An 8-year-old girl is brought to the emergency department because of a 2-day history of an intermittent, diffuse abdominal pain. She has also had a nonpruritic rash on her legs and swelling of her ankles for 1 week. Two weeks ago, she had a sore throat, which was treated with oral amoxicillin. Examination of the lower extremities shows non-blanching, raised erythematous papules. The ankle joints are swollen and warm, and their range of motion is limited by pain. Laboratory studies show a platelet count of 450,000/mm3. Test of the stool for occult blood is positive. Which of the following is the most likely diagnosis?
Q262
A 13-year-old boy is brought to the physician because of swelling around his eyes for the past 2 days. His mother also notes that his urine became gradually darker during this time. Three weeks ago, he was treated for bacterial tonsillitis. His temperature is 37.6°C (99.7°F), pulse is 79/min, and blood pressure is 158/87 mm Hg. Examination shows periorbital swelling. Laboratory studies show:
Serum
Urea nitrogen 9 mg/dL
Creatinine 1.7 mg/dL
Urine
Protein 2+
RBC 12/hpf
RBC casts numerous
A renal biopsy would most likely show which of the following findings?
Q263
A 68-year-old man comes to the physician because of a 2-day history of a rash across his trunk and extremities. For the past 3 months, he has had persistent pruritus in these areas. He started hiking in the woods with his grandson last week to try to lose weight. His grandson, who often spends the weekends with him, recently had impetigo. He has hypertension, hyperlipidemia, and osteoarthritis of his thumbs. Five months ago, he was treated for a gout attack of his left hallux. Current medications include captopril, hydrochlorothiazide, simvastatin, allopurinol, and ibuprofen. Vital signs are within normal limits. There are diffuse vesicles and tense blisters involving the chest, flexures of the arms, and shoulders. Rubbing the skin on his chest does not produce blisters. Oral examination shows no abnormalities. This patient's condition is most likely associated with which of the following findings?
Q264
A 6-year-old male presents to the emergency department after falling from his scooter. The patient reports that he fell sideways off the scooter as he rounded a curve in the road, and he describes dull, aching pain along his left side where he hit the ground. The patient’s parents report that he has never had any serious injury but that he has always seemed to bruise easily, especially after he started playing youth soccer this fall. His parents deny that he has ever had nosebleeds or bleeding from the gums, and they have never seen blood in his stool or urine. His mother notes that her brother has had similar problems. On physical exam, the patient has extensive bruising of the lateral left thigh and tenderness to palpation. Laboratory tests are performed and reveal the following:
Hemoglobin: 14 g/dL
Hematocrit: 41%
Mean corpuscular volume: 89 µm3
Reticulocyte count: 0.8%
Leukocyte count: 4,700/mm3
Prothrombin time (PT): 13 seconds
Partial thromboplastin time (PTT): 56 seconds
Bleeding time (BT): 4 minutes
Which of the following is the most likely underlying pathophysiology of this patient's presentation?
Q265
A 58-year-old man comes to the physician because of a 3-month history of diffuse muscle pain, malaise, pain in both knees, recurrent episodes of abdominal and chest pain. He has also had a 5-kg (11-lb) weight loss over the past 4 months. Four years ago, he was diagnosed with chronic hepatitis B infection and was started on tenofovir. There are several ulcerations around the ankle and calves bilaterally. Perinuclear anti-neutrophil cytoplasmic antibodies are negative. Urinalysis shows proteinuria and hematuria. Muscle biopsy shows a transmural inflammation of the arterial wall with leukocytic infiltration and fibrinoid necrosis. Which of the following is the most likely diagnosis?
Q266
An 8-year-old boy is brought by his mother to his pediatrician because his urine is tea-colored and his face has appeared puffy for the past 2 days. He suffered a fever and sore throat several weeks ago that was treated with ibuprofen. The boy was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. Today, his heart rate is 100/min, the respiratory rate is 22/min, the blood pressure is 130/80 mm Hg, and the temperature is 36.8°C (98.2°F). On physical exam the boy has mild periorbital swelling. A urine dipstick reveals 1+ proteinuria and urinalysis reveals 10–15 red cells/high power field and dysmorphic red cells. The pediatrician is concerned with the child’s hypertension, facial edema, and abnormal urine analysis results. Which of the following best represents the mechanism of this patient’s condition?
Q267
A 39-year-old man presents to his primary care physician with new onset lower extremity edema, fatigue, and hematuria. His symptoms began approximately 2 weeks prior to presentation and have progressively worsened. Medical history is significant for opioid-use disorder with heroin treated with methadone. He is in a monogamous relationship with a female partner of 4 years and does not use condoms. He denies cigarette smoking, alcohol use, and last used heroin approximately 1 month ago. His temperature is 99°F (37.2°C), blood pressure is 152/98 mmHg, pulse is 83/min, and respirations are 17/min. On physical exam, there is conjunctival pallor, scleral icterus, a 14 cm liver span, acrocyanosis, and lower extremity 2+ pitting edema. Urinalysis demonstrates proteinuria and dysmorphic red blood cells. Laboratory testing reveals a mildly decreased C3 and decreased C4 serum concentration. Which of the following will most likely be present on renal biopsy in this patient?
Q268
A 73-year-old man dies 4 months after being diagnosed with advanced adenocarcinoma of the colon. Examination of the heart at autopsy shows vegetations lining the mitral valve margins. The vegetations are loosely attached and can be easily scraped off. Microscopic examination shows the vegetations to be composed of interwoven fibrin strands with mononuclear cells. The mitral valve endothelium is intact. Which of the following is the most likely underlying cause of these autopsy findings?
Q269
A 36-year-old woman comes to the physician for evaluation of unintentional weight gain of 5.5 kg (12.2 lb) and irregular menstrual cycles over the past 2 months. She does not take any medications. Her blood pressure is 155/85 mm Hg. Physical examination shows central obesity, hyperpigmentation of the palmar creases, and violaceous scarring of the abdomen. Early morning serum cortisol levels are elevated and serum adrenocorticotropic hormone (ACTH) is within the reference range after a low-dose dexamethasone suppression test. A high-dose dexamethasone suppression test shows suppression of ACTH. Further evaluation is most likely to show which of the following findings?
Q270
A 3-year-old African-American boy presents with a rapid onset of severe abdominal pain. He has a palpably enlarged mass in the left upper quadrant of his abdomen. Complete blood count is notable for a hemoglobin of 7.2 g/dL. Serum haptoglobin level returns normal. Serum unconjugated bilirubin is elevated. The corrected reticulocyte count is elevated. Which of the following is the most likely explanation for the findings above?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 261: An 8-year-old girl is brought to the emergency department because of a 2-day history of an intermittent, diffuse abdominal pain. She has also had a nonpruritic rash on her legs and swelling of her ankles for 1 week. Two weeks ago, she had a sore throat, which was treated with oral amoxicillin. Examination of the lower extremities shows non-blanching, raised erythematous papules. The ankle joints are swollen and warm, and their range of motion is limited by pain. Laboratory studies show a platelet count of 450,000/mm3. Test of the stool for occult blood is positive. Which of the following is the most likely diagnosis?
A. Familial Mediterranean fever
B. Henoch-Schönlein purpura (Correct Answer)
C. Acute rheumatic fever
D. Immune thrombocytopenic purpura
E. Juvenile idiopathic arthritis
Explanation: ***Henoch-Schönlein purpura***
- The constellation of **palpable purpura** on the lower extremities, **arthralgia** (swollen ankles), **abdominal pain**, and **gastrointestinal bleeding** (occult blood in stool) in a child, especially following a recent upper respiratory infection, is highly characteristic of Henoch-Schönlein purpura (now known as **IgA vasculitis**).
- The normal to elevated platelet count (450,000/mm3) rules out conditions causing purpura due to thrombocytopenia and supports a primary vasculitic process.
*Familial Mediterranean fever*
- This is an **autosomal recessive** disorder characterized by recurrent episodes of fever, serositis (peritonitis, pleuritis, pericarditis), and arthritis, but typically **lacks the characteristic vasculitic rash** and gastrointestinal bleeding seen here.
- While fever might be present, the specific rash and GI involvement make it less likely.
*Acute rheumatic fever*
- This condition can present with migratory **polyarthritis**, carditis, chorea, erythema marginatum, and subcutaneous nodules, usually following a **Streptococcal infection**.
- However, it does not typically cause **palpable purpura** or significant **gastrointestinal bleeding**.
*Immune thrombocytopenic purpura*
- Characterized by **isolated thrombocytopenia** leading to petechiae, purpura, and bleeding, typically **without systemic symptoms** like joint swelling or significant abdominal pain unless severe bleeding is present.
- The patient's **elevated platelet count** (450,000/mm3) directly contradicts this diagnosis.
*Juvenile idiopathic arthritis*
- This is a chronic inflammatory arthritis that commonly presents with joint pain and swelling.
- However, it typically **does not cause palpable purpura** or **gastrointestinal bleeding**, which are prominent features in this case.
Question 262: A 13-year-old boy is brought to the physician because of swelling around his eyes for the past 2 days. His mother also notes that his urine became gradually darker during this time. Three weeks ago, he was treated for bacterial tonsillitis. His temperature is 37.6°C (99.7°F), pulse is 79/min, and blood pressure is 158/87 mm Hg. Examination shows periorbital swelling. Laboratory studies show:
Serum
Urea nitrogen 9 mg/dL
Creatinine 1.7 mg/dL
Urine
Protein 2+
RBC 12/hpf
RBC casts numerous
A renal biopsy would most likely show which of the following findings?
A. Effacement of podocyte foot processes on electron microscopy
B. Granular deposits of IgG, IgM, and C3 on immunofluorescence (Correct Answer)
C. Splitting and alternating thickening and thinning of the glomerular basement membrane on light microscopy
D. Mesangial IgA deposits on immunofluorescence
E. "Spike-and-dome" appearance of subepithelial deposits on electron microscopy
Explanation: ***Granular deposits of IgG, IgM, and C3 on immunofluorescence***
- This finding is characteristic of **post-streptococcal glomerulonephritis (PSGN)**, supported by the history of recent tonsillitis, periorbital swelling, dark urine, hypertension, and features of nephritic syndrome (RBC casts, proteinuria).
- The granular deposition pattern reflects the immune complex-mediated nature of PSGN, where **antigen-antibody complexes** deposit in the glomeruli.
*Effacement of podocyte foot processes on electron microscopy*
- This is the hallmark finding in **minimal change disease**, which typically presents with abrupt onset of nephrotic syndrome (severe proteinuria, hypoalbuminemia, edema) without hematuria or hypertension.
- The patient's presentation with **dark urine** (hematuria), hypertension, and RBC casts is inconsistent with minimal change disease.
*Splitting and alternating thickening and thinning of the glomerular basement membrane on light microscopy*
- This describes the characteristic changes seen in **Alport syndrome**, an inherited disorder affecting collagen IV.
- Alport syndrome presents with **hematuria**, progressive renal failure, and often includes hearing loss and ocular abnormalities, which are not mentioned in this acute presentation.
*Mesangial IgA deposits on immunofluorescence*
- This is the diagnostic feature of **IgA nephropathy (Berger's disease)**.
- IgA nephropathy often presents with **recurrent macroscopic hematuria** occurring concurrent with or shortly after an upper respiratory infection, rather than 2-3 weeks later like PSGN.
*"Spike-and-dome" appearance of subepithelial deposits on electron microscopy*
- This appearance is characteristic of **membranous nephropathy**, which is a common cause of **nephrotic syndrome** in adults.
- Membranous nephropathy typically presents with significant proteinuria and edema, and it is less common in children with acute nephritic symptoms like those described.
Question 263: A 68-year-old man comes to the physician because of a 2-day history of a rash across his trunk and extremities. For the past 3 months, he has had persistent pruritus in these areas. He started hiking in the woods with his grandson last week to try to lose weight. His grandson, who often spends the weekends with him, recently had impetigo. He has hypertension, hyperlipidemia, and osteoarthritis of his thumbs. Five months ago, he was treated for a gout attack of his left hallux. Current medications include captopril, hydrochlorothiazide, simvastatin, allopurinol, and ibuprofen. Vital signs are within normal limits. There are diffuse vesicles and tense blisters involving the chest, flexures of the arms, and shoulders. Rubbing the skin on his chest does not produce blisters. Oral examination shows no abnormalities. This patient's condition is most likely associated with which of the following findings?
A. Subepidermal separation with full thickness epidermal necrosis on skin biopsy
B. Spongiotic dermatitis on skin biopsy
C. Antibodies to tissue transglutaminase on serologic testing
D. Growth of Gram-positive bacteria on blood culture
E. Linear deposits of IgG and C3 along the basement membrane on direct immunofluorescence studies (Correct Answer)
Explanation: ***Linear deposits of IgG and C3 along the basement membrane on direct immunofluorescence studies***
- The patient's presentation of **tense blisters** on the trunk and extremities, along with **pruritus**, in an older individual, is highly suggestive of **bullous pemphigoid**.
- **Direct immunofluorescence** showing **linear deposits of IgG and C3** along the **dermal-epidermal junction** (basement membrane zone) is the hallmark diagnostic finding for bullous pemphigoid.
*Subepidermal separation with full thickness epidermal necrosis on skin biopsy*
- This finding, particularly with **epidermal necrosis**, is characteristic of conditions like **toxic epidermal necrolysis (TEN)** or severe **drug reactions**, which typically present with widespread epidermal detachment and often systemic symptoms, unlike this patient's localized tense blisters.
- While subepidermal separation occurs in bullous pemphigoid, **full-thickness epidermal necrosis** is not a typical feature and would indicate a different, more severe pathology.
*Spongiotic dermatitis on skin biopsy*
- **Spongiotic dermatitis** (eczema) is characterized by **intercellular edema** (spongiosis) in the epidermis and typically presents with erythematous, scaly, and pruritic patches or plaques, sometimes with vesicles, but usually not large, tense bullae.
- This finding is more consistent with conditions like **allergic contact dermatitis** or **atopic dermatitis**, which differ significantly from the described blister morphology.
*Antibodies to tissue transglutaminase on serologic testing*
- **Antibodies to tissue transglutaminase (tTG)** are **serological markers for celiac disease**, an autoimmune condition affecting the small intestine.
- While celiac disease can be associated with **dermatitis herpetiformis** (which presents with pruritic papules and vesicles, often on elbows and knees, and granular IgA deposits), it does not cause the large, tense bullae of bullous pemphigoid, and the serologic findings are distinct.
*Growth of Gram-positive bacteria on blood culture*
- A positive blood culture for **Gram-positive bacteria** would indicate **bacteremia** or **sepsis**, which is typically associated with systemic signs of infection (fever, chills, hemodynamic instability) and can sometimes manifest with secondary skin lesions.
- The patient's current presentation is of a primary blistering skin condition with normal vital signs, making a primary bacterial infection the cause of the rash less likely.
Question 264: A 6-year-old male presents to the emergency department after falling from his scooter. The patient reports that he fell sideways off the scooter as he rounded a curve in the road, and he describes dull, aching pain along his left side where he hit the ground. The patient’s parents report that he has never had any serious injury but that he has always seemed to bruise easily, especially after he started playing youth soccer this fall. His parents deny that he has ever had nosebleeds or bleeding from the gums, and they have never seen blood in his stool or urine. His mother notes that her brother has had similar problems. On physical exam, the patient has extensive bruising of the lateral left thigh and tenderness to palpation. Laboratory tests are performed and reveal the following:
Hemoglobin: 14 g/dL
Hematocrit: 41%
Mean corpuscular volume: 89 µm3
Reticulocyte count: 0.8%
Leukocyte count: 4,700/mm3
Prothrombin time (PT): 13 seconds
Partial thromboplastin time (PTT): 56 seconds
Bleeding time (BT): 4 minutes
Which of the following is the most likely underlying pathophysiology of this patient's presentation?
A. Factor VIII deficiency (Correct Answer)
B. Anti-platelet antibodies
C. Factor IX deficiency
D. Factor VIII antigen deficiency
E. GP1b deficiency
Explanation: ***Factor VIII deficiency***
- The patient's presentation with **easy bruising** and a **prolonged PTT** coupled with a normal PT, bleeding time, and platelet count strongly points to a **coagulation factor deficiency** in the intrinsic pathway.
- The **X-linked recessive inheritance** pattern (mother's brother had similar problems) in a male child is classic for **Hemophilia A**, which is caused by a deficiency in Factor VIII.
- Hemophilia A is the **most common hereditary coagulation disorder**, accounting for approximately 80% of hemophilia cases, making it the most likely diagnosis in the absence of specific factor assays.
*Anti-platelet antibodies*
- Anti-platelet antibodies typically cause **immune thrombocytopenia (ITP)**, leading to a **low platelet count** and a **prolonged bleeding time**.
- This patient has a normal platelet count and bleeding time, making ITP unlikely.
*Factor IX deficiency*
- **Factor IX deficiency (Hemophilia B)** also presents with a prolonged PTT and has an X-linked recessive inheritance pattern similar to Hemophilia A.
- Hemophilia A and B are **clinically indistinguishable** without specific factor assays. However, Hemophilia A is approximately **4 times more common** than Hemophilia B, making Factor VIII deficiency the more likely diagnosis based on epidemiology.
*Factor VIII antigen deficiency*
- A deficiency in **Factor VIII antigen** is typically associated with **von Willebrand disease (vWD)**, which often presents with mucocutaneous bleeding (nosebleeds, gum bleeding).
- vWD would also typically feature a **prolonged bleeding time** due to impaired platelet adhesion, which is **not seen in this patient** (BT = 4 minutes, which is normal).
*GP1b deficiency*
- **GP1b deficiency** is characteristic of **Bernard-Soulier syndrome**, a qualitative platelet disorder.
- This would result in **thrombocytopenia** (low platelet count) and a **prolonged bleeding time**, neither of which are present in this patient.
Question 265: A 58-year-old man comes to the physician because of a 3-month history of diffuse muscle pain, malaise, pain in both knees, recurrent episodes of abdominal and chest pain. He has also had a 5-kg (11-lb) weight loss over the past 4 months. Four years ago, he was diagnosed with chronic hepatitis B infection and was started on tenofovir. There are several ulcerations around the ankle and calves bilaterally. Perinuclear anti-neutrophil cytoplasmic antibodies are negative. Urinalysis shows proteinuria and hematuria. Muscle biopsy shows a transmural inflammation of the arterial wall with leukocytic infiltration and fibrinoid necrosis. Which of the following is the most likely diagnosis?
A. Granulomatosis with polyangiitis
B. Thromboangiitis obliterans
C. Polyarteritis nodosa (Correct Answer)
D. Giant cell arteritis
E. Microscopic polyangiitis
Explanation: ***Polyarteritis nodosa***
- The constellation of **diffuse muscle pain**, **constitutional symptoms** (malaise, weight loss), **arthralgia** (knee pain), **abdominal and chest pain**, **cutaneous ulcerations**, and **renal involvement** (proteinuria, hematuria) are classic features of **polyarteritis nodosa (PAN)**. The **transmural inflammation of the arterial wall with leukocytic infiltration and fibrinoid necrosis** on muscle biopsy confirms the diagnosis.
- A significant association exists between **Hepatitis B infection** and **PAN**, making this diagnosis highly likely in a patient with chronic Hepatitis B.
*Granulomatosis with polyangiitis*
- Characterized by **granulomatous inflammation** of the respiratory tract, **glomerulonephritis**, and **small vessel vasculitis**. This patient's biopsy shows transmural inflammation of medium-sized arteries, not granulomas.
- It classically presents with **positive c-ANCA** (cytoplasmic anti-neutrophil cytoplasmic antibodies), whereas this patient's p-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies) are negative, and c-ANCA was not mentioned.
*Thromboangiitis obliterans*
- Primarily affects **small and medium-sized arteries and veins** of the extremities, leading to **ischemia** and sometimes gangrene, especially in **smokers**. While ulcerations are present, the systemic involvement (abdominal pain, chest pain, renal disease) and the biopsy findings are not typical for this condition.
- The pathology of thromboangiitis obliterans involves an **inflammatory thrombus** occluding the vessel, rather than the transmural inflammation and fibrinoid necrosis seen in PAN.
*Giant cell arteritis*
- Typically affects **large and medium-sized arteries**, predominantly in individuals over 50 (which fits the patient's age). However, it classically presents with **headache**, **jaw claudication**, and risk of **vision loss** due to temporal artery involvement.
- Biopsy would show **skip lesions** with **granulomatous inflammation** and **multinucleated giant cells**, which are not described in the patient's muscle biopsy.
*Microscopic polyangiitis*
- A **small vessel vasculitis** characterized by **necrotizing glomerulonephritis** and **pulmonary capillaritis**. It is often associated with **p-ANCA** positivity.
- The biopsy demonstrating **transmural inflammation of a medium-sized artery** is inconsistent with microscopic polyangiitis, which typically affects smaller vessels and rarely shows fibrinoid necrosis.
Question 266: An 8-year-old boy is brought by his mother to his pediatrician because his urine is tea-colored and his face has appeared puffy for the past 2 days. He suffered a fever and sore throat several weeks ago that was treated with ibuprofen. The boy was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. Today, his heart rate is 100/min, the respiratory rate is 22/min, the blood pressure is 130/80 mm Hg, and the temperature is 36.8°C (98.2°F). On physical exam the boy has mild periorbital swelling. A urine dipstick reveals 1+ proteinuria and urinalysis reveals 10–15 red cells/high power field and dysmorphic red cells. The pediatrician is concerned with the child’s hypertension, facial edema, and abnormal urine analysis results. Which of the following best represents the mechanism of this patient’s condition?
A. Complement-independent reaction
B. Diffuse mesangial IgA deposition
C. Immune complex deposition (Correct Answer)
D. Podocyte injury
E. Complement-dependent antibody reaction
Explanation: ***Immune complex deposition***
- The patient's history of a recent **streptococcal infection** (sore throat), followed by **tea-colored urine**, **facial puffiness**, hypertension, and hematuria with dysmorphic red cells, is highly suggestive of **post-streptococcal glomerulonephritis (PSGN)**.
- PSGN is characterized by the deposition of **immune complexes** (containing bacterial antigens, antibodies, and complement) in the glomerular basement membrane and mesangium, leading to inflammation and injury.
*Complement-independent reaction*
- This option is incorrect because PSGN is a **type III hypersensitivity reaction** heavily involving the **complement system**.
- Activation of complement by immune complexes plays a crucial role in mediating glomerular injury in PSGN.
*Diffuse mesangial IgA deposition*
- This is characteristic of **IgA nephropathy** (Berger's disease), which typically presents with **recurrent gross hematuria** often coincident with or immediately following an upper respiratory infection.
- While both can present with hematuria, the lag period and diffuse immune complex deposition pattern in PSGN differentiate it from IgA nephropathy.
*Podocyte injury*
- Podocyte injury is characteristic of **minimal change disease** or **focal segmental glomerulosclerosis**, which typically present with **nephrotic syndrome** (heavy proteinuria, hypoalbuminemia, severe edema).
- This patient presents with features of **nephritic syndrome** (hematuria, mild proteinuria, hypertension, edema).
*Complement-dependent antibody reaction*
- While PSGN involves complement, the primary mechanism is **immune complex deposition**, not direct complement-dependent antibody-mediated cytotoxicity against glomerular components (which would be more akin to anti-GBM disease if antibodies directly target the basement membrane).
- In PSGN, the immune complexes themselves activate complement, leading to inflammation.
Question 267: A 39-year-old man presents to his primary care physician with new onset lower extremity edema, fatigue, and hematuria. His symptoms began approximately 2 weeks prior to presentation and have progressively worsened. Medical history is significant for opioid-use disorder with heroin treated with methadone. He is in a monogamous relationship with a female partner of 4 years and does not use condoms. He denies cigarette smoking, alcohol use, and last used heroin approximately 1 month ago. His temperature is 99°F (37.2°C), blood pressure is 152/98 mmHg, pulse is 83/min, and respirations are 17/min. On physical exam, there is conjunctival pallor, scleral icterus, a 14 cm liver span, acrocyanosis, and lower extremity 2+ pitting edema. Urinalysis demonstrates proteinuria and dysmorphic red blood cells. Laboratory testing reveals a mildly decreased C3 and decreased C4 serum concentration. Which of the following will most likely be present on renal biopsy in this patient?
A. Normal appearing glomerulus
B. Apple-green birefringence on Congo red stain
C. Glomerular basement membrane thinning and splitting
D. Enlarged and hypercellular glomeruli
E. Diffuse mesangial cell proliferation with capillary wall thickening (Correct Answer)
Explanation: ***Diffuse mesangial cell proliferation with capillary wall thickening***
- This patient's **IV drug use history**, **hepatomegaly with scleral icterus**, combined with **nephritic-nephrotic syndrome** (edema, hematuria, proteinuria, hypertension) and **low C3 AND C4** strongly suggests **Hepatitis C-associated Membranoproliferative Glomerulonephritis (MPGN Type I)**.
- The key diagnostic clue is **both C3 and C4 are decreased**, indicating **classical complement pathway activation** (unlike post-infectious GN which shows low C3 with normal C4). This pattern is characteristic of **cryoglobulinemia** associated with Hepatitis C infection.
- **MPGN Type I** shows characteristic **mesangial cell proliferation** and **capillary wall thickening** (double contour/"tram-track" appearance on silver stain) due to **subendothelial immune complex deposition** and mesangial interposition.
- IV drug users have high rates of **Hepatitis C infection**, which can cause type II cryoglobulinemia leading to MPGN with this exact complement pattern and histologic appearance.
*Normal appearing glomerulus*
- Completely inconsistent with this patient's significant **nephritic-nephrotic syndrome** (proteinuria, hematuria with dysmorphic RBCs, edema, hypertension).
- Would not explain the **complement consumption** or progressive renal dysfunction.
*Apple-green birefringence on Congo red stain*
- This finding is pathognomonic for **amyloidosis**, which can cause nephrotic syndrome in IV drug users ("skin-popping" amyloidosis from subcutaneous injection).
- However, amyloidosis typically presents with **nephrotic syndrome alone** (not nephritic features like hematuria with dysmorphic RBCs), does **not cause complement consumption**, and shows apple-green birefringence rather than proliferative changes.
*Glomerular basement membrane thinning and splitting*
- **GBM thinning** is seen in **thin basement membrane disease** (benign familial hematuria), while **GBM splitting** is seen in **Alport syndrome**.
- These are **hereditary conditions** presenting earlier in life, typically without acute nephrotic syndrome, hypertension, or complement abnormalities.
- The acute presentation with complement consumption argues against these diagnoses.
*Enlarged and hypercellular glomeruli*
- While this describes **endocapillary proliferative glomerulonephritis** (like post-streptococcal GN), it lacks the specific feature of **capillary wall thickening** that is crucial for MPGN.
- Post-streptococcal GN would show **low C3 with normal C4** (alternative pathway), not the low C3 and C4 pattern seen here.
- The chronic liver disease signs (hepatomegaly, icterus) point to Hepatitis C-associated disease rather than post-infectious GN.
Question 268: A 73-year-old man dies 4 months after being diagnosed with advanced adenocarcinoma of the colon. Examination of the heart at autopsy shows vegetations lining the mitral valve margins. The vegetations are loosely attached and can be easily scraped off. Microscopic examination shows the vegetations to be composed of interwoven fibrin strands with mononuclear cells. The mitral valve endothelium is intact. Which of the following is the most likely underlying cause of these autopsy findings?
A. Bacterial colonization
B. Metastatic infiltration
C. Procoagulant release (Correct Answer)
D. Antibody cross-reactivity
E. Dystrophic calcifications
Explanation: ***Procoagulant release***
- The patient has **adenocarcinoma of the colon**, a malignancy known to be associated with **nonbacterial thrombotic endocarditis (NBTE)**, also known as marantic endocarditis.
- Tumors, particularly adenocarcinomas, can release **procoagulant factors** (e.g., mucin, thromboplastin) that activate the coagulation cascade, leading to the formation of **fibrin and platelet vegetations** on otherwise normal heart valves.
*Bacterial colonization*
- **Bacterial endocarditis** typically involves microbial colonization of the vegetations and often causes more destructive lesions, microabscesses, or ulceration of the valve leaflets.
- The description of **interwoven fibrin strands with mononuclear cells** and an **intact endothelium** without bacterial organisms suggests a sterile process rather than infection.
*Metastatic infiltration*
- While the patient has cancer, **metastatic infiltration** of the heart valves by tumor cells is rare and usually presents as discreet tumor deposits, not as large, easily scraped-off vegetations composed primarily of fibrin and inflammatory cells.
- There is no mention of tumor cells within the vegetations.
*Antibody cross-reactivity*
- **Rheumatic heart disease** involves sterile vegetations (verrucae) due to **antibody cross-reactivity** following Group A streptococcal infection, but these are typically small, firm, and occur on inflamed valve leaflets often years after the inciting event.
- The patient's presentation with a recent cancer diagnosis and the nature of the vegetations do not fit the typical picture of rheumatic heart disease.
*Dystrophic calcifications*
- **Dystrophic calcification** is a hallmark of **aging or damaged heart valves** (e.g., calcific aortic stenosis) and involves the deposition of calcium in necrotic or degenerated tissue.
- The described vegetations are composed of **fibrin and mononuclear cells**, not calcified material, and are easily scraped off, which is not characteristic of dystrophic calcification.
Question 269: A 36-year-old woman comes to the physician for evaluation of unintentional weight gain of 5.5 kg (12.2 lb) and irregular menstrual cycles over the past 2 months. She does not take any medications. Her blood pressure is 155/85 mm Hg. Physical examination shows central obesity, hyperpigmentation of the palmar creases, and violaceous scarring of the abdomen. Early morning serum cortisol levels are elevated and serum adrenocorticotropic hormone (ACTH) is within the reference range after a low-dose dexamethasone suppression test. A high-dose dexamethasone suppression test shows suppression of ACTH. Further evaluation is most likely to show which of the following findings?
A. Atrophy of the pituitary gland
B. Nodular hypertrophy of the zona reticularis
C. Unilateral carcinoma of the adrenal cortex
D. Benign adenoma of the adrenal medulla
E. Bilateral hyperplasia of the zona fasciculata (Correct Answer)
Explanation: ***Bilateral hyperplasia of the zona fasciculata***
- The clinical presentation (weight gain, irregular menses, hypertension, central obesity, hyperpigmentation, violaceous striae) is classic for **Cushing's syndrome**.
- **Elevated early morning cortisol** with **ACTH within reference range** after low-dose dexamethasone (failure to suppress) confirms Cushing's syndrome.
- **Suppression of ACTH with high-dose dexamethasone** indicates **pituitary Cushing's disease** (ACTH-dependent), where a pituitary adenoma secretes excess ACTH.
- Chronic ACTH stimulation leads to **bilateral adrenal hyperplasia**, specifically of the zona fasciculata (which produces cortisol).
*Atrophy of the pituitary gland*
- Pituitary atrophy would cause **decreased ACTH production**, resulting in secondary adrenal insufficiency with low cortisol and low ACTH.
- This contradicts the patient's presentation of hypercortisolism.
*Nodular hypertrophy of the zona reticularis*
- The **zona reticularis** primarily produces androgens (DHEA, androstenedione), not cortisol.
- While it may be affected in Cushing's, the hypercortisolism and clinical features point to excess glucocorticoid production from the **zona fasciculata**, not isolated zona reticularis pathology.
*Unilateral carcinoma of the adrenal cortex*
- Adrenal carcinoma causes **ACTH-independent Cushing's syndrome** with **suppressed ACTH levels** (due to negative feedback from autonomous cortisol production).
- Primary adrenal tumors (adenomas or carcinomas) do **not suppress with high-dose dexamethasone**, which rules out this diagnosis.
*Benign adenoma of the adrenal medulla*
- An adrenal medullary adenoma is a **pheochromocytoma**, which secretes catecholamines (epinephrine, norepinephrine).
- This presents with **paroxysmal hypertension**, headaches, palpitations, and diaphoresis—distinct from the hypercortisolism features described here.
Question 270: A 3-year-old African-American boy presents with a rapid onset of severe abdominal pain. He has a palpably enlarged mass in the left upper quadrant of his abdomen. Complete blood count is notable for a hemoglobin of 7.2 g/dL. Serum haptoglobin level returns normal. Serum unconjugated bilirubin is elevated. The corrected reticulocyte count is elevated. Which of the following is the most likely explanation for the findings above?
A. Intravascular hemolysis
B. Renal infarction
C. Aplastic crisis
D. Extravascular hemolysis (Correct Answer)
E. Acute chest syndrome
Explanation: ***Extravascular hemolysis***
- The combination of **elevated unconjugated bilirubin** and a normal **haptoglobin** level points towards extravascular hemolysis. The spleen, which would be involved in extravascular hemolysis, is enlarged (palpable mass in the LUQ representing splenomegaly).
- The patient's presentation with severe abdominal pain, anemia (Hb 7.2 g/dL), elevated reticulocyte count, and especially in an **African-American child**, suggests a **hemolytic crisis** in the context of **sickle cell disease**, where extravascular hemolysis is common, and an acutely enlarging spleen can signal **splenic sequestration crisis**.
*Intravascular hemolysis*
- In **intravascular hemolysis**, **haptoglobin** would be significantly decreased or undetectable, as it binds to free hemoglobin released into circulation.
- While it presents with anemia and elevated unconjugated bilirubin, the normal haptoglobin level makes it less likely than extravascular hemolysis.
*Renal infarction*
- This typically presents with **flank pain** and may show hematuria or proteinuria, but it does not explain the **anemia**, **elevated reticulocyte count**, or **jaundice** (elevated unconjugated bilirubin).
- A palpable mass in the left upper quadrant is more consistent with **splenomegaly** than a renal infarction.
*Aplastic crisis*
- An **aplastic crisis** would be characterized by a **low reticulocyte count**, indicating bone marrow failure and reduced red blood cell production.
- The patient's **elevated reticulocyte count** directly contradicts an aplastic crisis.
*Acute chest syndrome*
- This condition is characterized by **fever**, **chest pain**, and **pulmonary infiltrates** on chest X-ray.
- While common in **sickle cell disease**, it does not explain the prominent **abdominal mass** or the specific laboratory findings of **hemolysis** (elevated unconjugated bilirubin, normal haptoglobin, elevated reticulocytes).
