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PA15.1-3 | Macrocytic Anemias & B12/Folate — Graded Quiz

Graded 12 questions · Untimed · 2 attempts

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Q1 PA15.1 1 pt

A 58-year-old strict vegetarian woman with a 20-year history of well-controlled Hashimoto's thyroiditis presents with 6 months of fatigue, difficulty walking on uneven ground, and tingling in both hands. CBC: Hb 8.4 g/dL, MCV 122 fL. Peripheral smear: macro-ovalocytes, hypersegmented neutrophils (6-lobed). Serum B12 = 58 pg/mL. Serum anti-parietal cell antibodies: positive. Anti-intrinsic factor (anti-IF) antibodies: positive. Which single test result MOST specifically establishes the cause of B12 deficiency in this patient?

A Positive anti-parietal cell antibodies (APCA) — confirms autoimmune gastritis
B Positive anti-intrinsic factor antibodies — the most specific marker of pernicious anaemia
C Low serum B12 (<200 pg/mL) — confirms the deficiency and its cause
D Elevated serum methylmalonic acid — confirms functional B12 deficiency at the cellular level

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Q2 PA15.1 1 pt

A 34-year-old woman at 10 weeks gestation presents for her first antenatal visit. She reports a vegetarian diet and occasional dairy. CBC: Hb 11.4 g/dL, MCV 104 fL. Serum folate: 1.8 ng/mL (low; normal >3.0). Serum B12: 280 pg/mL (borderline). MMA: 0.18 µmol/L (normal <0.4). Homocysteine: 22 µmol/L (elevated; normal <15). She is started on folic acid 5 mg daily. Which ADDITIONAL action is MOST important at this visit?

A Prescribe B12 injections immediately to cover borderline B12 and prevent neural tube defects in the fetus
B Counsel on the folate-only trap: folate supplementation corrects anaemia but will not protect the maternal spinal cord if concurrent B12 deficiency is confirmed on re-testing
C Order a peripheral smear to document macro-ovalocytes before starting therapy
D Withhold folate until B12 status is confirmed, as folate may mask B12 deficiency symptoms and allow neurological deterioration

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Q3 PA15.2 1 pt

A 67-year-old man with known pernicious anaemia stopped his monthly B12 injections 2 years ago after moving abroad. He now presents with progressive lower limb weakness and loss of balance. Examination: vibration sense absent at both ankles and knees, positive Romberg sign, bilateral extensor plantar responses (Babinski positive). Hb 9.8 g/dL, MCV 114 fL. Serum B12 = 42 pg/mL. He is started on B12 injections. After 6 months, his haemoglobin normalises. Which neurological outcome is MOST likely?

A Full neurological recovery expected within 6 months as B12 supplementation reverses all demyelination
B Partial neurological recovery — established axonal degeneration in SCD is irreversible; only demyelination without axonal loss may improve
C No neurological recovery is possible once Babinski sign is present — irreversible upper motor neuron damage has occurred
D Neurological recovery will parallel haematological recovery — once Hb normalises, neurology will also improve fully

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Q4 PA15.2 1 pt

A peripheral blood smear from a 55-year-old patient with MCV 118 fL shows macro-ovalocytes and a neutrophil with 6 nuclear lobes. A second smear from a 60-year-old chronic alcohol user shows large, ROUND macrocytes (not oval), no hypersegmented neutrophils, and normal-looking lymphocytes. Serum B12 and folate are normal in the second patient. Which statement BEST explains why the smear findings differ between these two patients?

A Alcohol causes folate-like deficiency and therefore produces the same macro-ovalocytes as B12 deficiency
B Megaloblastic macrocytosis (DNA synthesis defect) produces macro-ovalocytes + hypersegmented neutrophils; non-megaloblastic macrocytosis (alcohol, liver disease) produces round macrocytes without hypersegmentation
C Neutrophil lobe count does not distinguish megaloblastic from non-megaloblastic macrocytosis — both show hypersegmentation
D Round macrocytes are larger than oval macrocytes and indicate more severe anaemia in alcoholic patients

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Q5 PA15.3 1 pt

A 45-year-old woman with celiac disease presents with fatigue, sore tongue, and peripheral tingling. Labs: Hb 9.1 g/dL, MCV 96 fL (borderline). Peripheral smear: occasional macro-ovalocytes, 2 neutrophils with 5 lobes, 1 neutrophil with 6 lobes out of 100 counted. Serum B12 = 195 pg/mL (borderline low). Serum folate = low. Reticulocyte count = 0.6%. Which smear finding is the EARLIEST and MOST SENSITIVE indicator of megaloblastic change in this patient?

A Occasional macro-ovalocytes — these appear before MCV rises
B Hypersegmented neutrophils (>5-lobed) — they appear before MCV rises and before anaemia becomes severe
C A borderline MCV of 96 fL — already elevated above 80 fL indicates early megaloblastosis
D Low reticulocyte count — this is the first sign of impaired marrow output in megaloblastic anaemia

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Q6 PA15.2 1 pt

A 29-year-old woman with HIV on highly active antiretroviral therapy (HAART) including zidovudine (AZT) for 3 years develops macrocytic anaemia. CBC: Hb 10.2 g/dL, MCV 110 fL. Peripheral smear: round macrocytes. No hypersegmented neutrophils. Serum B12 and folate are both normal. Bone marrow: erythroid hyperplasia with megaloblastic-like changes in some precursors. Which mechanism BEST explains her macrocytosis?

A AZT causes folate trapping by inhibiting dihydrofolate reductase (DHFR), identical to methotrexate
B AZT is a thymidine analogue that inhibits reverse transcriptase but also inhibits mitochondrial DNA polymerase-gamma in erythroid precursors, impairing DNA synthesis and causing megaloblastic-like changes
C HIV itself causes B12 malabsorption from terminal ileal inflammation, producing true B12-deficiency megaloblastosis
D AZT causes haemolysis with reticulocytosis producing round macrocytes from young red cells

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Q7 PA15.1 1 pt

A 70-year-old woman with confirmed pernicious anaemia presents with a 2-month history of diarrhoea, weight loss, and epigastric pain. Her B12 level (on injections) is now 650 pg/mL. Gastroscopy reveals a polypoidal lesion in the gastric fundus. Biopsy shows a well-differentiated neuroendocrine tumour (carcinoid). Which pathophysiological sequence BEST links her pernicious anaemia to this complication?

A Pernicious anaemia → chronic hypergastrinaemia (loss of acid feedback) → sustained gastrin-driven enterochromaffin-like cell hyperplasia → gastric carcinoid
B B12 injections → elevated serum B12 → direct mitogenic effect on fundic mucosa → carcinoid transformation
C Autoimmune gastritis → direct T-cell attack on enterochromaffin-like cells → neoplastic transformation via chronic inflammation
D Anti-parietal cell antibodies cross-react with carcinoid-specific surface antigens → paraneoplastic carcinoid induction

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Q8 PA15.2 1 pt

Two patients have megaloblastic anaemia. Patient A: serum B12 = 95 pg/mL, serum folate = normal, MMA = 0.85 µmol/L (elevated), homocysteine = 38 µmol/L (elevated). Patient B: serum B12 = normal, serum folate = 1.2 ng/mL (low), MMA = 0.19 µmol/L (normal), homocysteine = 31 µmol/L (elevated). A student offers to treat both patients with folic acid 5 mg daily. Which response is MOST appropriate?

A Acceptable for both patients — folate corrects megaloblastosis regardless of the underlying cause
B Acceptable for Patient B only — treating Patient A with folate alone will correct the anaemia but allow subacute combined degeneration to progress
C Unacceptable for both — folate supplementation has no role in megaloblastic anaemia treatment
D Acceptable for Patient A only — B12-deficiency anaemia has a more robust response to folate than folate-deficiency anaemia

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Q9 PA15.1 1 pt

A bone marrow aspirate smear from a 62-year-old woman with confirmed B12 deficiency (serum B12 = 65 pg/mL, Hb 8.2 g/dL, MCV 126 fL) shows: hypercellular marrow, erythroblasts with nuclei 2–3× normal size, lacy/open ('sieve-like') nuclear chromatin, well-haemoglobinised cytoplasm, and large 'giant metamyelocytes' in the granulocyte series. Which cellular process BEST explains the nuclear-cytoplasmic asynchrony?

A B12 deficiency impairs RNA synthesis → cytoplasm cannot produce haemoglobin → nucleus grows without cytoplasmic counterpart
B B12 deficiency impairs thymidylate synthesis → DNA synthesis delayed → nucleus cannot divide while cytoplasm continues to grow and haemoglobinise normally
C B12 deficiency causes accelerated apoptosis of erythroblasts → surviving cells are large due to selection pressure
D B12 deficiency suppresses EPO secretion → fewer erythroblast divisions → cells remain large due to reduced proliferation

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Q10 PA15.1 1 pt

A 52-year-old woman presents with fatigue and mouth soreness. Her CBC: Hb 7.9 g/dL, MCV 108 fL. Peripheral smear shows macro-ovalocytes and neutrophils with 6-lobed and 7-lobed nuclei. Serum B12 = 320 pg/mL (normal >200). Serum folate = normal. MMA = 0.61 µmol/L (elevated). Homocysteine = 29 µmol/L (elevated). Anti-IF antibodies: negative. She does not use alcohol. She is not on any medications. Her diet includes meat, eggs, and dairy. Which is the MOST likely underlying diagnosis?

A Dietary B12 deficiency from inadequate intake despite an animal-product diet
B Food-cobalamin malabsorption — inability to release B12 from food proteins despite adequate intrinsic factor
C Terminal ileal disease causing impaired IF-B12 complex absorption
D Pernicious anaemia — anti-IF antibodies can be falsely negative in up to 50% of cases

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Q11 PA15.3 1 pt

A 38-year-old woman with celiac disease presents with a mixed picture: Hb 9.2 g/dL, MCV 88 fL (normal). Peripheral smear shows a dimorphic red cell population — some microcytic hypochromic cells (target cells, pencil cells) and some macro-ovalocytes — alongside a single neutrophil with 6 lobes. Serum ferritin = 5 ng/mL. Serum B12 = 110 pg/mL (low). The treating physician is puzzled by the normal MCV. Which mechanism BEST explains the normal MCV in the context of dual deficiency?

A Celiac disease preferentially spares B12 absorption — only iron deficiency is present, producing a falsely elevated MCV from reticulocytosis
B Concurrent iron deficiency (microcytic) and B12 deficiency (macrocytic) produce mixed cell populations that average out to a falsely normal MCV on automated analysis
C The automated analyser cannot distinguish between micro- and macrocytes and reports a mean that underestimates both extremes
D Normal MCV confirms that neither iron nor B12 deficiency has yet reached the threshold of affecting RBC size

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Q12 PA15.2 1 pt

A 78-year-old man with Alzheimer's disease is brought by his daughter because of worsening confusion, falls, and 'electric shock' sensations in his legs with neck flexion (L'hermitte's sign). CBC: Hb 10.8 g/dL, MCV 102 fL. Peripheral smear: occasional macro-ovalocytes, 2 neutrophils with 5 lobes out of 100. Serum B12 = 198 pg/mL (borderline). MMA = 0.72 µmol/L (elevated). Homocysteine = 41 µmol/L (elevated). Which is the MOST APPROPRIATE next clinical action?

A Repeat serum B12 in 3 months to confirm true deficiency before starting treatment
B Start intramuscular B12 injections immediately — elevated MMA confirms functional B12 deficiency regardless of borderline serum B12
C Start oral folic acid and observe the haematological response before investigating further
D Arrange MRI brain to exclude multi-infarct dementia before attributing cognitive decline to B12 deficiency

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