Megaloblastic anemias — MCQs

10 questions

A 26-year-old man from India visits the clinic with complaints of feeling tired all the time and experiencing lack of energy for the past couple of weeks. He also complains of weakness and numbness of his lower limbs. He has been strictly vegan since the age of 18, including not consuming eggs and milk. He does not take any vitamin or dietary supplements. Physical examination reveals a smooth, red beefy tongue along with lower extremity sensory and motor deficits. What other finding is most likely to accompany this patient’s condition?

A 28-year-old woman presents with weakness, fatigability, headache, and faintness. She began to develop these symptoms 4 months ago, and their intensity has been increasing since then. Her medical history is significant for epilepsy diagnosed 4 years ago. She was prescribed valproic acid, which, even at a maximum dose, did not control her seizures. She was prescribed phenytoin 6 months ago. Currently, she takes 300 mg of phenytoin sodium daily and is seizure-free. She also takes 40 mg of omeprazole daily for gastroesophageal disease, which was diagnosed 4 months ago. She became a vegan 2 months ago. She does not smoke and consumes alcohol occasionally. Her blood pressure is 105/80 mm Hg, heart rate is 98/min, respiratory rate is 14/min, and temperature is 36.8℃ (98.2℉). Her physical examination is significant only for paleness. Blood test shows the following findings: Erythrocytes 2.5 x 109/mm3 Hb 9.7 g/dL Hct 35% Mean corpuscular hemoglobin 49.9 pg/cell (3.1 fmol/cell) Mean corpuscular volume 136 µm3 (136 fL) Reticulocyte count 0.1% Total leukocyte count 3110/mm3 Neutrophils 52% Lymphocytes 37% Eosinophils 3% Monocytes 8% Basophils 0% Platelet count 203,000/mm3 Which of the following factors most likely caused this patient’s condition?

A 36-year-old woman gravida 5, para 4 was admitted at 31 weeks of gestation with worsening fatigue and shortness of breath on exertion for the past month. She also has nausea and loss of appetite. No significant past medical history. The patient denies any smoking history, alcohol or illicit drug use. Her vital signs include: blood pressure 110/60 mm Hg, pulse 120/min, respiratory rate 22/min and temperature 35.1℃ (97.0℉). A complete blood count reveals a macrocytosis with severe pancytopenia, as follows: Hb 7.2 g/dL RBC 3.6 million/uL WBC 4,400/mm3 Neutrophils 40% Lymphocytes 20% Platelets 15,000/mm3 MCV 104 fL Reticulocytes 0.9% Serum ferritin and vitamin B12 levels were within normal limits. There was an elevated homocysteine level and a normal methylmalonic acid level. Which of the following is the most likely diagnosis in this patient?

A 39-year-old woman presents with progressive weakness, exercise intolerance, and occasional dizziness for the past 3 months. Past medical history is unremarkable. She reports an 18-pack-year smoking history and drinks alcohol rarely. Her vital signs include: temperature 36.6°C (97.8°F), blood pressure 139/82 mm Hg, pulse 98/min. Physical examination is unremarkable. Her laboratory results are significant for the following: Hemoglobin 9.2 g/dL Erythrocyte count 2.1 million/mm3 Mean corpuscular volume (MCV) 88 μm3 Mean corpuscular hemoglobin (MCH) 32 pg/cell Leukocyte count 7,500/mm3 Which of the following is the best next step in the management of this patient’s condition?

A 42-year-old man with a history of tuberculosis presents to your office complaining of fatigue for two months. Serum laboratory studies reveal the following: WBC 7,000 cells/mm^3, Hb 9.0 g/dL, Hct 25%, MCV 88 fL, Platelet 450,000 cells/mm^3, Vitamin B12 500 pg/mL (200-800), and Folic acid 17 ng/mL (2.5-20). Which of the following is the most appropriate next step in the management of anemia in this patient?

A 65-year-old gentleman presents to his primary care physician for difficulties with his gait and recent fatigue. The patient works in a health food store, follows a strict vegan diet, and takes an array of supplements. He noticed that his symptoms have progressed over the past year and decided to see a physician when he found himself feeling abnormally weak on a daily basis in conjunction with his trouble walking. The patient has a past medical history of Crohn's disease, diagnosed in his early 20's, as well as Celiac disease. He states that he has infrequent exacerbations of his Crohn's disease. Recently, the patient has been having worsening bouts of diarrhea that the patient claims is non-bloody. The patient is not currently taking any medications and is currently taking traditional Chinese medicine supplements. Physical exam is notable for 3/5 strength in the upper and lower extremities, absent upper and lower extremity reflexes, and a staggering, unbalanced gait. Laboratory values reveal the following: Serum: Na+: 135 mEq/L Cl-: 100 mEq/L K+: 5.6 mEq/L HCO3-: 22 mEq/L BUN: 27 mg/dL Glucose: 79 mg/dL Creatinine: 1.1 mg/dL Ca2+: 8.4 mg/dL Mg2+: 1.5 mEq/L Leukocyte count and differential: Leukocyte count: 4,522/mm^3 Hemoglobin: 9.2 g/dL Hematocrit: 29% Platelet count: 169,000/mm^3 Reticulocyte count: 2.5% Lactate dehydrogenase: 340 U/L Mean corpuscular volume: 97 fL Which of the following is most likely deficient in this patient?

An 82-year-old woman is brought to the emergency room after her neighbor saw her fall in the hallway. She lives alone and remarks that she has been feeling weak lately. Her diet consists of packaged foods and canned meats. Her temperature is 97.6°F (36.4°C), blood pressure is 133/83 mmHg, pulse is 95/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable for a weak, frail, and pale elderly woman. Laboratory studies are ordered as seen below. Hemoglobin: 9.1 g/dL Hematocrit: 30% Leukocyte count: 6,700/mm^3 with normal differential Platelet count: 199,500/mm^3 MCV: 110 fL Which of the following is the most likely deficiency?

A 68-year-old woman comes to the physician because of increasing heartburn for the last few months. During this period, she has taken ranitidine several times a day without relief and has lost 10 kg (22 lbs). She has retrosternal pressure and burning with every meal. She has had heartburn for several years and took ranitidine as needed. She has hypertension. She has smoked one pack of cigarettes daily for the last 40 years and drinks one glass of wine occasionally. Other current medications include amlodipine and hydrochlorothiazide. She appears pale. Her height is 163 cm (5 ft 4 in), her weight is 75 kg (165 lbs), BMI is 27.5 kg/m2. Her temperature is 37.2°C (98.96°F), pulse is 78/min, and blood pressure is 135/80 mm Hg. Cardiovascular examination shows no abnormalities. Abdominal examination shows mild tenderness to palpation in the epigastric region. Bowel sounds are normal. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 10.2 g/dL Mean corpuscular volume 78 μm Mean corpuscular hemoglobin 23 pg/cell Leukocyte count 9,500/mm3 Platelet count 330,000/mm3 Serum Na+ 137 mEq/L K+ 3.8 mEq/L Cl- 100 mEq/L HCO3- 25 mEq/L Creatinine 1.2 mg/dL Lactate dehydrogenase 260 U/L Alanine aminotransferase 18 U/L Aspartate aminotransferase 15 U/L Lipase (N < 280 U/L) 40 U/L Troponin I (N < 0.1 ng/mL) 0.029 ng/mL An ECG shows normal sinus rhythm without ST-T changes. Which of the following is the most appropriate next step in the management of this patient?

A 76-year-old woman comes in for a routine checkup with her doctor. She is concerned that she feels tired most days and has difficulty doing her household chores. She complains that she gets fatigued and breathless with mild exertion. Past medical history is significant for diabetes mellitus, chronic kidney disease from prolonged elevated blood sugar, and primary biliary cirrhosis. Medications include lisinopril, insulin, and metformin. Family medicine is noncontributory. She drinks one beer every day. Today, she has a heart rate of 98/min, respiratory rate of 17/min, blood pressure of 110/65 mm Hg, and a temperature of 37.0°C (98.6°F). General examination shows that she is pale and haggard looking. She has a heartbeat with a regular rate and rhythm and her lungs are clear to auscultation bilaterally. A complete blood count (CBC) is as follows: Leukocyte count: 12,000/mm3 Red blood cell count: 3.1 million/mm3 Hemoglobin: 11.0 g/dL MCV: 85 fL MCH: 27 pg/cell Platelet count: 450,000/mm3 Fecal occult blood test is negative. What is the most likely cause of her anemia?

Q10

A 25-year-old woman is being evaluated due to complaint of fatigue and voiding pink urine. The laboratory results are as follows: Hb 6.7 Red blood cell count 3.0 x 1012/L Leukocyte count 5,000/mm3 Platelets 170 x 109/L Reticulocyte count 6% Hematocrit 32% The physician thinks that the patient is suffering from an acquired mutation in hematopoietic stem cells, which is confirmed by flow cytometry analysis that revealed these cells are CD 55 and CD 59 negative. However, the physician is interested in knowing the corrected reticulocyte count before starting the patient on eculizumab. What value does the physician find after calculating the corrected reticulocyte count?

Megaloblastic anemias US Medical PG Practice Questions and MCQs

Question 1: A 26-year-old man from India visits the clinic with complaints of feeling tired all the time and experiencing lack of energy for the past couple of weeks. He also complains of weakness and numbness of his lower limbs. He has been strictly vegan since the age of 18, including not consuming eggs and milk. He does not take any vitamin or dietary supplements. Physical examination reveals a smooth, red beefy tongue along with lower extremity sensory and motor deficits. What other finding is most likely to accompany this patient’s condition?

A. Upper limb weakness
B. Psychiatric symptoms
C. Decreased visual acuity
D. Microcytic anemia
E. Ataxia (Correct Answer)

Explanation: **Ataxia** - The patient's history of being a strict vegan, fatigue, weakness, numbness, and neurological deficits (sensory and motor) along with a **smooth, red beefy tongue** are classic signs of **vitamin B12 deficiency**. - **Vitamin B12 deficiency** often leads to **subacute combined degeneration of the spinal cord**, which can manifest as **ataxia**, spasticity, and paresthesias due to demyelination. *Upper limb weakness* - While B12 deficiency can cause generalized weakness, the question specifically highlights **lower extremity sensory and motor deficits**, with **ataxia** being a more characteristic and often earlier neurological sign of spinal cord involvement than upper limb weakness. - Upper limb weakness might develop in advanced stages, but it is not the **most likely** accompanying finding in the early or moderate stages often described with lower limb involvement and ataxia. *Psychiatric symptoms* - **Psychiatric symptoms** such as depression, irritability, and cognitive impairment can occur in **vitamin B12 deficiency**, but **ataxia** is a more direct and common neurological consequence stemming from the demyelination in the spinal cord. - While possible, the question asks for the **most likely** additional finding given the specific neurological presentation. *Decreased visual acuity* - **Optic neuropathy** and **decreased visual acuity** can occur in some cases of **vitamin B12 deficiency**, but it is less common than the spinal cord and peripheral nerve manifestations like ataxia and paresthesias. - The presented symptoms directly point to spinal cord involvement, making **ataxia** a more prominent associated neurological finding. *Microcytic anemia* - **Vitamin B12 deficiency** typically causes **megaloblastic (macrocytic) anemia**, not microcytic anemia. - **Microcytic anemia** is primarily associated with **iron deficiency**, lead poisoning, or thalassemia.

Question 2: A 28-year-old woman presents with weakness, fatigability, headache, and faintness. She began to develop these symptoms 4 months ago, and their intensity has been increasing since then. Her medical history is significant for epilepsy diagnosed 4 years ago. She was prescribed valproic acid, which, even at a maximum dose, did not control her seizures. She was prescribed phenytoin 6 months ago. Currently, she takes 300 mg of phenytoin sodium daily and is seizure-free. She also takes 40 mg of omeprazole daily for gastroesophageal disease, which was diagnosed 4 months ago. She became a vegan 2 months ago. She does not smoke and consumes alcohol occasionally. Her blood pressure is 105/80 mm Hg, heart rate is 98/min, respiratory rate is 14/min, and temperature is 36.8℃ (98.2℉). Her physical examination is significant only for paleness. Blood test shows the following findings: Erythrocytes 2.5 x 109/mm3 Hb 9.7 g/dL Hct 35% Mean corpuscular hemoglobin 49.9 pg/cell (3.1 fmol/cell) Mean corpuscular volume 136 µm3 (136 fL) Reticulocyte count 0.1% Total leukocyte count 3110/mm3 Neutrophils 52% Lymphocytes 37% Eosinophils 3% Monocytes 8% Basophils 0% Platelet count 203,000/mm3 Which of the following factors most likely caused this patient’s condition?

A. Omeprazole intake
B. Alcohol intake
C. Epilepsy
D. Phenytoin intake (Correct Answer)
E. Vegan diet

Explanation: ***Phenytoin intake*** - The patient presents with **macrocytic anemia** (MCV 136 µm3) and **leukopenia** (WBC 3110/mm3), which are characteristic of **folate deficiency**. Phenytoin is a well-established cause of drug-induced folate deficiency, especially with long-term use (patient has been on phenytoin for 6 months). - Phenytoin causes folate deficiency primarily by **inhibiting intestinal folate absorption** and interfering with folate-dependent enzymatic reactions. This leads to impaired DNA synthesis, resulting in megaloblastic anemia and leukopenia. - The timeline fits perfectly: phenytoin started 6 months ago, symptoms began 4 months ago, allowing time for folate stores to deplete. *Incorrect: Omeprazole intake* - Omeprazole is a **proton pump inhibitor** that can impair the absorption of **vitamin B12** due to reduced gastric acid, which is needed to cleave B12 from dietary proteins. - While vitamin B12 deficiency can also cause macrocytic anemia, it typically takes **years** to develop after the onset of malabsorption (the patient has only been on omeprazole for 4 months). Additionally, B12 deficiency does not typically cause the degree of leukopenia seen here. *Incorrect: Alcohol intake* - **Chronic alcohol abuse** can cause macrocytic anemia through multiple mechanisms: direct bone marrow toxicity, folate deficiency (poor intake and absorption), and liver disease. - However, the patient reports only **occasional alcohol consumption**, making this an unlikely primary cause. Alcohol-related folate deficiency requires chronic heavy use. *Incorrect: Epilepsy* - Epilepsy itself is **not directly associated** with macrocytic anemia or leukopenia. - The hematologic abnormalities are due to the **antiepileptic medication** (phenytoin) rather than the neurological condition itself. *Incorrect: Vegan diet* - A **vegan diet** is a common cause of **vitamin B12 deficiency** since B12 is primarily found in animal products (meat, dairy, eggs). - However, the patient became vegan only **2 months ago**. The body has substantial B12 stores (in the liver) that typically last **3-5 years** before deficiency develops. This timeline is too short to explain the current presentation. Additionally, B12 deficiency alone does not typically cause significant leukopenia as seen here.

Question 3: A 36-year-old woman gravida 5, para 4 was admitted at 31 weeks of gestation with worsening fatigue and shortness of breath on exertion for the past month. She also has nausea and loss of appetite. No significant past medical history. The patient denies any smoking history, alcohol or illicit drug use. Her vital signs include: blood pressure 110/60 mm Hg, pulse 120/min, respiratory rate 22/min and temperature 35.1℃ (97.0℉). A complete blood count reveals a macrocytosis with severe pancytopenia, as follows: Hb 7.2 g/dL RBC 3.6 million/uL WBC 4,400/mm3 Neutrophils 40% Lymphocytes 20% Platelets 15,000/mm3 MCV 104 fL Reticulocytes 0.9% Serum ferritin and vitamin B12 levels were within normal limits. There was an elevated homocysteine level and a normal methylmalonic acid level. Which of the following is the most likely diagnosis in this patient?

A. Normal pregnancy
B. Aplastic anemia
C. Vitamin B12 deficiency
D. Iron deficiency anemia
E. Folate deficiency (Correct Answer)

Explanation: ***Folate deficiency*** - The patient presents with **macrocytic anemia** (MCV 104 fL), **pancytopenia**, and symptoms of severe anemia. The elevated **homocysteine** and normal **methylmalonic acid** levels are classic indicators of folate deficiency, as folate is required to convert homocysteine to methionine but not for MMA metabolism. - Her status as **gravida 5, para 4** in the **third trimester** (31 weeks) significantly increases her risk for folate deficiency due to high fetal demands, even without poor nutritional intake. *Normal pregnancy* - While **fatigue and shortness of breath** are common in pregnancy, severe **pancytopenia** and **macrocytosis (MCV 104)** are not normal physiological changes. - Hemoglobin of 7.2 g/dL indicates severe anemia, far below the expected physiological decrease in Hb during pregnancy due to **hemodilution**. *Aplastic anemia* - Aplastic anemia is characterized by **pancytopenia** but typically presents with **normocytic or mildly macrocytic RBCs**, and there would be severe **reticulocytopenia** (which is present here, 0.9%). - However, the distinct biochemical markers of elevated **homocysteine** and normal **methylmalonic acid** point more specifically towards a nutritional deficiency rather than bone marrow failure. *Vitamin B12 deficiency* - **Vitamin B12 deficiency** also causes **macrocytic anemia** and **pancytopenia**, with elevated **homocysteine levels**. - However, a key differentiating factor is that **methylmalonic acid (MMA)** levels would also be **elevated** in B12 deficiency, which is normal in this patient. *Iron deficiency anemia* - **Iron deficiency anemia** is typically characterized by **microcytic, hypochromic** red blood cells (low MCV), not macrocytic. - While it can cause fatigue and shortness of breath, the laboratory findings of a **normal ferritin** (suggesting adequate iron stores), **macrocytosis**, and **pancytopenia** do not fit with iron deficiency.

Question 4: A 39-year-old woman presents with progressive weakness, exercise intolerance, and occasional dizziness for the past 3 months. Past medical history is unremarkable. She reports an 18-pack-year smoking history and drinks alcohol rarely. Her vital signs include: temperature 36.6°C (97.8°F), blood pressure 139/82 mm Hg, pulse 98/min. Physical examination is unremarkable. Her laboratory results are significant for the following: Hemoglobin 9.2 g/dL Erythrocyte count 2.1 million/mm3 Mean corpuscular volume (MCV) 88 μm3 Mean corpuscular hemoglobin (MCH) 32 pg/cell Leukocyte count 7,500/mm3 Which of the following is the best next step in the management of this patient’s condition?

A. Serum ferritin level
B. Direct antiglobulin test
C. C-reactive protein (CRP)
D. Bone marrow biopsy
E. Reticulocyte count (Correct Answer)

Explanation: ***Reticulocyte count*** - A **normocytic anemia** (MCV 88) with signs of weakness and exercise intolerance requires evaluation of **red blood cell production**. - A reticulocyte count helps differentiate between **hypoproliferative** (low count) and **hyperproliferative** (high count) anemias, guiding further diagnostic steps. *Serum ferritin level* - While often low in **iron-deficiency anemia**, this patient’s **normocytic MCV** makes iron deficiency less likely as the primary cause without other features. - A normal ferritin doesn't rule out other causes of anemia, and a high ferritin could indicate **anemia of chronic disease**, but further understanding of RBC production is needed first. *Direct antiglobulin test* - This test is used to diagnose **autoimmune hemolytic anemia**, which typically presents with **jaundice**, **splenomegaly**, and elevated **lactate dehydrogenase (LDH)**, none of which are noted here. - While anemia can result from hemolysis, the initial presentation doesn't strongly suggest an immune-mediated destruction process, and determining the bone marrow's response is more immediate. *C-reactive protein (CRP)* - CRP is a marker of **inflammation**, and elevated levels could suggest **anemia of chronic disease**. - However, knowing the **reticulocyte count** will provide more direct information about bone marrow function, which is crucial for characterizing the anemia. *Bone marrow biopsy* - A bone marrow biopsy is an **invasive procedure** typically reserved for complex anemias where initial, less invasive tests have failed to provide a diagnosis or when conditions like **aplastic anemia** or **myelodysplastic syndromes** are strongly suspected. - It is not the appropriate **first diagnostic step** in evaluating an undifferentiated normocytic anemia like this.

Question 5: A 42-year-old man with a history of tuberculosis presents to your office complaining of fatigue for two months. Serum laboratory studies reveal the following: WBC 7,000 cells/mm^3, Hb 9.0 g/dL, Hct 25%, MCV 88 fL, Platelet 450,000 cells/mm^3, Vitamin B12 500 pg/mL (200-800), and Folic acid 17 ng/mL (2.5-20). Which of the following is the most appropriate next step in the management of anemia in this patient?

A. Iron studies (Correct Answer)
B. Bone marrow biopsy
C. Observation
D. Colonoscopy
E. Erythropoietin administration

Explanation: ***Iron studies*** - The patient has **normocytic anemia** (MCV 88 fL) and a history of **tuberculosis**, which is a chronic inflammatory condition often associated with **anemia of chronic disease (ACD)**. - **Iron studies** are critical to differentiate between **ACD** (typically high ferritin, low transferrin saturation) and iron deficiency anemia, which can coexist. *Bone marrow biopsy* - A **bone marrow biopsy** is an invasive procedure and is typically reserved for cases of unexplained severe anemia, pancytopenia, or suspicion of primary bone marrow disorders that are not suggested by the current findings. - The current blood counts do not indicate an urgent need for bone marrow evaluation, as the **anemia is mild to moderate**, and other cell lines are normal (WBC) or elevated (platelets). *Erythropoietin administration* - **Erythropoietin administration** is used in specific anemias, such as **anemia of chronic kidney disease** or certain types of myelodysplastic syndromes. - It is not the initial step for diagnosing and managing anemia in a patient with a chronic inflammatory condition like tuberculosis without first assessing iron status or ruling out other treatable causes. *Observation* - **Observation** is inappropriate given the patient's symptomatic anemia (fatigue) and the identified abnormalities (Hb 9.0 g/dL). - Anemia warrants investigation to identify its cause and provide appropriate treatment, especially in the context of a chronic illness like tuberculosis. *Colonoscopy* - A **colonoscopy** is indicated if there is suspicion of **gastrointestinal blood loss**, which typically presents with **microcytic anemia** (low MCV) due to chronic iron deficiency. - This patient has **normocytic anemia**, and there are no symptoms suggestive of GI bleeding, making colonoscopy not the most appropriate first step.

Question 6: A 65-year-old gentleman presents to his primary care physician for difficulties with his gait and recent fatigue. The patient works in a health food store, follows a strict vegan diet, and takes an array of supplements. He noticed that his symptoms have progressed over the past year and decided to see a physician when he found himself feeling abnormally weak on a daily basis in conjunction with his trouble walking. The patient has a past medical history of Crohn's disease, diagnosed in his early 20's, as well as Celiac disease. He states that he has infrequent exacerbations of his Crohn's disease. Recently, the patient has been having worsening bouts of diarrhea that the patient claims is non-bloody. The patient is not currently taking any medications and is currently taking traditional Chinese medicine supplements. Physical exam is notable for 3/5 strength in the upper and lower extremities, absent upper and lower extremity reflexes, and a staggering, unbalanced gait. Laboratory values reveal the following: Serum: Na+: 135 mEq/L Cl-: 100 mEq/L K+: 5.6 mEq/L HCO3-: 22 mEq/L BUN: 27 mg/dL Glucose: 79 mg/dL Creatinine: 1.1 mg/dL Ca2+: 8.4 mg/dL Mg2+: 1.5 mEq/L Leukocyte count and differential: Leukocyte count: 4,522/mm^3 Hemoglobin: 9.2 g/dL Hematocrit: 29% Platelet count: 169,000/mm^3 Reticulocyte count: 2.5% Lactate dehydrogenase: 340 U/L Mean corpuscular volume: 97 fL Which of the following is most likely deficient in this patient?

A. Vitamin D
B. Iron
C. Vitamin B9
D. Vitamin E
E. Vitamin B12 (Correct Answer)

Explanation: ***Vitamin B12*** - The patient's **vegan diet**, history of **Crohn's disease**, **Celiac disease**, and **diarrhea** all increase the risk of **vitamin B12 malabsorption**. - **Neurological symptoms** like gait difficulties, weakness, and absent reflexes are characteristic of **vitamin B12 deficiency**, which can also cause **anemia** with a **normal MCV** (masked by co-existing iron deficiency or thalassemia trait). *Vitamin D* - While common in patients with malabsorption conditions like Crohn's disease and Celiac disease, **vitamin D deficiency** primarily presents with **bone pain**, **muscle weakness**, and **osteoporosis**, not the prominent neurological findings seen here. - The patient's **calcium level (8.4 mg/dL)** is at the lower end of normal, but not overtly hypocalcemic, which would be expected with severe vitamin D deficiency. *Iron* - **Iron deficiency** is common in Crohn's and Celiac disease due to malabsorption and chronic blood loss, leading to **microcytic anemia** and **fatigue**. - However, the patient's **MCV is normal (97 fL)**, and iron deficiency does not typically explain the **neurological symptoms** (gait difficulties, absent reflexes) described. *Vitamin B9* - **Folate deficiency** can cause **megaloblastic anemia** and fatigue, similar to vitamin B12 deficiency, but it is less likely to cause the **severe neurological symptoms** seen here. - While malabsorption conditions can affect folate, the specific neurological presentation points more strongly towards B12. *Vitamin E* - **Vitamin E deficiency** can cause **neurological symptoms** such as ataxia, peripheral neuropathy, and muscle weakness due to its role as an antioxidant. - However, deficiency is rare in adults and usually severe malabsorption of fats from conditions like abetalipoproteinemia. While Crohn's and Celiac can cause fat malabsorption, the constellation of symptoms, including anemia and masked MCV, aligns more directly with B12.

Question 7: An 82-year-old woman is brought to the emergency room after her neighbor saw her fall in the hallway. She lives alone and remarks that she has been feeling weak lately. Her diet consists of packaged foods and canned meats. Her temperature is 97.6°F (36.4°C), blood pressure is 133/83 mmHg, pulse is 95/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable for a weak, frail, and pale elderly woman. Laboratory studies are ordered as seen below. Hemoglobin: 9.1 g/dL Hematocrit: 30% Leukocyte count: 6,700/mm^3 with normal differential Platelet count: 199,500/mm^3 MCV: 110 fL Which of the following is the most likely deficiency?

A. Zinc
B. Vitamin B12
C. Thiamine
D. Niacin
E. Folate (Correct Answer)

Explanation: ***Folate*** - The patient's **macrocytic anemia** (MCV 110 fL, hemoglobin 9.1 g/dL) combined with a diet of **packaged foods and canned meats** with **no fresh fruits or vegetables** strongly suggests folate deficiency. - **Folate is found exclusively in fresh produce** (leafy greens, fruits, legumes), which is completely absent from this patient's diet. - **Elderly individuals** living alone with inadequate nutrition are at particularly high risk for **folate deficiency**. *Vitamin B12* - While vitamin B12 deficiency also causes **macrocytic anemia**, her diet includes **canned meats which retain B12** (heat-stable vitamin). - B12 deficiency typically requires years to develop due to large hepatic stores, and often presents with **neurological manifestations** (subacute combined degeneration, peripheral neuropathy), which are absent here. - The dietary pattern makes folate deficiency more likely than B12 deficiency. *Zinc* - Zinc deficiency causes impaired immune function, delayed wound healing, skin lesions, and **taste disturbances**, but **not macrocytic anemia**. - No clinical or laboratory findings suggest zinc deficiency. *Thiamine* - Thiamine (vitamin B1) deficiency causes **Wernicke-Korsakoff syndrome** or **beriberi** (wet or dry), presenting with neurological symptoms, heart failure, or peripheral neuropathy. - Thiamine deficiency does **not cause macrocytic anemia**. *Niacin* - Niacin (vitamin B3) deficiency causes **pellagra**, characterized by the \"3 D's\": **dermatitis, diarrhea, and dementia**. - Niacin deficiency is **not associated with macrocytic anemia**.

Question 8: A 68-year-old woman comes to the physician because of increasing heartburn for the last few months. During this period, she has taken ranitidine several times a day without relief and has lost 10 kg (22 lbs). She has retrosternal pressure and burning with every meal. She has had heartburn for several years and took ranitidine as needed. She has hypertension. She has smoked one pack of cigarettes daily for the last 40 years and drinks one glass of wine occasionally. Other current medications include amlodipine and hydrochlorothiazide. She appears pale. Her height is 163 cm (5 ft 4 in), her weight is 75 kg (165 lbs), BMI is 27.5 kg/m2. Her temperature is 37.2°C (98.96°F), pulse is 78/min, and blood pressure is 135/80 mm Hg. Cardiovascular examination shows no abnormalities. Abdominal examination shows mild tenderness to palpation in the epigastric region. Bowel sounds are normal. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 10.2 g/dL Mean corpuscular volume 78 μm Mean corpuscular hemoglobin 23 pg/cell Leukocyte count 9,500/mm3 Platelet count 330,000/mm3 Serum Na+ 137 mEq/L K+ 3.8 mEq/L Cl- 100 mEq/L HCO3- 25 mEq/L Creatinine 1.2 mg/dL Lactate dehydrogenase 260 U/L Alanine aminotransferase 18 U/L Aspartate aminotransferase 15 U/L Lipase (N < 280 U/L) 40 U/L Troponin I (N < 0.1 ng/mL) 0.029 ng/mL An ECG shows normal sinus rhythm without ST-T changes. Which of the following is the most appropriate next step in the management of this patient?

A. 24-hour esophageal pH monitoring
B. Esophagogastroduodenoscopy (Correct Answer)
C. Barium swallow
D. Trial of proton-pump inhibitor
E. Esophageal manometry

Explanation: ***Esophagogastroduodenoscopy*** - This patient presents with **alarm symptoms** (weight loss, iron deficiency anemia, persistent heartburn unresponsive to ranitidine) that warrant an immediate investigation for underlying malignancy or severe mucosal damage. - **EGD directly visualizes the esophagus, stomach, and duodenum**, allowing for biopsies of suspicious lesions, which is crucial given her risk factors (smoking, chronic GERD, age). *24-hour esophageal pH monitoring* - This test is primarily used to **diagnose GERD** in patients with typical symptoms but normal endoscopy, or to guide treatment for refractory GERD. - It is not the appropriate first step here because the patient has alarm symptoms, which necessitate direct visualization and biopsy to rule out serious pathology. *Barium swallow* - A barium swallow can identify **structural abnormalities** such as strictures, diverticula, or large masses but has limited utility for detecting subtle mucosal changes or early malignancy. - It does not allow for **biopsy**, which is essential for definitive diagnosis in a patient with alarm symptoms. *Trial of proton-pump inhibitor* - A trial of PPIs is appropriate for patients with **typical GERD symptoms** without alarm features, as a diagnostic and therapeutic intervention. - However, this patient has already tried ranitidine (an H2 blocker) without relief and exhibits multiple **alarm symptoms**, making empirical treatment insufficient and potentially dangerous by delaying diagnosis. *Esophageal manometry* - Esophageal manometry assesses **esophageal motility** and sphincter function, useful for diagnosing motility disorders like achalasia or diffuse esophageal spasm. - It is indicated if a motility disorder is suspected, usually *after* ruling out structural causes with EGD, and does not address the immediate concern of underlying malignancy or severe damage raised by the patient's alarm symptoms.

Question 9: A 76-year-old woman comes in for a routine checkup with her doctor. She is concerned that she feels tired most days and has difficulty doing her household chores. She complains that she gets fatigued and breathless with mild exertion. Past medical history is significant for diabetes mellitus, chronic kidney disease from prolonged elevated blood sugar, and primary biliary cirrhosis. Medications include lisinopril, insulin, and metformin. Family medicine is noncontributory. She drinks one beer every day. Today, she has a heart rate of 98/min, respiratory rate of 17/min, blood pressure of 110/65 mm Hg, and a temperature of 37.0°C (98.6°F). General examination shows that she is pale and haggard looking. She has a heartbeat with a regular rate and rhythm and her lungs are clear to auscultation bilaterally. A complete blood count (CBC) is as follows: Leukocyte count: 12,000/mm3 Red blood cell count: 3.1 million/mm3 Hemoglobin: 11.0 g/dL MCV: 85 fL MCH: 27 pg/cell Platelet count: 450,000/mm3 Fecal occult blood test is negative. What is the most likely cause of her anemia?

A. Chronic kidney disease (Correct Answer)
B. Acute bleeding
C. Alcoholism
D. Liver disease
E. Colorectal cancer

Explanation: ***Chronic kidney disease*** - **Chronic kidney disease (CKD)** is a common cause of **normocytic, normochromic anemia** due to decreased production of **erythropoietin** by the kidneys. - This patient's history of CKD, alongside her **normocytic anemia (MCV 85 fL)**, makes this the most likely cause. *Acute bleeding* - Acute bleeding would typically present with signs of **hypovolemia** (e.g., hypotension, tachycardia) and potentially a **reticulocytosis** as the bone marrow compensates, neither of which are seen here. - The **negative fecal occult blood test** and stable vital signs also argue against acute or chronic gastrointestinal bleeding. *Alcoholism* - Chronic alcoholism can lead to anemia, often **macrocytic** due to **folate deficiency**, or less commonly microcytic if associated with iron deficiency from GI bleeding. - While she drinks one beer daily, this amount is unlikely to directly cause significant anemia, especially given her **normocytic MCV**. *Liver disease* - **Primary biliary cirrhosis (PBC)** can cause anemia through various mechanisms, including **hemolysis**, **folate deficiency**, or bleeding from **portal hypertension**. - However, PBC-related anemia is often microcytic or macrocytic, and her **normocytic MCV** and the more direct link to CKD make it less likely to be the primary cause. *Colorectal cancer* - **Colorectal cancer** can cause anemia due to **chronic blood loss**, which would typically lead to **iron deficiency anemia** (microcytic anemia). - The patient has a **normocytic anemia (MCV 85 fL)** and a **negative fecal occult blood test**, making this diagnosis highly unlikely.

Question 10: A 25-year-old woman is being evaluated due to complaint of fatigue and voiding pink urine. The laboratory results are as follows: Hb 6.7 Red blood cell count 3.0 x 1012/L Leukocyte count 5,000/mm3 Platelets 170 x 109/L Reticulocyte count 6% Hematocrit 32% The physician thinks that the patient is suffering from an acquired mutation in hematopoietic stem cells, which is confirmed by flow cytometry analysis that revealed these cells are CD 55 and CD 59 negative. However, the physician is interested in knowing the corrected reticulocyte count before starting the patient on eculizumab. What value does the physician find after calculating the corrected reticulocyte count?

A. 3.1%
B. 0.4%
C. 0.1%
D. 0.6%
E. 4.6% (Correct Answer)

Explanation: ***4.6%*** - The corrected reticulocyte count accounts for the degree of anemia by adjusting for the patient's hematocrit compared to normal. - **Formula: Corrected Retics% = Observed Retics% × (Patient's Hct / Normal Hct)** - Using normal Hct of 42% for women: 6% × (32/42) = 6% × 0.76 = **4.56% ≈ 4.6%** - This reflects the actual reticulocyte production capacity adjusted for the anemic state. *3.1%* - This value might result from using an incorrect normal hematocrit value in the calculation. - For example, using 6% × (32/60) would give approximately 3.2%, suggesting use of an inappropriately high reference value. *0.4%* - This value likely results from applying the **Reticulocyte Production Index (RPI)** formula, which includes a maturation factor correction: 6% × (32/42) × (1/2.5) = 1.82%, then with further error. - Such a low value from formula misapplication does not represent the standard corrected reticulocyte count requested. *0.1%* - This extremely low value would indicate **severe calculation error** or bone marrow failure, which contradicts the observed 6% reticulocyte count. - In PNH with hemolysis, reticulocyte production is typically increased, making this value implausible. *0.6%* - This incorrect value could result from mathematical errors in applying correction factors or using the wrong hematocrit values in the formula. - The standard corrected reticulocyte formula would not yield this value with the given parameters.

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