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Renal system




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USMLE® Step 1 style questions USMLE

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A 67-year-old male comes to his outpatient provider’s office for evaluation of fatigue and diffuse muscle aches. His symptoms started about a year ago and have been progressing over time. He also reports having bowel movement once a week with hard, pellet-like stool formation. Past medical history is significant for insulin-dependent diabetes mellitus type 2 and end-stage renal disease. He underwent a kidney transplant two months ago. His medications include insulin and sirolimus. The patient has a 35-pack-year smoking history but is no longer smoking. In the office, his temperature is 37.6°C (99.7°F), pulse is 68/min, respirations are 14/min and blood pressure is 115/74 mmHg. Laboratory testing reveals the following results:

 Laboratory value  Result 
 Serum chemistry 
 Serum calcium  11.2 mmol/L 
 Serum phosphate  2.4 mmol/L 
 Parathyroid hormone 560 pg/mL 
  *Normal range: 10-55 pg/mL  

Which of the following is the most likely cause of the patient’s presentation? 

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Abdominal pain

hypercalcemia p. 615


hypercalcemia and p. 615

Bladder cancer

hypercalcemia and p. 221

Breast cancer

hypercalcemia and p. 221

Familial hypocalciuric hypercalcemia p. 344

Hypercalcemia p. 615

acute pancreatitis and p. 406

adult T-cell lymphoma p. 437

bisphosphonates for p. 499

calcium carbonate in p. 408

diabetes insipidus p. 351

granulomatous diseases and p. NaN

hyperparathyroidism p. 344

loop diuretics for p. 632

lung cancer p. 709

paraneoplastic syndrome p. 221

PTH-independent p. 350

sarcoidosis and p. 701

succinylcholine p. 571

teriparatide p. 500

thiazides as cause p. 633

Williams syndrome p. 62

Lung cancer p. NaN

hypercalcemia and p. 221


hypercalcemia and p. 221

Ovarian cancer

hypercalcemia and p. 221

PTH-independent hypercalcemia p. 350

Renal cell carcinomas p. 623

hypercalcemia and p. 221

Squamous cell carcinomas

hypercalcemia and p. 221


With hypercalcemia, hyper -means over and -calc- refers to calcium, and -emia refers to the blood, so hypercalcemia means higher than normal calcium levels in the blood, generally over 10.5 mg/dL.

Now, calcium exists as an ion with a double positive charge - Ca2+ - and it’s the most abundant metal in the human body.

So I know what you’re thinking - yeah, we’re all pretty much cyborgs,- Cool, huh?

So about 99% of that calcium is in our bones in the form of calcium phosphate, also called hydroxyapatite.

The last 1% is split so that the majority, about 0.99% is extracellular - which means in the blood and in the interstitial space between cells, and 0.01% is intracellular or inside cells.

High levels of intracellular calcium causes cells to die.

In fact, that’s exactly what happens during apoptosis, also known as programmed cell death.

For that reason, cells end up spending a lot of energy just keeping their intracellular calcium levels low.

Now, calcium gets into the cell through two types of channels, or cell doors, within the cell membrane.

The first type are ligand-gated channels, which are what most cells use to let calcium in, and are primarily controlled by hormones or neurotransmitters.

The second type are voltage-gated channels, which are mostly found in muscle and nerve cells and are primarily controlled by changes in the electrical membrane potential.

So calcium flows in through these channels, and to prevent calcium levels from rising too high, cells kick excess calcium right back out with ATP-dependent calcium pumps as well as Na+-Ca2+ exchangers.

In addition, most of the intracellular calcium is stored within organelles like the mitochondria and smooth endoplasmic reticulum and is released selectively just when it's needed.

Now, the majority of the extracellular calcium is split almost equally between two groups - calcium that is diffusible and calcium that is not diffusible.

Diffusible calcium is separated into two subcategories: free-ionized calcium, which is involved in all sorts of cellular processes like neuronal action potentials, contraction of skeletal, smooth, and cardiac muscle, hormone secretion, and blood coagulation, all of which are tightly regulated by enzymes and hormones.

The other category is complexed calcium, which is where the positively charged calcium is ionically linked to tiny negatively charged molecules like oxalate, which is a small anions that’s normally found in our blood in small amounts.

The complexed calcium forms a molecule that’s electrically neutral and small enough to cross cell membranes, but, unlike free-ionized calcium is not useful for cellular processes.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Calcium block of Na <sup>+</sup> channels and its effect on closing rate" Proceedings of the National Academy of Sciences (1999)
  6. "The diagnosis and management of hypercalcaemia" BMJ (2015)
  7. "Osborn waves in a hypothermic patient" Journal of Community Hospital Internal Medicine Perspectives (2012)

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