A 7-year-old girl is brought to her pediatrician by her mother because of puffiness under both eyes in the morning. The mother reports that the child has just recovered from a seasonal influenza infection a few days ago. Vital signs include: temperature 37°C (98.6°F), blood pressure 100/67 mm Hg, and pulse 95/min. On examination, there is facial edema and bilateral 2+ pitting edema over the legs. Laboratory results are shown:
Serum albumin 2.1 g/dL
Serum triglycerides 200 mg/dL
Serum cholesterol 250 mg/dL
Urine dipstick 4+ protein
Which of the following casts are more likely to be present in this patient’s urine?
Q2
A 6-year-old girl comes with her parents to the physician's office to initiate care with a new physician. The patient was recently adopted and her parents do not know her birth history; however, she has had some issues with fatigue. They were told by the adoption agency that the patient has required blood transfusions for "low blood count" in the past but they are not aware of the reason for these transfusions. Her temperature is 37.8°C (99.8°F), blood pressure is 110/84 mmHg, and pulse is 95/min. Physical examination is notable for conjunctival pallor, pale skin, and mild splenomegaly. A complete blood count is taken in the office with the following results:
Hemoglobin: 6.8 g/dL
Leukocyte count: 5,000/mm^3
Platelet count: 190,000/mm^3
Peripheral smear shows spherocytes and further analysis reveals rigid red blood cells. The most likely cause of this patient's symptoms has which of the following modes of inheritance?
Q3
An investigator is studying the immunologic response to a Staphylococcus aureus toxin in a mouse model. Fourteen days after injecting mice with this toxin, he isolates antibodies against neutrophil proteinase 3 in their sera. A patient with high concentrations of these antibodies would most likely present with which of the following clinical features?
Q4
An 8-year-old boy has a known genetic condition in which the substitution of thymine for adenine in the 6th codon of the beta globin gene leads to a single-point substitution mutation that results in the production of the amino acid valine in place of glutamic acid. The patient comes to the clinic regularly for blood transfusions. What is the most likely laboratory finding that can be observed in this patient?
Q5
A 31-year-old man comes to the emergency department for acute tearing chest pain that radiates to the back. Despite appropriate therapy, the patient dies. Autopsy shows an increase in mucoid extracellular matrix and loss of smooth muscle cell nuclei in the media of large arteries. Which of the following additional findings is most likely in this patient?
Q6
Two hours after undergoing allogeneic kidney transplantation for polycystic kidney disease, a 14-year-old girl has lower abdominal pain. Examination shows tenderness to palpation in the area the donor kidney was placed. Ultrasound of the donor kidney shows diffuse tissue edema. Serum creatinine begins to increase and dialysis is initiated. Which of the following is the most likely cause of this patient's symptoms?
Q7
A 41-year-old African American woman presents to her primary care physician with a 3-week history of lower extremity edema and shortness of breath. She says that she has also noticed that she gets fatigued more easily and has been gaining weight. Her past medical history is significant for sickle cell disease and HIV infection for which she is currently taking combination therapy. Physical exam is significant for periorbital and lower extremity edema. Laboratory testing is significant for hypoalbuminemia, and urinalysis demonstrates 4+ protein. Which of the following would most likely be seen on kidney biopsy in this patient?
Q8
A 34-year-old woman with beta-thalassemia major is brought to the physician because of a 2-month history of fatigue, darkening of her skin, and pain in her ankle joints. She has also had increased thirst and frequent urination for 2 weeks. She receives approximately 5 blood transfusions every year; her last transfusion was 3 months ago. Physical examination shows hyperpigmented skin, scleral icterus, pale mucous membranes, and a liver span of 17 cm. Which of the following serum findings is most likely in this patient?
Q9
A 3-year-old boy is brought to the physician for evaluation of pallor and increasing lethargy for 3 days. Six days ago, he experienced abdominal pain, vomiting, and bloody diarrhea that have since resolved. The family returned from a road trip to Mexico 4-weeks ago. His temperature is 38.8°C (101.8°F), pulse is 128/min, respirations are 30/min, and blood pressure is 96/60 mm Hg. Examination shows pale conjunctivae and scleral icterus. The abdomen is soft, nontender, and nondistended. Bowel sounds are hyperactive. Laboratory studies show:
Hemoglobin 7.8 g/dL
Mean corpuscular volume 92 μm3
Leukocyte count 18,500/mm3
Platelet count 45,000/mm3
Prothrombin time 12 sec
Partial thromboplastin time 34 sec
Serum
Urea nitrogen 32 mg/dL
Creatinine 1.8 mg/dL
Bilirubin
Total 2.0 mg/dL
Direct 0.1 mg/dL
Lactate dehydrogenase 1685 U/L
A peripheral blood smear shows schistocytes. Which of the following is the most likely mechanism of this patient's presentation?
Q10
A 34-year-old woman comes to the physician because of recent fatigue and weakness that is exacerbated by cross-country skiing. Four weeks ago, she was diagnosed with pneumonia; sputum cultures on Eaton agar showed organisms that lacked a cell wall. Physical examination shows conjunctival pallor and cyanosis of the fingertips. Both lungs are clear to auscultation. Which of the following findings is most likely to confirm the diagnosis?
Systemic Pathology US Medical PG Practice Questions and MCQs
Question 1: A 7-year-old girl is brought to her pediatrician by her mother because of puffiness under both eyes in the morning. The mother reports that the child has just recovered from a seasonal influenza infection a few days ago. Vital signs include: temperature 37°C (98.6°F), blood pressure 100/67 mm Hg, and pulse 95/min. On examination, there is facial edema and bilateral 2+ pitting edema over the legs. Laboratory results are shown:
Serum albumin 2.1 g/dL
Serum triglycerides 200 mg/dL
Serum cholesterol 250 mg/dL
Urine dipstick 4+ protein
Which of the following casts are more likely to be present in this patient’s urine?
A. Waxy casts
B. Fatty casts (Correct Answer)
C. Red cell casts
D. Granular casts
E. White cell casts
Explanation: ***Fatty casts***
- The patient's presentation with **facial edema**, **pitting edema**, **hypoalbuminemia**, **hyperlipidemia** (increased triglycerides and cholesterol), and **heavy proteinuria** (4+ protein on urine dipstick) is highly suggestive of **nephrotic syndrome**.
- **Fatty casts** are pathognomonic for **nephrotic syndrome** because they are formed from renal tubular epithelial cells that have absorbed filtered lipids (cholesterol, triglycerides) and subsequently desquamated.
*Waxy casts*
- **Waxy casts** are typically associated with **chronic kidney disease** and indicate severe, longstanding tubular atrophy and dilation, often seen in end-stage renal disease.
- While they can be present in nephrotic syndrome if the kidney damage is severe and chronic, they are not the most characteristic cast *specifically* for the acute onset and hyperlipidemia seen here.
*Red cell casts*
- **Red cell casts** are indicative of **glomerulonephritis** (nephritic syndrome), where red blood cells leak through damaged glomerular capillaries into the renal tubules.
- This patient's presentation is characterized by **heavy proteinuria** and **edema** (nephrotic syndrome), without signs such as hematuria or hypertension that would typically suggest a nephritic picture.
*Granular casts*
- **Granular casts** are formed from degenerated cellular casts (e.g., granular breakdown products of renal tubular epithelial cells) or aggregated plasma proteins, and are non-specific indicators of **kidney damage** or **acute tubular necrosis**.
- While they can be seen in various kidney diseases, including nephrotic syndrome, they are not as specific as fatty casts for the constellation of symptoms presented.
*White cell casts*
- **White cell casts** are typically associated with **pyelonephritis** (kidney infection) or **interstitial nephritis**, indicating inflammation within the renal tubules or interstitium.
- There is no clinical or laboratory evidence of infection or inflammation suggesting pyelonephritis in this patient.
Question 2: A 6-year-old girl comes with her parents to the physician's office to initiate care with a new physician. The patient was recently adopted and her parents do not know her birth history; however, she has had some issues with fatigue. They were told by the adoption agency that the patient has required blood transfusions for "low blood count" in the past but they are not aware of the reason for these transfusions. Her temperature is 37.8°C (99.8°F), blood pressure is 110/84 mmHg, and pulse is 95/min. Physical examination is notable for conjunctival pallor, pale skin, and mild splenomegaly. A complete blood count is taken in the office with the following results:
Hemoglobin: 6.8 g/dL
Leukocyte count: 5,000/mm^3
Platelet count: 190,000/mm^3
Peripheral smear shows spherocytes and further analysis reveals rigid red blood cells. The most likely cause of this patient's symptoms has which of the following modes of inheritance?
A. Autosomal recessive
B. Autosomal dominant (Correct Answer)
C. Mitochondrial inheritance
D. X-linked dominant
E. X-linked recessive
Explanation: ***Autosomal dominant***
- The clinical picture of severe **anemia** requiring transfusions, **splenomegaly**, and peripheral smear findings of **spherocytes** and rigid red blood cells is highly suggestive of **hereditary spherocytosis**.
- **Hereditary spherocytosis** is caused by defects in red blood cell membrane proteins (e.g., spectrin, ankyrin), and the **most common mode of inheritance** for this condition is **autosomal dominant** (approximately 75% of cases).
*Autosomal recessive*
- While approximately **25%** of hereditary spherocytosis cases result from **autosomal recessive inheritance** or de novo mutations, the majority (~75%) follow an autosomal dominant pattern.
- The severity of presentation alone does not distinguish between inheritance patterns; both can present with severe anemia requiring transfusions.
- Other common red blood cell disorders, such as **sickle cell anemia** and **beta-thalassemia**, are autosomal recessive, but their characteristic findings (e.g., sickle cells, target cells) are not described here.
*Mitochondrial inheritance*
- **Mitochondrial disorders** primarily affect organs with high energy demands (e.g., muscles, brain) and do not typically cause isolated hemolytic anemia with spherocytes.
- This mode of inheritance involves genes located in the **mitochondrial DNA** and is passed down exclusively from the mother.
*X-linked dominant*
- **X-linked dominant** disorders affect both males and females (though often more severely in males) and do not fit the typical presentation or known genetic basis of hereditary spherocytosis.
- Examples include **Rett syndrome** and **incontinentia pigmenti**.
*X-linked recessive*
- **X-linked recessive** disorders, such as **G6PD deficiency** or **hemophilia**, are more common in males and have distinct clinical and laboratory features that do not match the patient's presentation of hereditary spherocytosis.
- While **G6PD deficiency** can cause hemolytic anemia, it is typically triggered by oxidative stress and does not primarily involve spherocytes or chronic splenomegaly in the same manner.
Question 3: An investigator is studying the immunologic response to a Staphylococcus aureus toxin in a mouse model. Fourteen days after injecting mice with this toxin, he isolates antibodies against neutrophil proteinase 3 in their sera. A patient with high concentrations of these antibodies would most likely present with which of the following clinical features?
A. Migratory thrombophlebitis and digital ulcers
B. Genital ulcers and anterior uveitis
C. Polyneuropathy and melena
D. Visual impairment and jaw claudication
E. Nasal mucosal ulcerations and hematuria (Correct Answer)
Explanation: ***Nasal mucosal ulcerations and hematuria***
- Antibodies against **neutrophil proteinase 3 (PR3-ANCA)** are characteristic of **granulomatosis with polyangiitis (GPA)**, previously known as Wegener's granulomatosis.
- GPA classically involves the **upper and lower respiratory tracts** (e.g., nasal ulcerations, sinusitis, pulmonary nodules) and the **kidneys** (e.g., glomerulonephritis leading to hematuria), and can also involve the eyes, skin, and joints.
*Migratory thrombophlebitis and digital ulcers*
- **Migratory thrombophlebitis (Trousseau's sign)** is associated with **adenocarcinomas**, particularly pancreatic cancer, and not directly with PR3-ANCA.
- **Digital ulcers** can be seen in various conditions like systemic sclerosis or vasculitis, but are not specific for GPA's primary presentation.
*Genital ulcers and anterior uveitis*
- **Genital ulcers** and **anterior uveitis** are hallmarks of **Behçet's disease**, a systemic vasculitis not typically associated with PR3-ANCA.
- Behçet's disease is characterized by recurrent oral and genital ulcers, ocular inflammation, and skin lesions.
*Polyneuropathy and melena*
- **Polyneuropathy** can be seen in various conditions, including some vasculitides (e.g., polyarteritis nodosa), but is not a primary or most characteristic feature of GPA.
- **Melena (black, tarry stools)** indicates upper gastrointestinal bleeding, which is not a typical presentation of GPA.
*Visual impairment and jaw claudication*
- **Visual impairment** and **jaw claudication** (pain in the jaw after chewing) are classic symptoms of **giant cell arteritis (temporal arteritis)**.
- Giant cell arteritis is a large-vessel vasculitis, distinctly different from the small-vessel vasculitis associated with PR3-ANCA.
Question 4: An 8-year-old boy has a known genetic condition in which the substitution of thymine for adenine in the 6th codon of the beta globin gene leads to a single-point substitution mutation that results in the production of the amino acid valine in place of glutamic acid. The patient comes to the clinic regularly for blood transfusions. What is the most likely laboratory finding that can be observed in this patient?
A. Bone marrow hyperplasia
B. Elevated lactate dehydrogenase (Correct Answer)
C. Hemosiderin
D. Hemoglobinuria
E. Increased serum haptoglobin
Explanation: ***Elevated lactate dehydrogenase***
- The description of a single-point mutation leading to valine in place of glutamic acid in the beta-globin chain is characteristic of **sickle cell anemia**. In sickle cell anemia, chronic hemolytic anemia causes continuous red blood cell destruction.
- **Lactate dehydrogenase (LDH)** is an intracellular enzyme released when red blood cells are destroyed. In chronic hemolysis, **elevated LDH** is a consistent laboratory finding reflecting ongoing cell lysis.
- This is a routine blood test (true laboratory finding) and is characteristically elevated in all hemolytic anemias, including sickle cell disease.
*Bone marrow hyperplasia*
- The bone marrow does undergo **hyperplasia** in response to chronic hemolysis as it increases red blood cell production to compensate for accelerated destruction.
- However, bone marrow hyperplasia is a **histopathological finding** requiring bone marrow biopsy or aspiration, not a routine laboratory test. The question specifically asks for a "laboratory finding."
*Hemosiderin*
- **Hemosiderin** is an iron-storage complex that accumulates in tissues due to iron overload, particularly common in patients receiving frequent blood transfusions.
- While this patient will likely have hemosiderin accumulation (especially given the transfusion history), detecting it requires tissue examination or bone marrow evaluation with iron staining, not a routine laboratory test.
- It reflects iron overload from transfusions rather than the primary hemolytic process.
*Hemoglobinuria*
- **Hemoglobinuria** (hemoglobin in the urine) occurs when free hemoglobin from intravascular hemolysis exceeds the binding capacity of haptoglobin.
- While this can occur during acute hemolytic crises in sickle cell disease, it is **intermittent** rather than a consistent finding.
- Elevated LDH is a more reliable and consistently present laboratory marker of chronic hemolysis.
*Increased serum haptoglobin*
- **Haptoglobin** binds to free hemoglobin released during hemolysis, and its levels are typically **decreased**, not increased, in hemolytic conditions like sickle cell anemia.
- In chronic hemolysis, haptoglobin is consumed by binding free hemoglobin, leading to low or undetectable serum levels.
- Increased haptoglobin would suggest an acute phase response to inflammation or infection, not hemolysis.
Question 5: A 31-year-old man comes to the emergency department for acute tearing chest pain that radiates to the back. Despite appropriate therapy, the patient dies. Autopsy shows an increase in mucoid extracellular matrix and loss of smooth muscle cell nuclei in the media of large arteries. Which of the following additional findings is most likely in this patient?
A. Nasal septum perforation
B. Ectopia lentis (lens dislocation) (Correct Answer)
C. Condylomata lata
D. Pes cavus with hammer toes
E. Pectus carinatum
Explanation: ***Ectopia lentis (lens dislocation)***
- The patient's presentation of acute **tearing chest pain radiating to the back**, with autopsy findings of **mucoid extracellular matrix increase** and **loss of smooth muscle cell nuclei in the media of large arteries** (cystic medial necrosis), is highly suggestive of **Marfan syndrome**.
- **Ectopia lentis** (lens dislocation), particularly upward and temporal, is a classic ocular manifestation of Marfan syndrome, caused by a defect in **fibrillin-1**, a component of suspensory ligaments.
*Nasal septum perforation*
- This is typically associated with conditions like **Wegener's granulomatosis (granulomatosis with polyangiitis)**, repeated cocaine use, or chronic infections, which are not suggested by the clinical picture or autopsy findings.
- It does not specifically relate to the arterial pathology described or a genetic connective tissue disorder.
*Condylomata lata*
- **Condylomata lata** are characteristic painless, flat-topped, moist lesions found in the anogenital region, indicating a manifestation of **secondary syphilis**.
- There is no clinical or pathological evidence to suggest syphilis in this patient.
*Pes cavus with hammer toes*
- **Pes cavus** (high arch) and **hammer toes** can be associated with various neuromuscular disorders (e.g., Charcot-Marie-Tooth disease) or may be idiopathic.
- While Marfan syndrome can have some skeletal abnormalities, these specific foot deformities are not a hallmark feature of the condition, and are less direct than ectopia lentis.
*Pectus carinatum*
- **Pectus carinatum** (pigeon chest) is a protrusion of the sternum, which can indeed be a skeletal manifestation of **Marfan syndrome**.
- However, **ectopia lentis** is an even more distinctive and highly specific feature of Marfan syndrome, and the question asks for the "most likely additional finding" given the strong cardiovascular and histological evidence pointing to Marfan syndrome.
Question 6: Two hours after undergoing allogeneic kidney transplantation for polycystic kidney disease, a 14-year-old girl has lower abdominal pain. Examination shows tenderness to palpation in the area the donor kidney was placed. Ultrasound of the donor kidney shows diffuse tissue edema. Serum creatinine begins to increase and dialysis is initiated. Which of the following is the most likely cause of this patient's symptoms?
A. Preformed antibodies against class I HLA molecules (Correct Answer)
B. Immune complex deposition in donor tissue
C. T-lymphocyte activation by donor HLA peptides
D. Irreversible intimal fibrosis and obstruction of vessels
E. Proliferation of donor T lymphocytes
Explanation: ***Preformed antibodies against class I HLA molecules***
- This scenario describes **hyperacute rejection**, a rapid and severe immune response occurring minutes to hours post-transplant.
- It is mediated by **preformed antibodies** (often anti-HLA antibodies) in the recipient's circulation that bind to donor antigens, leading to complement activation, endothelial damage, and graft thrombosis.
*Immune complex deposition in donor tissue*
- This mechanism is characteristic of **Type III hypersensitivity** reactions, which are not typically involved in hyperacute rejection.
- Immune complex deposition is more common in conditions like **lupus nephritis** or **post-streptococcal glomerulonephritis**, not immediate graft failure.
*T-lymphocyte activation by donor HLA peptides*
- This describes the mechanism of **acute cellular rejection**, which is mediated by host T-lymphocytes recognizing donor HLA antigens.
- Acute rejection typically occurs days to weeks or months after transplantation, not within hours.
*Irreversible intimal fibrosis and obstruction of vessels*
- This process is characteristic of **chronic rejection**, which develops months to years after transplantation.
- Chronic rejection is a slow, progressive decline in graft function due to vascular damage, fibrosis, and ultimately graft failure.
*Proliferation of donor T lymphocytes*
- Proliferation of donor T lymphocytes is not a mechanism of transplant rejection but rather relevant to **graft-versus-host disease (GVHD)**.
- GVHD occurs when immunocompetent T-cells in the donor tissue (e.g., bone marrow transplant) attack recipient tissues.
Question 7: A 41-year-old African American woman presents to her primary care physician with a 3-week history of lower extremity edema and shortness of breath. She says that she has also noticed that she gets fatigued more easily and has been gaining weight. Her past medical history is significant for sickle cell disease and HIV infection for which she is currently taking combination therapy. Physical exam is significant for periorbital and lower extremity edema. Laboratory testing is significant for hypoalbuminemia, and urinalysis demonstrates 4+ protein. Which of the following would most likely be seen on kidney biopsy in this patient?
A. Birefringence under polarized light
B. Segmental scarring (Correct Answer)
C. Subepithelial deposits
D. Expansion of the mesangium
E. Normal glomeruli
Explanation: ***Segmental scarring***
- The patient's history of **HIV infection**, symptoms of **nephrotic syndrome** (edema, weight gain, fatigue, hypoalbuminemia, 4+ proteinuria), and African American ethnicity are highly suggestive of **HIV-associated nephropathy (HIVAN)**.
- HIVAN is a form of **collapsing focal segmental glomerulosclerosis (FSGS)**, a condition characterized by **segmental scarring** and collapse of the glomerular tuft. In HIVAN, this scarring is severe and progressive.
*Birefringence under polarized light*
- This finding is characteristic of **amyloidosis**, where protein deposits (amyloid) accumulate in tissues and exhibit apple-green birefringence under Congo red stain and polarized light.
- While amyloidosis can cause nephrotic syndrome, it is not the most common kidney pathology in an HIV-positive patient with these specific features.
*Subepithelial deposits*
- **Subepithelial deposits** with a characteristic "spike and dome" appearance on electron microscopy are pathognomonic for **membranous glomerulonephritis**.
- This type of glomerulonephritis is not typically associated with HIV infection, nor does it typically present with the rapidly progressive decline seen in HIVAN.
*Expansion of the mesangium*
- **Mesangial expansion** is a common feature in several glomerular diseases, including **diabetic nephropathy** and early-stage IgA nephropathy.
- While it can be present in some forms of FSGS, it is not the primary or most characteristic finding for HIVAN, which is better described by collapsing glomeruli and segmental scarring.
*Normal glomeruli*
- Given the patient's profound **proteinuria (4+)**, hypoalbuminemia, and symptoms of **nephrotic syndrome**, it is highly unlikely that the glomeruli would appear normal on biopsy.
- Normal glomeruli would not explain the significant kidney dysfunction and proteinuria observed in this patient.
Question 8: A 34-year-old woman with beta-thalassemia major is brought to the physician because of a 2-month history of fatigue, darkening of her skin, and pain in her ankle joints. She has also had increased thirst and frequent urination for 2 weeks. She receives approximately 5 blood transfusions every year; her last transfusion was 3 months ago. Physical examination shows hyperpigmented skin, scleral icterus, pale mucous membranes, and a liver span of 17 cm. Which of the following serum findings is most likely in this patient?
A. Decreased transferrin saturation
B. Elevated transferrin
C. Elevated hepcidin
D. Elevated ferritin (Correct Answer)
E. Decreased haptoglobin
Explanation: ***Elevated ferritin***
- The patient has **beta-thalassemia major**, which requires frequent **blood transfusions**, leading to chronic **iron overload**.
- **Ferritin** is a storage protein for iron, and its levels are typically elevated in cases of **hemochromatosis** due to iron overload.
*Decreased transferrin saturation*
- **Transferrin saturation** is a measure of iron bound to transferrin. In iron overload conditions like **hemochromatosis**, **transferrin saturation is typically elevated**, not decreased.
- A decreased percentage would indicate **iron deficiency**, which is not the case here given the history of transfusions and symptoms of iron overload.
*Elevated transferrin*
- **Transferrin** levels are usually **decreased** or normal in iron overload states as the body tries to reduce further iron absorption and transport.
- Elevated transferrin is more characteristic of **iron deficiency anemia**, where the body increases iron transport capacity to obtain more iron.
*Elevated hepcidin*
- **Hepcidin** is a key regulator of iron metabolism, and it is usually **elevated** in response to inflammation and high iron stores to **reduce iron absorption** and release from stores.
- However, in disorders such as **beta-thalassemia**, chronic anemia leads to **erythroid hyperplasia** and the production of factors that **suppress hepcidin production**, contributing to increased iron absorption and overload despite high body iron stores.
*Decreased haptoglobin*
- **Haptoglobin** binds **free hemoglobin** in the blood. It is **decreased** in conditions involving **hemolysis**, which is characteristic of thalassemia major.
- While beta-thalassemia major indeed involves hemolysis causing anemia, the primary clinical picture of darkening skin, joint pain, thirst, frequent urination, and liver enlargement points strongly to **iron overload** and its systemic effects, making elevated ferritin a more direct and comprehensive indicator of the patient's immediate medical crisis.
Question 9: A 3-year-old boy is brought to the physician for evaluation of pallor and increasing lethargy for 3 days. Six days ago, he experienced abdominal pain, vomiting, and bloody diarrhea that have since resolved. The family returned from a road trip to Mexico 4-weeks ago. His temperature is 38.8°C (101.8°F), pulse is 128/min, respirations are 30/min, and blood pressure is 96/60 mm Hg. Examination shows pale conjunctivae and scleral icterus. The abdomen is soft, nontender, and nondistended. Bowel sounds are hyperactive. Laboratory studies show:
Hemoglobin 7.8 g/dL
Mean corpuscular volume 92 μm3
Leukocyte count 18,500/mm3
Platelet count 45,000/mm3
Prothrombin time 12 sec
Partial thromboplastin time 34 sec
Serum
Urea nitrogen 32 mg/dL
Creatinine 1.8 mg/dL
Bilirubin
Total 2.0 mg/dL
Direct 0.1 mg/dL
Lactate dehydrogenase 1685 U/L
A peripheral blood smear shows schistocytes. Which of the following is the most likely mechanism of this patient's presentation?
A. IgA Immune complex-mediated vasculitis
B. Microthrombi formation (Correct Answer)
C. Deficiency of ADAMTS13
D. Bacteremia
E. Infection with an RNA picornavirus
Explanation: ***Microthrombi formation***
- This patient's presentation with **hemolytic anemia** (pallor, lethargy, low hemoglobin, elevated LDH, schistocytes), **thrombocytopenia** (low platelet count), and **acute kidney injury** (elevated BUN and creatinine) following a diarrheal illness, particularly after travel to Mexico (suggesting **Shiga toxin-producing E. coli**), is characteristic of **hemolytic uremic syndrome (HUS)**.
- HUS is mediated by **Shiga toxin**, which damages endothelial cells, leading to the formation of **microthrombi** in small blood vessels, occluding them and causing fragmentation of red blood cells (schistocytes) and platelet consumption.
*IgA Immune complex-mediated vasculitis*
- This describes **Henoch-Schönlein purpura (HSP)**, which typically presents with palpable purpura, abdominal pain, arthralgia, and renal involvement (hematuria/proteinuria), but usually without the severe microangiopathic hemolytic anemia and thrombocytopenia seen here.
- While HSP can follow an infection, the primary mechanism involves **IgA deposition** in small vessels, not Shiga toxin-induced microthrombi.
*Deficiency of ADAMTS13*
- A severe deficiency (<10%) of **ADAMTS13** (a von Willebrand factor-cleaving protease) is the hallmark of **thrombotic thrombocytopenic purpura (TTP)**.
- While TTP shares features like microangiopathic hemolytic anemia and thrombocytopenia, it is typically distinguished from HUS by prominent **neurological symptoms** and fever, and less severe renal involvement. The recent diarrheal illness strongly points away from typical TTP.
*Bacteremia*
- While bacteremia can cause sepsis and lead to disseminated intravascular coagulation (DIC), this patient's clinical picture is more specific for HUS, characterized by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury following a diarrheal prodrome.
- The elevated WBC count can be consistent with infection, but the specific pattern of organ damage and the presence of schistocytes point to a **toxin-mediated microangiopathy** rather than generalized bacteremia-induced DIC.
*Infection with an RNA picornavirus*
- Picornaviruses (e.g., enteroviruses, poliovirus, hepatitis A virus, rhinovirus) can cause various illnesses, including gastroenteritis, but they are not typically associated with the development of **hemolytic uremic syndrome** with its characteristic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
- The diarrheal illness in HUS is most often caused by **Shiga toxin-producing E. coli**, a bacterium, not an RNA picornavirus.
Question 10: A 34-year-old woman comes to the physician because of recent fatigue and weakness that is exacerbated by cross-country skiing. Four weeks ago, she was diagnosed with pneumonia; sputum cultures on Eaton agar showed organisms that lacked a cell wall. Physical examination shows conjunctival pallor and cyanosis of the fingertips. Both lungs are clear to auscultation. Which of the following findings is most likely to confirm the diagnosis?
A. Erythrocytes with denatured hemoglobin inclusions
B. Neutrophils with hypersegmented nuclei
C. Erythrocytes coated with autoantibodies (Correct Answer)
D. Microcytic, hypochromic erythrocytes
E. Erythrocytes with basophilic granules
Explanation: ***Erythrocytes coated with autoantibodies***
- The patient's history of **pneumonia caused by *Mycoplasma pneumoniae*** (lacked a cell wall, grew on Eaton agar) is a classic trigger for **cold agglutinin hemolytic anemia**.
- **Cold agglutinins** are autoantibodies (typically IgM) that bind to red blood cells at colder temperatures, causing **hemolysis** and symptoms like cyanosis of the fingertips and fatigue due to anemia.
*Erythrocytes with denatured hemoglobin inclusions*
- These inclusions, known as **Heinz bodies**, are characteristic of **G6PD deficiency** or other conditions causing **oxidative stress**.
- While they cause hemolytic anemia, the context of *Mycoplasma pneumoniae* infection points away from this diagnosis.
*Neutrophils with hypersegmented nuclei*
- **Hypersegmented neutrophils** are a hallmark feature of **megaloblastic anemias**, such as those caused by **vitamin B12 deficiency** or **folate deficiency**.
- These anemias present with fatigue and weakness, but the history of *Mycoplasma* pneumonia and cyanosis of the fingertips are not typical features.
*Microcytic, hypochromic erythrocytes*
- This morphology is characteristic of **iron deficiency anemia** or **thalassemia**.
- While fatigue and weakness are symptoms, cyanosis of the fingertips and the recent *Mycoplasma* infection do not align with these diagnoses.
*Erythrocytes with basophilic granules*
- **Basophilic stippling** (basophilic granules) in red blood cells is typically seen in **lead poisoning** or **thalassemia**.
- This finding also does not fit the clinical picture of *Mycoplasma pneumoniae*-induced cold agglutinin hemolytic anemia.
