Bone and blood calcium

The sensory receptor detects the change, the control center compares it with the set point, and the effector carries out the response that reverses the change.

• It detects the change in the regulated variable:
• It compares the variable with the set point:
• Correct: It produces the response that moves the variable back toward the set point:

At threshold, voltage-gated sodium channels open, sodium rushes in, and the membrane depolarizes rapidly.

• Correct: Voltage-gated sodium channels:
• Potassium leak channels:
• Ligand-gated chloride channels:

Osteoclasts dissolve bone mineral with acid and digest collagen with enzymes, releasing calcium and phosphate into the blood.

• Osteoblast:
• Correct: Osteoclast:
• Osteocyte:

Tingling and a hand spasm with the cuff are signs of overexcitable nerves and muscles, the hallmark of hypocalcemia. A calcium of 6.8 mg/dL is well below the normal 8.5 to 10.5 mg/dL.

• Correct: 6.8 mg/dL: Correct. Low calcium makes nerves and muscles overexcitable.
• 9.6 mg/dL: 9.6 mg/dL is in the middle of the normal range and would not cause tetany.
• 10.4 mg/dL: 10.4 mg/dL is at the top of normal; it would not make nerves overexcitable.
• 13.5 mg/dL: 13.5 mg/dL is hypercalcemia, which makes nerves and muscles less excitable: weakness, not spasm.

Calcium ions on the outside of the membrane make voltage-gated sodium channels harder to open. With fewer of them, the channels open with little or no stimulus, so nerves and muscles fire spontaneously: tingling, cramps and tetany. Contraction itself still has enough calcium, mostly from stores inside muscle cells.

• Muscle cells store more calcium inside when blood calcium is low: Muscle cells do not respond to low blood calcium by storing more inside. The effect is on the membrane's sodium channels.
• Low calcium lowers the resting membrane potential to zero: Low calcium does not wipe out the resting potential. It changes how easily the sodium channels open.
• Correct: Fewer calcium ions outside let voltage-gated sodium channels open more easily: Correct. Less calcium outside, less brake on the sodium channels, more firing.
• Low calcium blocks the release of neurotransmitter: Very low calcium can reduce neurotransmitter release, which would weaken signals. The dominant effect, overexcitability, comes from the sodium channels.

Low calcium triggers the calcium-raising hormone, which acts on all three effectors: bone releases calcium, the kidneys keep calcium and lose phosphate, and the kidneys activate vitamin D so the intestine absorbs more. Calcium rises, and hormone release falls again: negative feedback.

• Release of the calcium-raising hormone from the small glands behind the thyroid: up. Fewer calcium ions bind the receptor protein on the gland cells, so they release more hormone within seconds.
• Osteoclast activity: up. The hormone acts on osteoblasts, which signal more osteoclasts to form and work harder, releasing calcium from bone.
• Calcium lost in the urine: down. The hormone makes the kidney tubules return more calcium from the forming urine to the blood.
• Phosphate lost in the urine: up. The hormone makes the kidneys keep less phosphate, so more is excreted and it does not bind the freed calcium.
• Activation of vitamin D in the kidneys: up. The hormone switches on the kidney step that finishes activating vitamin D.
• Calcium absorbed from food by the intestine: up. More activated vitamin D makes the intestinal lining absorb more calcium, over a day or more.

Vitamin D deficiency cuts calcium absorption. The loop defends blood calcium by raising the calcium-raising hormone, which takes calcium from bone and dumps phosphate in the urine. Blood calcium may stay near normal, but bone pays: resorption rises and new matrix cannot mineralize, which in children causes rickets.

• Fraction of dietary calcium absorbed by the intestine: down. Without vitamin D to activate, the intestinal lining makes too few calcium transport proteins, so it absorbs only a small fraction of the calcium eaten.
• Release of the calcium-raising hormone: up. Less calcium enters the blood, calcium dips, and the gland cells release more hormone to hold it up.
• Osteoclast activity: up. More calcium-raising hormone acts through osteoblasts to drive osteoclasts, withdrawing calcium from bone.
• Phosphate lost in the urine: up. The raised hormone makes the kidneys keep less phosphate.
• Mineralization of newly laid osteoid: down. Too little calcium and phosphate reach new osteoid, so it stays soft and unmineralized.

Absorbed: 25% of 800 = 200 mg. Net from the gut: 200 − 100 = 100 mg. Out in urine: 150 mg. Output exceeds net input by 150 − 100 = 50 mg a day, and bone supplies that difference to keep the blood level steady.

• 0 mg: She would be in balance only if net absorption equaled urine loss; here it is 100 mg against 150 mg.
• Correct: 50 mg: Correct. 150 mg lost in urine minus 100 mg net absorbed leaves a 50 mg daily shortfall that bone covers.
• 100 mg: 100 mg is her net absorption from the gut, not the shortfall.
• 200 mg: 200 mg is the amount absorbed before the 100 mg released back into the gut is subtracted.

The loop protects blood calcium first. When intake falls short, the calcium-raising hormone increases bone resorption and kidney calcium saving, so the blood level stays normal. By mass balance, the shortfall comes out of the skeleton, which slowly thins.

• Her diet has been adequate for her needs after all: A normal blood level says the loop is working, not that intake is enough. The shortfall is being covered by bone.
• Correct: Her bones have been covering the shortfall: Correct. Normal blood calcium, thinning bone.
• Her kidneys have been making calcium: The kidneys can keep calcium from being lost, but no organ can make calcium; it can only be absorbed from food.
• Her blood calcium test must be wrong: A normal result is exactly what the loop is expected to produce, even with a poor intake.

With no thyroid, she has none of its calcium-lowering hormone, yet her calcium is normal. The calcium-raising hormone from the small glands, with activated vitamin D, does the everyday regulation; when calcium rises, its release simply falls. Many exams still present the thyroid's calcium-lowering hormone as an equal partner, but its adult role is minor.

• It is the main regulator of blood calcium in adults: If it were the main regulator, losing it would disturb her calcium. It did not.
• It has been replaced by the tablets: Her tablets replace the thyroid's other hormones, which set how fast cells use fuel, not the calcium-lowering hormone.
• Correct: It plays only a minor role in adult calcium control: Correct. Normal calcium without it shows its adult role is small.
• It is made by the small glands instead: The small glands make the calcium-raising hormone, not the thyroid's calcium-lowering one.