A 56-year-old man with a 10-year history of type 2 diabetes mellitus comes to the emergency

department because of a painful, swollen left foot. He says the symptoms began 3 days ago
after he accidentally stepped on a nail but did not seek medical attention. Physical examination
shows a swollen, erythematous left foot with a purulent ulcer at the plantar surface and
surrounding warmth. His temperature is 38.7°C (101.7°F), pulse is 103/min, and blood pressure
is 128/76 mm Hg. Laboratory studies show:

● WBC count: 15,200/mm³ (normal: 4,000–11,000/mm³)

● Glucose: 298 mg/dL (normal: 70–100 mg/dL)

● HbA1c: 9.3% (normal: <5.7%)

Which of the following changes in immune function is most likely contributing to this patient’s
condition?

(A) Decreased activation of NADPH oxidase in neutrophils

(B) Decreased function of macrophage major histocompatibility complex II expression
(C) Impaired chemotaxis of neutrophils
(D) Impaired B-cell isotype switching
(E) Inhibited generation of membrane attack complex (MAC)
A 6-year-old girl is brought to the pediatrician because of a 2-day history of easy bruising and
bleeding gums. Her parents state she had an upper respiratory infection 1 week ago but has
otherwise been healthy. She is not taking any medications. Physical examination shows
scattered petechiae over her lower extremities and mild gingival bleeding. There is no
lymphadenopathy or hepatosplenomegaly. Laboratory studies show:

● Hemoglobin: 12.4 g/dL (normal: 11.5–15.5 g/dL)

● WBC count: 7,800/mm³ (normal: 4,500–11,000/mm³)

● Platelet count: 18,000/mm³ (normal: 150,000–450,000/mm³)

● PT: 12 seconds (normal: 11–14)

● aPTT: 30 seconds (normal: 25–35)

A peripheral blood smear shows decreased platelets with otherwise normal morphology. Which
of the following immune mechanisms is most likely responsible for this patient’s condition?

(A) Antibody-mediated destruction of platelets in the spleen

(B) Autoantibody binding to clotting factor VIII
(C) Defective platelet adhesion to subendothelium
(D) Immune complex deposition in small vessels
(E) Macrophage activation via IFN-γ
A 62-year-old man with a history of poorly controlled type 2 diabetes mellitus presents with
progressive fatigue and unintentional weight loss over the past 3 months. He reports taking
metformin irregularly and has not seen a physician in over a year. Physical examination shows
dry mucous membranes and mild peripheral edema. His BMI is 33 kg/m². Laboratory studies
show:

● Blood glucose: 286 mg/dL

● HbA1c: 10.2%

● Serum creatinine: 2.1 mg/dL

● Urinalysis: +2 protein, no hematuria

A kidney biopsy is performed, and histopathology shows amorphous, eosinophilic extracellular

material in the mesangium that stains positively with Congo red and exhibits apple-green
birefringence under polarized light. Which of the following best describes the origin of the
substance found in this patient's kidney?

(A) Excess immunoglobulin light chains from plasma cells

(B) Misfolded transthyretin protein from the liver
(C) A product secreted by pancreatic beta cells
(D) Chronic immune complex deposition
(E) Apoptotic cellular debris from glomerular endothelial cells
A 72-year-old man is brought to the emergency department 2 hours after the sudden onset of
left-sided weakness and slurred speech. His past medical history includes hypertension,
hyperlipidemia, and atrial fibrillation. He has been nonadherent to his medications, including
warfarin, due to frequent INR checks. A CT scan of the head shows an evolving right middle
cerebral artery infarct with no evidence of hemorrhage.

He is admitted and started on dual antiplatelet therapy. Over the next 48 hours, his condition
deteriorates. Repeat imaging shows an expanding infarct with cytotoxic edema and disruption of
the blood-brain barrier. Microscopic examination of the affected brain tissue would most likely
show evidence of which of the following processes?

(A) Liquefactive necrosis due to lysosomal enzyme release

(B) Caseous necrosis mediated by granulomatous inflammation
(C) Apoptotic cell death due to DNA fragmentation
(D) Fat necrosis due to enzymatic digestion
(E) Coagulative necrosis with cell outlines preserved initially
A 54-year-old man with poorly controlled type 2 diabetes mellitus comes to the clinic for
follow-up. He has not been taking his medications regularly. Physical examination shows
decreased sensation in a stocking-glove pattern and decreased vibratory sense in the lower
extremities. His HbA1c is 10.1% (normal: <5.7%). A renal biopsy is obtained and shows diffuse
thickening of the glomerular basement membrane and increased mesangial matrix deposition.
Electron microscopy shows effacement of podocyte foot processes.

Which of the following adaptive or pathologic cellular processes most likely contributes to this
patient's renal findings?

(A) Apoptosis
(B) Coagulative necrosis
(C) Hyperplasia
(D) Hyaline arteriolosclerosis
(E) Amyloid deposition
A 6-year-old boy is brought to the emergency department by his parents due to persistent
bleeding after a minor fall during a soccer game. His gums have also been bleeding easily for
the past few weeks, and his mother notes he has had frequent nosebleeds. There is no family
history of bleeding disorders. Physical examination reveals scattered petechiae and
ecchymoses on the lower extremities. Laboratory studies show:

● Hemoglobin: 12.8 g/dL (normal: 11.5–15.5)

● Platelet count: 28,000/mm³ (normal: 150,000–450,000)

● Bleeding time: Prolonged

● PT: Normal

● aPTT: Normal

Which of the following is the most likely underlying mechanism responsible for this patient's
condition?

(A) Deficiency of von Willebrand factor

(B) Platelet glycoprotein Ib receptor deficiency
(C) Autoantibody-mediated platelet destruction
(D) Factor VIII deficiency
(E) Deficiency of tissue factor production
A 58-year-old man comes to the clinic for routine follow-up. He has a 10-year history of poorly
controlled type 2 diabetes mellitus and has been noncompliant with his medications. His most
recent HbA1c is 10.2% (normal: <5.7%). Funduscopic examination shows microaneurysms and
dot-blot hemorrhages. Urinalysis reveals 1+ proteinuria. A biopsy of the kidney is performed and
shows glomerular basement membrane thickening with eosinophilic nodular deposits in the
mesangium that are PAS-positive and Congo red-positive.

Which of the following is the most likely mechanism contributing to this patient’s renal findings?

(A) Deposition of oxidized LDL in the glomeruli

(B) Endothelial damage from free radical generation
(C) Immune complex deposition
(D) Non-enzymatic glycosylation of basement membranes
(E) T-cell mediated cytotoxicity
A 65-year-old man comes to the emergency department because of black tarry stools for 2
days. He has a history of coronary artery disease and had a drug-eluting stent placed 6 months
ago. Medications include metoprolol, atorvastatin, and two antiplatelet agents. On physical
exam, he appears pale. Digital rectal exam reveals melena. Laboratory studies show:

● Hemoglobin: 8.6 g/dL (13.5–17.5 g/dL)

● Platelet count: 220,000/mm³ (150,000–450,000/mm³)

● PT: 12 sec (normal: 11–15 sec)

● aPTT: 29 sec (normal: 25–35 sec)

● Bleeding time: Prolonged

Which of the following medications is most likely responsible for the bleeding in this patient?

(A) Apixaban
(B) Heparin
(C) Aspirin
(D) Warfarin
(E) Dabigatran
A 50-year-old woman with a history of type 2 diabetes mellitus and obesity presents with
acute left leg swelling and pain. She has had difficulty controlling her blood sugar and is on
insulin therapy. Physical exam reveals a warm, erythematous left calf with tenderness to
palpation. Ultrasound confirms the presence of a deep vein thrombosis (DVT). Laboratory
studies show:

● HbA1c: 8.7% (normal: <5.7%)

● Fasting glucose: 220 mg/dL (normal: 70–100 mg/dL)

● Platelet count: 400,000/mm³ (normal: 150,000–450,000/mm³)

● PT: 13 sec (normal: 11–15 sec)

● aPTT: 30 sec (normal: 25–35 sec)

● D-dimer: Elevated

Which of the following mechanisms is most likely contributing to this patient's risk of developing
deep vein thrombosis?

(A) Increased insulin levels promoting procoagulant factors

(B) Increased fibrinolysis secondary to elevated glucose levels
(C) Hyperglycemia causing endothelial dysfunction
(D) Impaired platelet aggregation from insulin therapy
(E) Excessive antithrombin III production
A 62-year-old woman with a history of type 2 diabetes mellitus, hypertension, and
hyperlipidemia presents to the emergency department with sharp chest pain radiating to her
left arm. She has been experiencing intermittent chest pain for the past few days but thought it
was related to heartburn. On examination, her blood pressure is 160/95 mm Hg, heart rate is
95/min, and temperature is 37°C (98.6°F). An ECG shows ST-segment elevations in leads
V2-V4, and cardiac biomarkers are elevated. She is started on antiplatelet therapy.

Laboratory findings include:

● Platelet count: 350,000/mm³ (normal: 150,000–450,000/mm³)

● Fibrinogen: 450 mg/dL (normal: 200–400 mg/dL)

● PT: 12 sec (normal: 11–15 sec)

● aPTT: 30 sec (normal: 25–35 sec)

Which of the following is most likely responsible for the increased risk of this patient’s coronary
event?

(A) Increased platelet aggregation and activation due to hyperglycemia

(B) Impaired fibrinolysis caused by insulin resistance
(C) Increased levels of tPA leading to clot breakdown
(D) Overproduction of prostacyclin reducing platelet aggregation
(E) Elevated fibrinogen levels contributing to clot stability