A 65-year-old female with chronic renal failure presents with recent onset of bone pain. Serum analysis reveals decreased levels of calcium and elevated levels of parathyroid hormone. One of the mechanisms driving the elevated PTH is most similar to that seen in:

Decreased functioning of the calcium-sensing receptor (CASR)

A 55-year-old man with long-standing diabetes presents with a fragility fracture. He has chronic renal failure secondary to his diabetes. His serum parathyroid hormone concentration is elevated. You measure his serum concentration of 25(OH)-vitamin D and find it to be normal, but his concentration of 1,25(OH)-vitamin D is decreased. Which of the following represents a correct pairing of his clinical condition and serum calcium level?

Secondary hyperparathyroidism with low serum calcium

Secondary hyperparathyroidism with elevated serum calcium

Primary hyperparathyroidism with low serum calcium

Tertiary hyperparathyroidism with low serum calcium

Primary hyperparathyroidism with elevated serum calcium

A 76-year-old woman presents to the office with a generalized weakness for the past month. She has a past medical history significant for uncontrolled hypertension and type 2 diabetes mellitus. Her temperature is 37.0°C (98.6°F), blood pressure is 135/82 mm Hg, pulse is 90/min, respiratory rate is 17/min, and oxygen saturation is 99% on room air. Physical exam shows no remarkable findings. Her last recorded glomerular filtration rate was 30 mL/min. A radiograph of the patient’s hand is given. Which of the following lab findings is most likely to be found in this patient?

Increased PTH, decreased calcium, increased phosphate

Increased PTH, decreased calcium, decreased phosphate

Normal PTH, increased calcium, normal phosphate

Increased PTH, increased calcium, decreased phosphate

Increased PTH, increased calcium, increased phosphate

A 55-year-old woman presents to the emergency room with severe abdominal pain for the past 24 hours. She has also noticed blood in her urine. She does not have any significant past medical history. Family history is significant for her mother having cholecystitis status post cholecystectomy at age 45. Her vital signs include: temperature 36.8°C (98.2°F), pulse 103/min, respiratory rate 15/min, blood pressure 105/85 mm Hg. Physical examination is significant for a woman continuously moving on the exam table in an attempt to get comfortable. Laboratory findings are significant for the following: Serum electrolytes Na 138 mEq/L N: 135–145 mEq/L K 4.0 mEq/L N: 3.5–5.0 mEq/L Cl 102 mEq/L N: 98–108 mEq/L CO2 27 mEq/L N: 22–32 mEq/L Ca 9.2 mEq/dL N: 8.4–10.2 mEq/dL PO4 3.5 mg/dL N: 3.0–4.5 mg/dL A 24-hour urine collection is performed and reveals a urinary calcium of 345 mg/day (ref: < 300 mg/day in men; < 250 mg/day in women). A non-contrast CT of the abdomen is performed and is shown in the exhibit. The patient’s symptoms pass within the next 12 hours with hydration and acetaminophen for pain management. She is prescribed a medication to prevent subsequent episodes. At which of the following parts of the nephron does this medication most likely work?

Descending limb of the loop of Henle

Thick ascending limb of the loop of Henle

In a healthy patient with no renal abnormalities, several mechanisms are responsible for moving various filtered substances into and out of the tubules. Para-aminohippurate (PAH) is frequently used to estimate renal blood flow when maintained at low plasma concentrations. The following table illustrates the effect of changing plasma PAH concentrations on PAH excretion: Plasma PAH concentration (mg/dL) | Urinary PAH concentration (mg/dL) 0 | 0 10 | 60 20 | 120 30 | 150 40 | 180 Which of the following mechanisms best explains the decreased rate of increase in PAH excretion observed when plasma PAH concentration exceeds 20 mg/dL?

Saturation of PAH transport carriers

Decreased glomerular filtration of PAH

Increased rate of PAH reabsorption

Increased flow rate of tubular contents

Increased diffusion rate of PAH

An investigator is studying membranous transport proteins in striated muscle fibers of an experimental animal. An electrode is inserted into the gluteus maximus muscle and a low voltage current is applied. In response to this, calcium is released from the sarcoplasmic reticulum of the muscle fibers and binds to troponin C, which results in a conformational change of tropomyosin and unblocking of the myosin-binding site. The membranous transport mechanism underlying the release of calcium into the cytosol most resembles which of the following processes?

Uptake of fructose by small intestinal enterocytes

Opening of acetylcholine receptors at neuromuscular junction

Reabsorption of glucose by renal tubular cells

Secretion of doxorubicin from dysplastic colonic cells

Removal of calcium from cardiac myocytes

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

Calcium and phosphate handling for USMLE Step 3: High-Yield Physiology Lessons

Overview - The Filtration Fraction

Calcium (Ca²⁺): Only the unbound, ionized fraction is filtered by the glomerulus.
- ~60% of plasma Ca²⁺ is filterable (ionized and complexed).
- ~40% is bound to albumin and other proteins; not filtered.
Phosphate (PO₄³⁻): Most plasma phosphate is filterable.
- ~85-90% is freely filtered (ionized or complexed with Na⁺, Ca²⁺, Mg²⁺).
- ~10-15% is protein-bound; not filtered.

⭐ Acidosis ↓ albumin binding → ↑ ionized Ca²⁺.

Proximal Tubule - The Bulk Reabsorber

Calcium ($Ca^{2+}$) Reabsorption (~65-70%):
- Paracellular (~80%): The primary route, driven by the lumen-positive electrochemical gradient and solvent drag.
- Transcellular (~20%): A minor, active component.
Phosphate ($PO_4^{3-}$) Reabsorption (~85%):
- Mediated by apical Na⁺/PO₄³⁻ cotransporters (NPT2a, NPT2c).
- PTH Regulation: PTH inhibits NPT2a/c activity, promoting their removal from the apical membrane. This action decreases phosphate reabsorption, leading to phosphaturia.

Renal tubule calcium and phosphate handling overview

⭐ In humoral hypercalcemia of malignancy, PTH-related peptide (PTHrP) also inhibits NPT2a/c, causing significant renal phosphate wasting and hypophosphatemia.

TAL & DCT - Hormonal Fine‑Tuning

Thick Ascending Limb (TAL):
- Reabsorbs ~25% of filtered $Ca^{2+}$.
- Mechanism: Passive, paracellular, driven by the lumen-positive potential generated by the NKCC2 transporter.
- PTH indirectly enhances reabsorption here.
Distal Convoluted Tubule (DCT):
- Reabsorbs ~8% of filtered $Ca^{2+}$.
- Mechanism: Active, transcellular; the key site for fine-tuning.
- PTH Action:
  - Binds to basolateral receptors.
  - Upregulates and opens apical TRPV5 $Ca^{2+}$ channels.
  - $Ca^{2+}$ binds to calbindin for transport to the basolateral membrane.
  - Extruded into blood via Na⁺/$Ca^{2+}$ exchanger (NCX) and $Ca^{2+}$-ATPase (PMCA).

Calcium reabsorption in the distal convoluted tubule

⭐ Thiazide diuretics block the Na⁺-Cl⁻ cotransporter (NCC) in the DCT. This reduces intracellular $Na^{+}$, which enhances the activity of the basolateral Na⁺/$Ca^{2+}$ exchanger, leading to increased $Ca^{2+}$ reabsorption and potential hypercalcemia.

Key Regulators - The Hormone Squad

Hormone	Effect on Serum Ca²⁺	Effect on Serum PO₄³⁻	Renal Action (Ca²⁺ & PO₄³⁻)
PTH	↑	↓	↑ Ca²⁺ reabsorption (DCT) ↓ PO₄³⁻ reabsorption (PCT) 📌 Phosphate Trashing Hormone
Calcitriol	↑	↑	↑ Ca²⁺ & ↑ PO₄³⁻ reabsorption
FGF23	↔	↓	↓ PO₄³⁻ reabsorption ↓ Calcitriol synthesis
%%{init: {'flowchart': {'htmlLabels': true}}}%%
flowchart TD

LowCa["<b>🩸 Low Serum Ca2+</b><br><span style='display:block; text-align:left; color:#555'>• Hypocalcemia state</span><span style='display:block; text-align:left; color:#555'>• Initial stimulus</span>"]
HighPTH["<b>⬆️ PTH Level</b><br><span style='display:block; text-align:left; color:#555'>• Parathyroid gland</span><span style='display:block; text-align:left; color:#555'>• Hormonal response</span>"]

subgraph Kidney["<b>🧬 Kidney Response</b>"]
    CaRe["<b>⬆️ Ca2+ Reabsorp</b><br><span style='display:block; text-align:left; color:#555'>• Distal tubule</span><span style='display:block; text-align:left; color:#555'>• Conserve Calcium</span>"]
    PORe["<b>⬇️ PO4 3- Reabsorp</b><br><span style='display:block; text-align:left; color:#555'>• Proximal tubule</span><span style='display:block; text-align:left; color:#555'>• High Phosphate loss</span>"]
    Calc["<b>⬆️ Calcitriol</b><br><span style='display:block; text-align:left; color:#555'>• 1-alpha activation</span><span style='display:block; text-align:left; color:#555'>• Vitamin D3 increase</span>"]
end

LowCa --> HighPTH
HighPTH --> Kidney

style LowCa fill:#FFF7ED, stroke:#FFEED5, stroke-width:1.5px, rx:12, ry:12, color:#C2410C
style HighPTH fill:#F7F5FD, stroke:#F0EDFA, stroke-width:1.5px, rx:12, ry:12, color:#6B21A8
style CaRe fill:#EEFAFF, stroke:#DAF3FF, stroke-width:1.5px, rx:12, ry:12, color:#0369A1
style PORe fill:#EEFAFF, stroke:#DAF3FF, stroke-width:1.5px, rx:12, ry:12, color:#0369A1
style Calc fill:#F1FCF5, stroke:#BEF4D8, stroke-width:1.5px, rx:12, ry:12, color:#166534
style Kidney fill:#F6F5F5, stroke:#E7E6E6, stroke-width:1.5px, color:#525252


> ⭐ FGF23 is the primary phosphaturic hormone. In chronic kidney disease (CKD), FGF23 levels rise early to maintain normal phosphate levels, but this contributes to suppressing Vitamin D activation.

##  High‑Yield Points - ⚡ Biggest Takeaways

> *   **Parathyroid hormone (PTH)** **increases serum Ca²⁺** while **decreasing serum PO₄³⁻**.
> *   PTH **inhibits Na/PO₄ cotransport** in the **proximal tubule** and **stimulates Ca²⁺ reabsorption** in the **distal tubule**.
> *   **Active Vitamin D (Calcitriol)** **increases absorption of both Ca²⁺ and PO₄³⁻** from the gut and kidney.
> *   **FGF23** acts to **decrease serum phosphate** by promoting its excretion in the urine.
> *   The **distal convoluted tubule (DCT)** is the primary site for **hormonally-regulated Ca²⁺ fine-tuning**.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play