations are up-to-date. His temperature is 38°C (100.4° F), pulse is 100/min, blood pressure is 120/80 mm Hg. Physical examination shows pale conjunctivae. The abdomen is soft with no organomegaly. Passive movement of the hip causes severe pain. There is tenderness on palpation, but no swelling, warmth, or erythema of the hip. His laboratory studies show a hematocrit of 25% and leukocyte count of 14 000/mm3. A peripheral blood smear would most likely show which of the following?
Q308
An 18-month-old boy is presented to the emergency department by his parents due to swelling in his right knee after playing in the park. His parents say there was no obvious injury. After questioning, the mother says that an uncle of hers had similar problems. The vital signs include heart rate 146/min, respiratory rate 26/min, temperature 37.1°C (98.8°F) and blood pressure 90/52 mm Hg. On physical examination, the swelling of the right knee is evident. The rest of the physical findings are unremarkable. The ultrasound is compatible with the hemarthrosis of the right knee. The complete blood count (CBC) results are as follows:
Hemoglobin 12.2 g/dL
Hematocrit 36%
Leukocyte count 7,300/mm3
Neutrophils 45%
Bands 3%
Eosinophils 1%
Basophils 0%
Lymphocytes 44%
Monocytes 2%
Platelet count 200,000/mm³
The coagulation test results are as follows:
Partial thromboplastin time (activated) 52.0 s
Prothrombin time 14.0 s
Reticulocyte count 1.2%
Thrombin time < 2 seconds deviation from control
What is the most likely diagnosis?
Q309
A 52-year-old man comes to the physician because of malaise and dark urine for the past 5 days. He has also had recurrent episodes of sinus congestion, productive cough, and fever for 3 months. Additionally, he has noticed a rash on his arms and feet. He has seasonal allergic conjunctivitis treated with ketotifen eye drops. Vital signs are within normal limits. Examination shows several erythematous and necrotic papules on his arms and feet. He has inflamed nasopharyngeal mucosa and a perforated nasal septum. The nasal bridge is collapsed. Laboratory studies show:
Hemoglobin 11.3 g/dL
Leukocyte count 12000/mm3
Platelet count 270,000/mm3
ESR 55 mm/hr
Serum
Urea nitrogen 28 mg/dL
Creatinine 2.9 mg/dL
Anti-DNA antibodies negative
Antineutrophil cytoplasmic antibodies positive
Urine
Protein 2+
Glucose negative
RBC 35–37/hpf
RBC casts numerous
Which of the following biopsy findings is most likely to be observed in this patient?
Q310
An 8-year-old boy is brought to the pediatric emergency department by his parents with a complaint of abdominal pain and diarrhea for the past week. He states that for the past two days, he has noticed blood in his stool. His parents note that they attended a neighbor’s barbecue last weekend, but otherwise have not eaten any new foods or changed their usual diet. The patient is admitted to the hospital unit for further work-up. The provider team finds that the patient’s blood is positive for Shiga-like toxin and notes the following lab values: creatinine of 4.2 mg/dL, platelet count of 50,000/mm^3, and hemoglobin of 6.0 g/dL. Which of the following additional lab findings would be consistent with the diagnosis?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 301: A 7-year-old girl presents to a new pediatrician with fever, shortness of breath, and productive cough. She had similar symptoms a few weeks ago. The girl was born at 39 weeks gestation via spontaneous vaginal delivery. She is up to date on all vaccines and is meeting all developmental milestones. A further review of her history reveals seizures, upper respiratory infections, and cellulitis. On physical examination, the patient is pale with white-blonde hair and pale blue eyes. Which of the following would you expect to see on a peripheral blood smear for this patient?
A. Polymorphonuclear leukocytes containing giant inclusion bodies (Correct Answer)
B. Predominance of band leukocytes
C. Downey cells
D. Stippled eosinophils
E. Significant basophil predominance
Explanation: ***Polymorphonuclear leukocytes containing giant inclusion bodies***
- This constellation of symptoms: **recurrent infections** (respiratory infections, cellulitis), **neurological abnormalities** (seizures), and **partial albinism** (pale skin, white-blonde hair, pale blue eyes) is characteristic of **Chédiak-Higashi syndrome**.
- **Chédiak-Higashi syndrome** is an autosomal recessive disorder characterized by defective lysosomal trafficking, leading to the formation of abnormally large **lysosomes** and **granules** in various cell types, including melanocytes, lymphocytes, and granulocytes. These giant granules are visible as **inclusion bodies** within polymorphonuclear leukocytes on a peripheral blood smear.
*Predominance of band leukocytes*
- A predominance of **band leukocytes** (immature neutrophils) indicates a **left shift**, which is commonly seen in acute bacterial infections and suggests the bone marrow is rapidly producing neutrophils.
- While this patient has infections, a left shift is a general response to infection and not a specific finding for Chédiak-Higashi syndrome, which primarily involves abnormal inclusion bodies.
*Downey cells*
- **Downey cells** are atypical lymphocytes, specifically activated cytotoxic T cells, classically associated with **infectious mononucleosis** caused by the Epstein-Barr virus (EBV).
- This patient's chronic and recurrent bacterial infections and characteristic albinism do not suggest infectious mononucleosis.
*Stippled eosinophils*
- **Stippled eosinophils** (basophilic stippling within eosinophils) are not a recognized abnormality or an indicator of any specific disease.
- While eosinophilia can occur in certain conditions (e.g., parasitic infections, allergic reactions), the presence of "stippled" eosinophils is not a known hematologic feature.
*Significant basophil predominance*
- A significant basophil predominance, or **basophilia**, can be seen in conditions like **myeloproliferative neoplasms** (e.g., chronic myeloid leukemia) or certain allergic reactions.
- This finding is not consistent with the clinical presentation of recurrent infections, neurological issues, and albinism seen in this patient.
Question 302: A 2-year-old girl with a history of SS-hemoglobin is brought to her pediatrician by her mother, who noted an abdominal mass. On exam, the girl's spleen is palpably enlarged, and her palms and conjunctiva are noted to be extremely pale. Serum haptoglobin levels are decreased. Which of the following is the most likely cause of this patient's symptoms?
A. Intravascular hemolysis
B. Extravascular hemolysis (Correct Answer)
C. Hemolytic uremic syndrome
D. Complement-mediated hemolysis
E. Decreased red blood cell production
Explanation: ***Extravascular hemolysis***
- This patient presents with **anemia** (pale conjunctiva and palms) and an **enlarged spleen**, which are classic signs of **extravascular hemolysis**. **Sickle cell disease** is a condition known to cause chronic hemolysis through this mechanism, where damaged red blood cells are removed by the reticuloendothelial system, primarily in the spleen.
- In **extravascular hemolysis**, red blood cells are destroyed outside of the bloodstream by macrophages in the spleen, liver, and bone marrow. While this process releases less **free hemoglobin** into circulation than intravascular hemolysis, **chronic hemolysis in sickle cell disease still leads to decreased haptoglobin levels** due to ongoing red cell destruction and some degree of intravascular hemolysis.
- The **splenomegaly** in this young patient is characteristic, as the spleen becomes engorged with sequestered and destroyed sickled red blood cells before it undergoes autoinfarction in later childhood.
*Intravascular hemolysis*
- **Intravascular hemolysis** involves the destruction of red blood cells within the circulation, leading to the release of **free hemoglobin**.
- While sickle cell disease does have some intravascular component, the **primary mechanism is extravascular**, and the presence of **significant splenomegaly** with palpable abdominal mass points to splenic sequestration and extravascular destruction as the dominant process.
*Hemolytic uremic syndrome*
- **Hemolytic uremic syndrome (HUS)** is characterized by a triad of **microangiopathic hemolytic anemia**, **thrombocytopenia**, and **acute kidney injury**.
- While it involves hemolysis, the patient's presentation lacks **thrombocytopenia** and evidence of **renal failure**, making HUS less likely. Additionally, HUS is not typically associated with **sickle cell disease**.
*Complement-mediated hemolysis*
- **Complement-mediated hemolysis** is seen in conditions like **paroxysmal nocturnal hemoglobinuria (PNH)** or some autoimmune hemolytic anemias.
- This typically results in **intravascular hemolysis** due to complement activation on red cell surfaces. The patient's known diagnosis of **sickle cell disease** makes this mechanism less likely as the primary cause.
*Decreased red blood cell production*
- Conditions with **decreased red blood cell production**, such as **aplastic anemia** or **pure red cell aplasia**, would present with anemia but not typically with an **enlarged spleen** or evidence of significant red blood cell destruction.
- The patient's history of **SS-hemoglobin (sickle cell disease)** and **decreased haptoglobin** point towards a hemolytic process rather than bone marrow suppression as the primary cause of anemia.
Question 303: Several weeks following a kidney transplantation, a 50-year-old Caucasian female presents for evaluation of the transplanted organ. Biopsy shows inflammation involving the endothelial cells of the kidney vasculature and the presence of mononuclear cells in the interstitium. Which cells are most likely responsible for this presentation?
A. Recipient T-cells (Correct Answer)
B. Donor antibodies
C. Preformed recipient antibodies
D. Deposition of antibody immune complexes
E. Donor T-cells
Explanation: ***Recipient T-cells***
- The presence of **mononuclear cells in the interstitium** and inflammation of the **endothelial cells** several weeks post-transplantation is characteristic of **acute cellular rejection (ACR)**.
- ACR is primarily mediated by the recipient's **cytotoxic T-cells** recognizing donor major histocompatibility complex (MHC) molecules on graft cells.
*Donor antibodies*
- Donor antibodies are not responsible for rejection; rather, recipient antibodies (either preformed or newly formed) are implicated.
- The donor's immune system is suppressed or non-existent in the context of the transplanted organ itself after removal from the donor.
*Preformed recipient antibodies*
- While preformed recipient antibodies cause **hyperacute rejection**, which occurs minutes to hours after transplant, the presentation here is several weeks later.
- Hyperacute rejection involves widespread thrombosis and necrosis due to rapid antibody-mediated complement activation within the graft vasculature.
*Deposition of antibody immune complexes*
- Immune complex deposition typically causes a different pattern of injury (e.g., glomerulonephritis) and is not the primary mechanism of acute cellular rejection.
- This mechanism is more associated with certain autoimmune diseases or chronic transplant rejection, not the acute phase described.
*Donor T-cells*
- Donor T-cells would not be attacking the transplanted organ since it is *their own tissue*.
- Donor T-cells can cause **graft-versus-host disease (GVHD)** in bone marrow transplantation, where immunocompetent donor T-cells attack recipient tissues, but this is not applicable to solid organ transplantation.
Question 304: A 67-year-old man comes to the emergency department for evaluation of progressively worsening edema and decreased urine output over the past few days. He has a history of chronic sinus infections and was hospitalized last year for a suspected pneumonia with hemoptysis. Physical exam shows bilateral pitting edema of the lower extremities. Serum studies show a creatinine of 3.4 mg/dL and blood urea nitrogen of 35 mg/dL. Urine dipstick shows 3+ blood. A kidney biopsy is performed and light microscopy shows crescent-shaped glomeruli. Immunofluorescent microscopy of the tissue sample is most likely to show which of the following findings?
A. Subendothelial deposits
B. Mesangial deposits
C. Intramembranous deposits
D. No deposits (Correct Answer)
E. Subepithelial deposits
Explanation: ***No deposits***
- The presence of **crescentic glomeruli** on light microscopy and a history of chronic sinus infections and hemoptysis strongly suggest **Granulomatosis with Polyangiitis (GPA)**, a form of **pauci-immune glomerulonephritis**.
- In pauci-immune glomerulonephritis, immunofluorescence typically shows **scanty or no immune deposits** in the glomeruli.
*Subendothelial deposits*
- **Subendothelial deposits** are characteristic of conditions like **membranoproliferative glomerulonephritis** (types I and III) or **lupus nephritis**, which typically do not present with the described clinical picture of chronic upper respiratory issues and hemoptysis.
- These deposits would be associated with significant immune complex deposition, which contradicts the "pauci-immune" nature suggested by the clinical presentation.
*Mesangial deposits*
- **Mesangial deposits** are a hallmark of **IgA nephropathy** or early stages of lupus nephritis, where IgA or other immune complexes accumulate in the mesangium.
- While IgA nephropathy can cause hematuria, the crescentic glomerulonephritis and systemic features (sinusitis, hemoptysis) point away from isolated mesangial involvement as the primary pathology.
*Intramembranous deposits*
- **Intramembranous deposits** are typically seen in conditions like **dense deposit disease** (a complement-mediated glomerulonephritis) or some forms of cryoglobulinemic glomerulonephritis.
- These conditions usually have distinct clinical presentations and specific patterns of complement activation or cryoglobulinemia, which are not indicated in this case.
*Subepithelial deposits*
- **Subepithelial deposits** (e.g., "humps") are characteristic of **post-streptococcal glomerulonephritis** and are rich in C3 and IgG.
- While post-streptococcal glomerulonephritis can cause crescent formation, the patient's age, chronic sinus issues, and hemoptysis make GPA a more fitting diagnosis.
Question 305: A 9-year-old boy is brought to the physician by his parents because of right-sided shoulder pain for 1 day. He has not had chills or sweating. Over the past year, he was treated twice in the emergency department for painful swelling of his hands and feet. He emigrated with his family from Kenya 2 years ago. His temperature is 37.4°C (99.3°F), pulse is 96/min, and blood pressure is 123/82 mm Hg. Physical examination shows no tenderness, erythema, or joint swelling of the shoulder. Laboratory studies show:
Hemoglobin 7 g/dL
Mean corpuscular volume 88 μm
Reticulocyte count 9%
Leukocyte count 12,000/mm3
A peripheral blood smear is most likely to show which of the following abnormalities?
A. Ring-shaped inclusions in erythrocytes
B. Erythrocytes with no central pallor
C. Teardrop-shaped erythrocytes
D. Fragmentation of erythrocytes
E. Nuclear remnants in erythrocytes (Correct Answer)
Explanation: ***Nuclear remnants in erythrocytes***
- This patient's history of **recurrent painful swelling** of hands and feet, emigration from Kenya, and current shoulder pain, combined with **anemia** (hemoglobin 7 g/dL) and **elevated reticulocyte count (9%)**, strongly suggests **sickle cell disease**.
- Complications such as **vaso-occlusive crises** can cause bone pain. **Nuclear remnants (Howell-Jolly bodies)** in erythrocytes are characteristic of **functional asplenia**, a common complication of sickle cell disease due to splenic infarction.
*Ring-shaped inclusions in erythrocytes*
- **Ring-shaped inclusions** are primarily associated with parasitic infections like **malaria** (ring forms of *Plasmodium* parasites within red blood cells).
- While the patient is from Kenya, the clinical picture here is not typical for an acute malaria presentation (no fever/chills), and other findings point more strongly to sickle cell disease complications.
*Erythrocytes with no central pallor*
- **Erythrocytes with no central pallor** (spherocytes) are characteristic of **hereditary spherocytosis** or **autoimmune hemolytic anemia**.
- While both can cause anemia and an elevated reticulocyte count, the history of recurrent painful swelling of hands and feet strongly points away from these disorders.
*Teardrop-shaped erythrocytes*
- **Teardrop-shaped erythrocytes (dacryocytes)** are typically seen in **myelofibrosis** and other myeloproliferative neoplasms, or severe marrow infiltration.
- This finding is not consistent with the clinical presentation of sickle cell disease.
*Fragmentation of erythrocytes*
- **Fragmentation of erythrocytes (schistocytes)** indicates **microangiopathic hemolytic anemia (MAHA)**, seen in conditions like thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), or disseminated intravascular coagulation (DIC).
- While sickle cell crises can involve microvascular occlusion, the primary red cell abnormality in sickle cell disease isn't schistocyte formation as a hallmark feature.
Question 306: An 8-year-old boy presents to the emergency department with puffy eyes. The patient’s parents noticed that his eyes were very puffy this morning thus prompting his presentation. They state their son has always been very healthy and other than a rash acquired from wrestling treated with a topical antibiotic has been very healthy. His temperature is 98.3°F (36.8°C), blood pressure is 125/85 mmHg, pulse is 89/min, respirations are 18/min, and oxygen saturation is 99% on room air. Physical exam is notable for periorbital edema but is otherwise unremarkable. Urinalysis is notable for red blood cells and an amber urine sample. Which of the following is the most likely etiology of this patient’s symptoms?
A. Deposition of circulating immune complexes (Correct Answer)
B. Increased glomerular permeability to protein only
C. IgE-mediated degranulation
D. IgA-mediated vasculitis
E. Autoimmune type IV collagen destruction
Explanation: ***Deposition of circulating immune complexes***
- The patient's symptoms, including **periorbital edema**, **hypertension**, and **hematuria** with a history of a **recent skin infection (wrestling rash)**, are classic for **post-streptococcal glomerulonephritis (PSGN)**.
- PSGN is caused by the deposition of **immune complexes** (antibodies bound to streptococcal antigens) in the glomeruli, leading to inflammation and damage.
*Increased glomerular permeability to protein only*
- This describes **nephrotic syndrome**, which is primarily characterized by **massive proteinuria** and severe edema, but typically **lacks hematuria** and significant hypertension.
- While there is edema, the presence of **red blood cells in the urine** points away from isolated protein permeability.
*IgE-mediated degranulation*
- This mechanism is characteristic of immediate type I hypersensitivity reactions, such as **allergic reactions** (e.g., anaphylaxis, urticaria).
- While it can cause angioedema, it does not typically lead to the **hematuria** and **hypertension** seen in this patient.
*IgA-mediated vasculitis*
- This describes **Henoch-Schönlein Purpura (HSP)**, which presents with a classic triad of palpable purpura, abdominal pain, and arthralgia, along with renal involvement **(IgA nephropathy)**.
- While HSP can cause hematuria, the absence of the characteristic **purpuric rash** and other systemic symptoms makes it less likely than PSGN in this context.
*Autoimmune type IV collagen destruction*
- This mechanism is associated with conditions like **Goodpasture syndrome**, where antibodies target the **alpha-3 chain of type IV collagen** in the glomerular and alveolar basement membranes.
- Goodpasture syndrome typically presents with **rapidly progressive glomerulonephritis** and often **pulmonary hemorrhage**, which are not indicated in this case.
Question 307: An 11-year-old African American boy is brought to your office by his parents with a 1-day history of severe left hip pain. It is too painful for him to walk without support. He took ibuprofen, which brought no relief. He has had no chills or sweats. Similar painful episodes in the past required multiple hospitalizations. He returned from a trip to Kenya with his family 2 months ago. His vaccinations are up-to-date. His temperature is 38°C (100.4° F), pulse is 100/min, blood pressure is 120/80 mm Hg. Physical examination shows pale conjunctivae. The abdomen is soft with no organomegaly. Passive movement of the hip causes severe pain. There is tenderness on palpation, but no swelling, warmth, or erythema of the hip. His laboratory studies show a hematocrit of 25% and leukocyte count of 14 000/mm3. A peripheral blood smear would most likely show which of the following?
A. Howell-Jolly bodies (Correct Answer)
B. Decreased number of reticulocytes
C. Trophozoites
D. Decreased number of thrombocytes
E. Gram-negative bacilli
Explanation: ***Howell-Jolly bodies***
- The patient's history of recurrent pain, African American ethnicity, and profound anemia (hematocrit 25%) are highly suggestive of **sickle cell disease**.
- Howell-Jolly bodies are **nuclear remnants** in red blood cells, typically removed by the spleen. Their presence indicates **functional asplenia**, which is common in sickle cell disease due to splenic auto-infarction.
*Decreased number of reticulocytes*
- This patient is experiencing a **painful vaso-occlusive crisis** and significant anemia, which usually stimulates increased erythropoiesis.
- A decreased reticulocyte count would suggest **aplastic crisis** (e.g., due to parvovirus B19), which is a possible complication but less likely the primary finding in an active crisis with marked anemia.
*Trophozoites*
- Trophozoites on a peripheral blood smear are characteristic of **malaria**, which is a consideration given his recent travel to Kenya.
- However, the history of **recurrent painful episodes** since childhood points more strongly to an underlying chronic condition like sickle cell disease, and malaria would typically present with cyclic fevers, chills, and sweats, which are absent here.
*Decreased number of thrombocytes*
- A decreased number of thrombocytes (thrombocytopenia) is not a typical finding in an uncomplicated sickle cell crisis.
- While possible in severe illness or specific complications, the presenting symptoms do not specifically point to a primary platelet disorder.
*Gram-negative bacilli*
- The presence of Gram-negative bacilli on a peripheral blood smear would indicate **bacteremia** or **sepsis**.
- While patients with sickle cell disease are at increased risk of infection, especially encapsulated bacteria due to functional asplenia, the primary diagnostic finding in the context of recurrent pain and anemia would be related to the underlying sickle cell pathology rather than an immediate infectious agent in this scenario.
Question 308: An 18-month-old boy is presented to the emergency department by his parents due to swelling in his right knee after playing in the park. His parents say there was no obvious injury. After questioning, the mother says that an uncle of hers had similar problems. The vital signs include heart rate 146/min, respiratory rate 26/min, temperature 37.1°C (98.8°F) and blood pressure 90/52 mm Hg. On physical examination, the swelling of the right knee is evident. The rest of the physical findings are unremarkable. The ultrasound is compatible with the hemarthrosis of the right knee. The complete blood count (CBC) results are as follows:
Hemoglobin 12.2 g/dL
Hematocrit 36%
Leukocyte count 7,300/mm3
Neutrophils 45%
Bands 3%
Eosinophils 1%
Basophils 0%
Lymphocytes 44%
Monocytes 2%
Platelet count 200,000/mm³
The coagulation test results are as follows:
Partial thromboplastin time (activated) 52.0 s
Prothrombin time 14.0 s
Reticulocyte count 1.2%
Thrombin time < 2 seconds deviation from control
What is the most likely diagnosis?
A. Bernard-Soulier disease
B. Hemophilia A (Correct Answer)
C. Von Willebrand disease
D. Marfan syndrome
E. Ehlers-Danlos syndrome
Explanation: ***Hemophilia A***
- The patient presents with **hemarthrosis** (joint bleeding) after minor trauma, which is characteristic of hemophilia. The **prolonged activated partial thromboplastin time (aPTT)** indicates an intrinsic pathway coagulation disorder.
- The family history of a male uncle having "similar problems" suggests an **X-linked recessive inheritance pattern**, which is classic for hemophilia A due to factor VIII deficiency.
*Bernard-Soulier disease*
- This is a **platelet function disorder** characterized by **giant platelets** and **thrombocytopenia**, none of which are observed in the patient's CBC.
- It would typically present with **mucocutaneous bleeding** (e.g., epistaxis, petechiae) rather than hemarthrosis alone, and coagulation times (aPTT, PT) would be normal.
*Von Willebrand disease*
- While it can manifest with bleeding, it usually causes **mucocutaneous bleeding** and **menorrhagia**, rather than spontaneous deep joint bleeds.
- Type 1 von Willebrand disease typically has a **normal or slightly prolonged aPTT**, and the bleeding tends to be less severe than in hemophilia A.
*Marfan syndrome*
- This is a **connective tissue disorder** affecting the skeletal, ocular, and cardiovascular systems.
- It does not primarily cause coagulation defects or hemarthrosis, and clinical features would include **tall stature**, **long limbs** (arachnodactyly), and **lens dislocation**.
*Ehlers-Danlos syndrome*
- This is another **connective tissue disorder** characterized by **skin hyperextensibility**, **joint hypermobility**, and tissue fragility.
- While patients can have easy bruising and some bleeding tendencies due to fragile vessels, it does not typically cause severe hemarthrosis with a prolonged aPTT in the absence of trauma, and it's not a primary coagulation factor deficiency.
Question 309: A 52-year-old man comes to the physician because of malaise and dark urine for the past 5 days. He has also had recurrent episodes of sinus congestion, productive cough, and fever for 3 months. Additionally, he has noticed a rash on his arms and feet. He has seasonal allergic conjunctivitis treated with ketotifen eye drops. Vital signs are within normal limits. Examination shows several erythematous and necrotic papules on his arms and feet. He has inflamed nasopharyngeal mucosa and a perforated nasal septum. The nasal bridge is collapsed. Laboratory studies show:
Hemoglobin 11.3 g/dL
Leukocyte count 12000/mm3
Platelet count 270,000/mm3
ESR 55 mm/hr
Serum
Urea nitrogen 28 mg/dL
Creatinine 2.9 mg/dL
Anti-DNA antibodies negative
Antineutrophil cytoplasmic antibodies positive
Urine
Protein 2+
Glucose negative
RBC 35–37/hpf
RBC casts numerous
Which of the following biopsy findings is most likely to be observed in this patient?
A. Granulomatous vasculitis of small and medium-sized vessels (Correct Answer)
B. Immunoglobulin and complement deposits at the dermoepidermal junction
C. Nongranulomatous fibrinoid necrosis with infiltration of neutrophils
D. Tissue eosinophilia with granulomatous reactions
E. Transmural necrotizing arteritis and fibrinoid necrosis in muscles
Explanation: ***Granulomatous vasculitis of small and medium-sized vessels***
* This client's presentation with **recurrent sinusitis**, **perforated nasal septum** with a collapsed nasal bridge (indicating saddle nose deformity), lung involvement (productive cough), **skin rash** (erythematous and necrotic papules), and **rapidly progressive glomerulonephritis** (dark urine, elevated creatinine, RBC casts, proteinuria) is highly characteristic of **granulomatosis with polyangiitis (GPA)**.
* **Positive ANCA** (specifically PR3-ANCA/c-ANCA) further supports the diagnosis of GPA, which is histopathologically defined by **granulomatous inflammation** and **vasculitis of small to medium-sized vessels**.
*Immunoglobulin and complement deposits at the dermoepidermal junction*
* This finding is characteristic of **Lupus Erythematosus**, particularly in the skin, where it is known as the **lupus band test**.
* The patient's symptoms (e.g., severe renal involvement with RBC casts, saddle nose deformity, positive ANCA) and negative anti-DNA antibodies do not align with a diagnosis of lupus.
*Nongranulomatous fibrinoid necrosis with infiltration of neutrophils*
* This description is more typical of **microscopic polyangiitis (MPA)** or **ANCA-associated vasculitis without granuloma formation**.
* While MPA is ANCA-positive and causes rapidly progressive glomerulonephritis and pulmonary infiltrates, it generally lacks the prominent **granulomatous inflammation** and upper airway destruction (perforated nasal septum, saddle nose deformity) seen in GPA.
*Tissue eosinophilia with granulomatous reactions*
* This finding is characteristic of **eosinophilic granulomatosis with polyangiitis (EGPA)**, formerly Churg-Strauss syndrome.
* EGPA is strongly associated with **asthma** and **peripheral eosinophilia**, neither of which are prominent features in this patient's presentation.
*Transmural necrotizing arteritis and fibrinoid necrosis in muscles*
* These are hallmark features of **polyarteritis nodosa (PAN)**, which involves **medium-sized muscular arteries** but typically **spares the lungs** and **is not associated with ANCA**.
* The patient's significant pulmonary involvement (productive cough) and positive ANCA make PAN an unlikely diagnosis.
Question 310: An 8-year-old boy is brought to the pediatric emergency department by his parents with a complaint of abdominal pain and diarrhea for the past week. He states that for the past two days, he has noticed blood in his stool. His parents note that they attended a neighbor’s barbecue last weekend, but otherwise have not eaten any new foods or changed their usual diet. The patient is admitted to the hospital unit for further work-up. The provider team finds that the patient’s blood is positive for Shiga-like toxin and notes the following lab values: creatinine of 4.2 mg/dL, platelet count of 50,000/mm^3, and hemoglobin of 6.0 g/dL. Which of the following additional lab findings would be consistent with the diagnosis?
A. Microthrombi within glomerular vessels on kidney biopsy (Correct Answer)
B. Blunting of villi on ileal biopsy
C. Crypt abscesses and ulcers on colonic biopsy
D. Foamy macrophages in intestinal lamina propria on duodenal biopsy
E. Sickling of red blood cells on peripheral blood smear
Explanation: ***Microthrombi within glomerular vessels on kidney biopsy***
- The clinical presentation (bloody diarrhea, elevated **creatinine**, low **platelets**, and low **hemoglobin**), a history of recent barbecue exposure, and presence of **Shiga-like toxin** are classic for **hemolytic uremic syndrome (HUS)**, typically caused by *E. coli* O157:H7.
- **HUS** is characterized by a **microangiopathic hemolytic anemia**, **thrombocytopenia**, and **acute kidney injury**, which pathology often reveals **microthrombi** in the glomerular capillaries.
*Blunting of villi on ileal biopsy*
- **Villus blunting** is characteristic of **celiac disease** or other malabsorptive syndromes but is not directly associated with the acute presentation of bloody diarrhea, kidney injury, and thrombocytopenia seen in HUS.
- **Celiac disease** typically presents with chronic diarrhea and malabsorption, not acute onset bloody diarrhea and hemolytic markers.
*Crypt abscesses and ulcers on colonic biopsy*
- These findings are typical of **inflammatory bowel disease (IBD)**, particularly **ulcerative colitis**, or severe infectious colitis like that caused by *Clostridium difficile*.
- While there is bloody diarrhea, the presence of **Shiga-like toxin**, **thrombocytopenia**, and **acute kidney injury** points away from IBD as the primary diagnosis.
*Foamy macrophages in intestinal lamina propria on duodenal biopsy*
- The presence of **foamy macrophages** in the lamina propria is characteristic of **Whipple's disease**, a rare systemic bacterial infection.
- This disease typically presents with chronic malabsorption, arthralgias, and neurological symptoms, which are distinct from the acute presentation of HUS.
*Sickling of red blood cells on peripheral blood smear*
- **Sickling of red blood cells** is diagnostic of **sickle cell anemia** or **sickle cell disease**, a genetic disorder.
- While it can cause hemolytic anemia and kidney complications, the presence of **Shiga-like toxin** and the specific clinical picture strongly point to HUS, not sickle cell crisis.