A 35-year-old woman comes to the physician because of a 1-day history of swelling and pain in the left leg. Two days ago, she returned from a business trip on a long-distance flight. She has alcohol use disorder. Physical examination shows a tender, swollen, and warm left calf. Serum studies show an increased homocysteine concentration and a methylmalonic acid concentration within the reference range. Further evaluation of this patient is most likely to show which of the following serum findings?

Decreased cobalamin concentration

Decreased protein C concentration

Increased fibrinogen concentration

Increased pyridoxine concentration

A 60-year-old woman presents to the physician because of shortness of breath and easy fatigability over the past 3 months. Her symptoms become worse with physical activity. She notes no chest pain, cough, or wheezing. Her last menstrual period was 10 years ago. She currently takes calcium and vitamin D supplements as well as a vaginal estrogen cream. For several years, her diet has been poor, as she often does not feel like eating. The patient’s medical history is otherwise unremarkable. She works as a piano teacher at the local community center. She does not use tobacco or illicit drugs and enjoys an occasional glass of red wine with dinner. Her vital signs include: pulse 100/min, respiratory rate 16/min, and blood pressure 140/84 mm Hg. Physical examination reveals impaired vibratory sensation in the legs. Pallor is evident on her hands. Which of the following laboratory tests is expected to be abnormal in this patient?

Erythrocyte pyruvate kinase activity

Erythrocyte glutathione reductase activity

A 58-year-old man presents to the Emergency Department after 3 hours of intense suprapubic pain associated with inability to urinate for the past day or two. His medical history is relevant for benign prostatic hyperplasia (BPH) that has been under treatment with prazosin and tadalafil. Upon admission, he is found to have a blood pressure of 180/100 mm Hg, a pulse of 80/min, a respiratory rate of 23/min, and a temperature of 36.5°C (97.7°F). He weighs 84 kg (185.1 lb) and is 175 cm (5 ft 7 in) tall. Physical exam, he has suprapubic tenderness. A bladder scan reveals 700 ml of urine. A Foley catheter is inserted and the urine is drained. Initial laboratory tests and their follow up 8 hours after admission are shown below. Admission 8 hours after admission Serum potassium 4.2 mmol/L Serum potassium 4.0 mmol/L Serum sodium 140 mmol/L Serum sodium 142 mmol/L Serum chloride 102 mmol/L Serum chloride 110 mmol/L Serum creatinine 1.4 mg/dL Serum creatinine 1.6 mg/dL Serum blood urea nitrogen 64 mg/dL Serum blood urea nitrogen 62 mg/dL Urine output 250 mL Urine output 260 mL A senior attending suggests a consultation with Nephrology. Which of the following best justifies this suggestion?

Estimated glomerular filtration rate (eGFR)

Serum blood urea nitrogen (BUN)

Assessment of vitamin/mineral status for USMLE Step 2 CK: High-Yield Biochemistry Lessons

Fat-Soluble Vitamins - Gauging the Grease

Vitamin A (Retinol):
- Serum retinol is the primary measure, but levels only drop after liver stores are significantly depleted (late indicator).
- Relative Dose Response (RDR) test can detect subclinical deficiency.
Vitamin D (Calciferol):
- Best test: Serum $25(OH)D$ (calcidiol) reflects total body stores from diet and sun.
- Deficiency: <20 ng/mL; Insufficiency: 21-29 ng/mL.
Vitamin E (Tocopherol):
- Plasma α-tocopherol concentration.
- For accuracy, assess the ratio of α-tocopherol to total plasma lipids, especially in hyperlipidemia.
Vitamin K (Phylloquinone/Menaquinones):
- Functional measure: Prothrombin Time (PT) / INR is prolonged.
- Specific marker: PIVKA-II (Protein Induced by Vitamin K Absence).

⭐ Serum $1,25(OH)_2D$ (calcitriol) is a poor indicator of Vitamin D status; it's often normal or even elevated in early deficiency due to secondary hyperparathyroidism.

Water-Soluble Vitamins - The B12 & Folate Feud

Shared Feature: Both B12 and Folate deficiency cause megaloblastic anemia due to impaired DNA synthesis in hematopoietic cells. This leads to hypersegmented neutrophils and macro-ovalocytes.
The Trap: Administering folate to a B12-deficient patient can correct the anemia, but it does not halt the progression of irreversible neurological damage. This "masking" effect is a critical clinical point.

Folate and B12 Metabolism with Homocysteine Link

Feature	Vitamin B12 (Cobalamin)	Folate (B9)
Neurologic Sx	YES (Subacute Combined Degeneration)	NO
↑ Homocysteine	Yes	Yes
↑ Methylmalonic Acid (MMA)	Yes	No
Common Causes	Pernicious anemia, gastrectomy, veganism	Alcoholism, pregnancy, poor diet

📌 Mnemonic: Remember B12 is needed for 2 reactions (Methionine synthase & Methylmalonyl-CoA mutase), while Folate is needed for 1 (Methionine synthase).

Essential Minerals - Ironing Out the Details

Iron (Fe): Key for heme synthesis & O₂ transport.
- Assessment: ↓ Ferritin (first to drop), ↑ TIBC, ↓ Serum Fe, ↑ RDW.
- Deficiency: Microcytic anemia, koilonychia (spoon nails), pica.
- Overload: ↑ Ferritin, ↑ Serum Fe, ↓ TIBC.
Zinc (Zn): Cofactor for numerous enzymes.
- Deficiency: Acrodermatitis enteropathica, alopecia, dysgeusia, impaired wound healing.
Copper (Cu): Component of ceruloplasmin, cytochrome c oxidase.
- Deficiency (Menkes disease): Brittle, "kinky" hair; growth failure.
Iodine (I): Required for thyroid hormone (T3/T4) synthesis.
- Deficiency: Goiter, hypothyroidism, cretinism.

⭐ In iron deficiency, ferritin is the first lab to decrease. TIBC increases as the liver produces more transferrin to maximize iron binding.

Koilonychia (Spoon Nails) in Iron Deficiency Anemia

Vitamin D status is best assessed by measuring serum 25-hydroxyvitamin D, not 1,25-dihydroxyvitamin D.

For B12 deficiency, elevated methylmalonic acid (MMA) and homocysteine are more sensitive than serum B12 levels alone.

RBC folate is a better indicator of long-term folate status than serum folate.

Ferritin is the most sensitive and specific test for diagnosing iron deficiency anemia.

Assess thiamine (B1) deficiency with erythrocyte transketolase activity before and after TPP administration.

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