A 28-year-old African American woman presents to her primary care physician with two weeks of nausea, abdominal pain, and increased urination. She states she has had kidney stones in the past and is concerned because her current pain is different in character from what she had experienced then. In addition she reports increasing weakness and fatigue over the past several months as well as mild shortness of breath. Chest radiography shows bilateral hilar adenopathy. Which of the following processes is most likely responsible for her current symptoms?

Increased intestinal absorption of calcium

Osteoclast-driven bone resorption

Ectopic parathyroid hormone release

Increased production of parathyroid hormone

Increased renal calcium reabsorption

A 69-year-old woman is brought to the emergency department because of fatigue and lethargy for 5 days. She has also had weakness and nausea for the last 3 days. She has sarcoidosis, major depressive disorder, and hypertension. She had a stroke 5 years ago. Current medications include aspirin, nifedipine, prednisolone, fluoxetine, and rosuvastatin, but she has not taken any of her medications for 7 days due to international travel. Her temperature is 36.1°C (96.9°F), pulse is 95/min, and blood pressure is 85/65 mm Hg. She is lethargic but oriented. Examination shows no other abnormalities. Her hemoglobin concentration is 13.4 g/dL and leukocyte count is 9,600/mm3. Both serum cortisol and ACTH levels are decreased. This patient is most likely to have which of the following additional laboratory abnormalities?

Normal anion gap metabolic acidosis

A 70-year-old man is brought to the emergency department by his wife because of lethargy, confusion, and nausea for the past 2 days. He has previously been healthy and has no past medical history. His only medications are a daily multivitamin and acetaminophen, which he takes daily for hip pain. Vital signs are within normal limits. He is disoriented to place and time but recognizes his wife. The remainder of his physical examination shows no abnormalities. Laboratory studies show a hemoglobin concentration of 9.1 g/dL, a serum calcium concentration of 14.7 mg/dL, and a serum creatinine of 2.2 mg/dL (previously 0.9 mg/dL). Which of the following is the most likely underlying mechanism of this patient's condition?

Overproliferation of plasma cells

Increased serum levels of 1,25-hydroxyvitamin D

Excessive consumption of calcium

Excess PTH secretion from parathyroid glands

An 8-year-old boy is brought to the pediatrician by his mother with nausea, vomiting, and decreased frequency of urination. He has acute lymphoblastic leukemia for which he received the 1st dose of chemotherapy 5 days ago. His leukocyte count was 60,000/mm3 before starting chemotherapy. The vital signs include: pulse 110/min, temperature 37.0°C (98.6°F), and blood pressure 100/70 mm Hg. The physical examination shows bilateral pedal edema. Which of the following serum studies and urinalysis findings will be helpful in confirming the diagnosis of this condition?

Hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and urate crystals in the urine

Hyperuricemia, hyperkalemia, hyperphosphatemia, and urinary monoclonal spike

Hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, urine supernatant pink, and positive for heme

Hyperkalemia, hyperphosphatemia, hypocalcemia, and extremely elevated creatine kinase (MM)

Hyperuricemia, hyperkalemia, hyperphosphatemia, lactic acidosis, and oxalate crystals

A 52-year-old man comes to the physician because of a 4-month history of fatigue, weakness, constipation, decreased appetite, and intermittent flank pain. He takes ibuprofen for knee and shoulder pain. Physical examination shows mild tenderness bilaterally in the costovertebral areas. His serum calcium concentration is 11.2 mg/dL, phosphorus concentration is 2.5 mg/dL, and N-terminal parathyroid hormone concentration is 830 pg/mL. Which of the following steps in vitamin D metabolism is most likely increased in this patient?

25-hydroxycholecalciferol → 1,25-dihydroxycholecalciferol

Ergocalciferol → 25-hydroxyergocalciferol

7-dehydrocholesterol → cholecalciferol

25-hydroxycholecalciferol → 24,25-dihydroxycholecalciferol

Cholecalciferol → 25-hydroxycholecalciferol

Macrominerals (Na, K, Ca, Mg, P, Cl) for USMLE Step 2 CK: High-Yield Biochemistry Lessons

Sodium & Potassium - Salty Nerve Vibes

Maintains electrochemical gradients essential for nerve conduction and muscle contraction.

Feature	Sodium (Na+)	Potassium (K+)
Function	Main ECF cation; nerve depolarization	Main ICF cation; nerve repolarization, muscle function
Deficiency (Hypo-)	CNS dysfunction (confusion, coma)	Muscle weakness, cramps, U waves on EKG
Excess (Hyper-)	CNS irritability, thirst, lethargy	Muscle weakness, paralysis, peaked T waves on EKG

⭐ Correcting chronic hyponatremia too quickly (>8-12 mEq/L in 24h) can cause osmotic demyelination syndrome. From low to high, your pons will die.

📌 Hyperkalemia Treatment (C BIG K Drop):

Calcium gluconate
Bicarbonate / Beta-agonists
Insulin + Glucose
Kayexalate
Diuretics / Dialysis

Calcium & Phosphate - Bone & Stone Story

Inverse Relationship: Serum Ca & P levels are reciprocally regulated. Their product is crucial for bone mineralization into hydroxyapatite, $Ca_{10}(PO_4)_6(OH)_2$.
Hormonal Regulators:
- PTH: ↑ Serum Ca, ↓ Serum P. 📌 "Phosphate Trashing Hormone."
- Vitamin D (1,25-OH₂): ↑ Serum Ca, ↑ Serum P by increasing gut absorption.
- Calcitonin: ↓ Serum Ca; opposes PTH action.
Clinical Signs:
- Hypocalcemia: Neuromuscular excitability (tetany, Chvostek/Trousseau signs).
- Hypercalcemia: 📌 "Bones, stones, groans, thrones, psychiatric overtones."

PTH-Vitamin D-FGF23 axis: Calcium & Phosphate Regulation

⭐ In primary hyperparathyroidism, expect ↑ PTH, ↑ Serum Ca, ↓ Serum P, and ↑ urinary cAMP. Malignancy-related hypercalcemia (e.g., PTHrP) will show ↓ PTH.

Magnesium & Chloride - Cofactor & Charge Crew

Magnesium (Mg²⁺)

Function: Essential cofactor for ATP-dependent reactions (e.g., kinases). Required for PTH secretion and action. Stabilizes membranes and DNA.
Hypomagnesemia: Causes neuromuscular excitability (tetany, tremors), cardiac arrhythmias (Torsades de Pointes), and ↓PTH secretion.
- Commonly caused by diuretics, alcohol abuse, diarrhea, PPIs.

⭐ Refractory Hypokalemia & Hypocalcemia: Low Mg²⁺ impairs renal K⁺ reabsorption and causes PTH resistance. Always check and replete magnesium if potassium or calcium are difficult to correct.

Chloride (Cl⁻)

Function: Primary extracellular anion, balancing the positive charge of Na⁺. Crucial for maintaining osmotic pressure and producing gastric acid (HCl).
Hypochloremia: Often seen with metabolic alkalosis due to vomiting (loss of HCl) or diuretic use.

Sodium imbalance impacts neurologic function; rapid correction of hyponatremia risks osmotic demyelination.

Potassium levels dictate cardiac stability, with classic ECG changes (U waves vs. peaked T waves).

Hypocalcemia causes tetany (Chvostek/Trousseau signs), while hypercalcemia presents with "stones, bones, groans."

Hypomagnesemia can trigger torsades de pointes and worsen hypokalemia and hypocalcemia.

Severe hypophosphatemia is a key feature of refeeding syndrome.

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