A 55-year-old woman comes to the physician because of a 6-month history of worsening shortness of breath on exertion and fatigue. She has type 1 diabetes mellitus, hypertension, hypercholesterolemia, and chronic kidney disease. Her mother was diagnosed with colon cancer at the age of 65 years. Her blood pressure is 145/92 mm Hg. Examination shows conjunctival pallor. Laboratory studies show: Hemoglobin 9.2 g/dL Mean corpuscular volume 88 μm3 Reticulocyte count 0.6 % Serum Ferritin 145 ng/mL Creatinine 3.1 mg/dL Calcium 8.8 mg/dL A fecal occult blood test is pending. Which of the following is the most likely underlying cause of this patient's symptoms?

Decreased erythropoietin production

Hematopoietic progenitor cell mutation

Autoantibodies against the thyroid gland

A 57-year-old woman comes to the physician because of a 3-month history of easy fatigability and dyspnea on exertion. Menopause occurred 5 years ago. Her pulse is 105/min and blood pressure is 100/70 mm Hg. Physical examination shows pallor of the nail beds and conjunctivae. A peripheral blood smear shows small, pale red blood cells. Further evaluation is most likely to show which of the following findings?

Increased concentration of HbA2

Decreased serum haptoglobin concentration

Increased serum methylmalonic acid concentration

A 55-year-old woman presents with fatigue. She says her symptoms are present throughout the day and gradually started 4 months ago. Her past medical history is significant for rheumatoid arthritis–treated with methotrexate, and diabetes mellitus type 2–treated with metformin. The patient is afebrile, and her vital signs are within normal limits. A physical examination reveals pallor of the mucous membranes. Initial laboratory tests show hemoglobin of 7.9 g/dL, hematocrit of 22%, and mean corpuscular volume of 79 fL. Which of the following is the best next diagnostic step in this patient?

Serum ferritin and soluble transferrin receptor levels

Serum ferritin level and total iron-binding capacity (TIBC)

Serum ferritin and serum iron levels

A 24-year-old Asian woman comes to the office complaining of fatigue. She states that for weeks she has noticed a decrease in her energy. She is a spin instructor, and she has been unable to teach. She said that when she was bringing groceries up the stairs yesterday she experienced some breathlessness and had to rest after ascending 1 flight. She denies chest pain, palpitations, or dyspnea at rest. She has occasional constipation. She recently became vegan 3 months ago following a yoga retreat abroad. The patient has no significant medical history and takes no medications. She was adopted, and her family history is non-contributory. She has never been pregnant. Her last menstrual period was 3 days ago, and her periods are regular. She is sexually active with her boyfriend of 2 years and uses condoms consistently. She drinks a glass of red wine each evening with dinner. She denies tobacco use or other recreational drug use. Her temperature is 99°F (37.2°C), blood pressure is 104/74 mmHg and pulse is 95/min. Oxygen saturation is 98% while breathing ambient air. On physical examination, bilateral conjunctiva are pale. Her capillary refill is 3 seconds. A complete blood count is drawn, as shown below: Hemoglobin: 10 g/dL Hematocrit: 32% Leukocyte count: 10,000/mm^3 with normal differential Platelet count: 200,000/mm^3 A peripheral smear shows hypochromic red blood cells and poikilocytosis. A hemoglobin electrophoresis reveals a minor reduction in hemoglobin A2. Which of the following is most likely to be seen on the patient’s iron studies?

Decreased serum iron and increased TIBC

Normal serum iron and normal TIBC

Increased serum iron and decreased TIBC

Increased serum ferritin and increased iron saturation

Decreased serum iron and decreased TIBC

A 65-year-old man presents to his primary care physician for a yearly checkup. He states he feels he has been in good health other than minor fatigue, which he attributes to aging. The patient has a past medical history of hypertension and is currently taking chlorthalidone. He drinks 1 glass of red wine every night. He has lost 5 pounds since his last appointment 4 months ago. His temperature is 99.2°F (37.3°C), blood pressure is 147/98 mmHg, pulse is 80/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam reveals an obese man in no acute distress. Laboratory values are ordered as seen below. Hemoglobin: 9 g/dL Hematocrit: 27% Mean corpuscular volume: 72 µm^3 Leukocyte count: 6,500/mm^3 with normal differential Platelet count: 193,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 101 mEq/L K+: 4.3 mEq/L HCO3-: 25 mEq/L BUN: 20 mg/dL Glucose: 99 mg/dL Creatinine: 1.1 mg/dL Ca2+: 9.0 mg/dL AST: 32 U/L ALT: 20 U/L 25-OH vitamin D: 15 ng/mL Which of the following is the best next step in management?

Counseling for alcohol cessation

Exercise regimen and weight loss

A 26-year-old woman presents to the clinic today complaining of weakness and fatigue. She is a vegetarian and often struggles to maintain an adequate intake of non-animal based protein. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and she currently denies any illicit drug use. Her past medical history is non-contributory. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 87/min, and respiratory rate 16/min. On physical examination, her pulses are bounding, the complexion is pale, the breath sounds are clear, and the heart sounds are normal. The spleen is mildly enlarged. She is at a healthy body mass index (BMI) of 22 kg/m2. The laboratory results indicate: mean corpuscular volume MCV: 71 fL, Hgb: 11.0, total iron-binding capacity (TIBC): 412 mcg/dL, transferrin saturation (TSAT): 11%. What is the most appropriate treatment for this patient?

Iron replacement for 4–6 months

Lifelong Vitamin B1 supplementation

Lifelong Vitamin B6 supplementation

Iron deficiency anemia for USMLE Step 3: High-Yield Internal Medicine Lessons

Pathophysiology & Etiology - The Rusty Tank Runs Dry

Iron is a critical component of heme synthesis ($Fe^{2+}$ + Protoporphyrin → Heme). Insufficient iron impairs hemoglobin production, leading to microcytic, hypochromic anemia.

📌 Mnemonic LEAD for causes:

Loss of blood (most common)
- Chronic GI bleeding (e.g., PUD, colon cancer) in men & postmenopausal women.
- Menorrhagia in premenopausal women.
Exaggerated demand
- Pregnancy, lactation, adolescent growth spurts.
Absorption poor
- Duodenum is the primary site of absorption.
- Celiac disease, gastrectomy, achlorhydria (e.g., PPI use).
Diet inadequate
- Malnutrition, vegetarian/vegan diets.

Iron absorption pathway in duodenal enterocyte

⭐ Exam Favorite: Plummer-Vinson syndrome is a classic triad of dysphagia (esophageal webs), iron-deficiency anemia, and atrophic glossitis.

Clinical & Diagnosis - Pale, Tired, Spooned Nails

Symptoms: Fatigue, weakness, pallor (especially conjunctival), headache, dyspnea on exertion.
Specific Signs (Classic Triad):
- Koilonychia: Spoon-shaped nails.
- Glossitis: Atrophic, smooth, sore tongue.
- Angular Cheilitis: Fissures at mouth corners.
Pica: Craving for non-nutritive substances like ice (pagophagia), clay, or starch.
**Initial Labs (CBC):
- Microcytic, hypochromic anemia (↓ Hb, ↓ MCV < 80 fL, ↓ MCHC).
- ↑ RDW (Red Cell Distribution Width) is the earliest marker.
Confirmatory Iron Studies:
- ↓ Serum Ferritin (< 30 ng/mL is most specific).
- ↓ Serum Iron.
- ↑ TIBC (Total Iron-Binding Capacity).
- ↓ Transferrin Saturation (< 15%).

⭐ Plummer-Vinson Syndrome: Presents as a triad of dysphagia (due to esophageal webs), iron-deficiency anemia, and glossitis. It carries an increased risk for esophageal squamous cell carcinoma.

Management - Restocking the Iron Store

Oral Iron (First-Line)
- Ferrous Sulfate: Standard dose is 325 mg (65 mg elemental iron) PO TID.
- Administer on an empty stomach or with Vitamin C (ascorbic acid) to ↑ absorption.
- Avoid with antacids, calcium, PPIs, or tetracyclines.
- Side effects: Constipation, black stools, nausea, epigastric distress.
Parenteral Iron (IV/IM)
- Indications: Malabsorption (e.g., celiac, IBD), intolerance to oral Fe, or severe anemia requiring rapid correction.
- Formulations: Iron sucrose, ferric gluconate, iron dextran.
- ⚠️ Iron dextran carries a higher risk of anaphylaxis; a test dose is required.

⭐ Treatment Goal: Continue oral iron for 3-6 months after hemoglobin levels normalize to fully replenish body iron stores (target ferritin >50 ng/mL).

High‑Yield Points - ⚡ Biggest Takeaways

Most common anemia, typically from chronic blood loss (GI bleed, menses) or dietary insufficiency.

Classic signs include pica (ice craving), koilonychia (spoon nails), and atrophic glossitis.

Key lab findings: ↓ ferritin is the most specific marker, ↑ TIBC, ↓ serum iron, and ↑ RDW.

Blood smear reveals microcytic, hypochromic red cells.

Consider Plummer-Vinson syndrome: triad of IDA, dysphagia, and esophageal webs.

In older males/postmenopausal women, exclude GI malignancy as the underlying cause.

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