General Physiology

Calcium Homeostasis

Assignment number: 01
Submitted by: Eiman Meer
Submitted to: Dr. Khadim Shah
Date of submission: March 25, 2020

COMSATS University Islamabad-Abbottabad Campus

Assignment 1 Page 1
Calcium metabolism
Calcium metabolism is movement and regulation of calcium ions (Ca2+) in (by gut) and out (by
gut and kidneys) of body, and between body compartments:

 blood plasma (1.4 mmol/L ionizedtotal 2.2–2.6 mmol/L in plasma 9 mmol in blood)
 extracellular fluids (22 mmol)
 intracellular fluids (<0.0002 mmol/L)
 bone (almost 1 kg,99% in skeleton in form of calcium phosphate)

The concentration of calcium ions in intracellular fluid is more than 7,000 times lower than in
blood plasma (i.e. at <0.0002 mmol/L, compared with 1.4 mmol/L in plasma)

Normal plasma levels

The plasma total calcium concentration is in range of 2.2–2.6 mmol/L (9–10.5 mg/dL), and the
normal ionized calcium is 1.3–1.5 mmol/L (4.5–5.6 mg/dL). The amount of total calcium in
blood varies with level of plasma albumin, main carrier of protein-bound calcium in blood.
Between 35 and 50% of calcium in plasma is protein-bound. 5–10% is in form of complexes
with organic acids and phosphates. The remainder (50–60%) is ionized.

Functions
Ca play an important role to maintain some important body functions such as

Ca controls nerve excitability. The effect is mainly on peripheral neuromuscular

mechanism. Fibrillary twitching can be produced by fusing of muscle with Ca free fluid.
Automatic ganglia also become hyper irritable.
It is necessary for the maintenance of integrity of skeletal muscles. An increase in ionized
Ca results in an increase in contractility and vice versa.
It is very essential for maintaining tone and contractility of heart. Ca is antidotal to
depressant action of K.
Ca take part in formation of certain tissue and bones.

Sources
Not all calcium in diet can be readily absorbed from gut. The calcium is most readily absorbed is
found in dairy products (72%), vegetables (7%), grains (5%), legumes (4%), fruit (3%),
protein (3%). The calcium contained in vegetable matter is often complexed with phytates,
oxalates, citrate and other organic acids, such as long-chained fatty acids (e.g. palmitic acid).

Bone storage
Calcium flow to and from bone may be positive, negative, or neutral. When it is neutral, about
5–10 mmol is turned over day. Bone serves as important storage point for calcium, as it contains
99% of total body calcium.

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Intestinal absorption
The normal adult diet contains about 25 mmol of calcium per day. Only about 5 mmol of
this is absorbed into the body per day.
Calcium is absorbed across intestinal epithelial cell's brush border membrane. The
TRPV6 channel is major player in intestinal Ca2+ uptake.
After cellular uptake, calcium is immediately bound to Calbindin, vitamin D-dependent
calcium-binding protein.
Calbindin transfers calcium directly into epithelial cell's endoplasmic reticulum,
through which calcium is transferred to basal membrane on opposite side of cell, without
entering its cytosol or intracellular fluid.
From there calcium pumps (PMCA1) actively transport calcium into body.

Cholesterol (ultraviolet)  Previtamin D3 (isomerization)  Vitamin D3 (Liver)

Calcifediol PTH + Kidneys  Calcitriol (acts on epithelial cells (enterocytes) lining the
small intestine to increase rate of absorption of calcium from intestine)

Reabsorption
Intestine

Since about 15 mmol of calcium is excreted into intestine via bile per day, total amount of
calcium that reaches duodenum and jejunum each day is about 40 mmol (25 mmol from diet plus
15 mmol from bile), of which, 20 mmol is absorbed back into blood. The net result is that about
5 mmol more calcium is absorbed from gut than is excreted into it via bile.

Kidneys

The kidneys filter 250 mmol of calcium ions day in pro-urine (or glomerular filtrate), and resorbs
245 mmol, leading to net average loss in urine of about 5 mmol/d. The quantity of calcium ions
excreted in urine per day is partially under influence of PTH level - high levels of PTH
decreasing rate of calcium ion excretion, and low levels increasing it.

Absorption of phosphate ions

Parathyroid hormone effect quantity of phosphate ions HPO 4-2 excreted in urine. Phosphates
form insoluble salts in combination with calcium ions. High concentrations of HPO4-2 in plasma,
therefore, lower ionized calcium level in extra-cellular fluids. Thus, excretion of more
phosphate than calcium ions in urine raises plasma ionized calcium level, even though total
calcium concentration might be lowered.

Maintaining levels of Calcitriol

The kidney influences plasma ionized calcium concentration by processing vitamin D3 into
calcitriol, active form that is most effective in promoting intestinal absorption of calcium. This

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conversion of vitamin D3 into calcitriol, is also promoted by high plasma parathyroid hormone
levels.

Excretion
Most excretion of excess calcium is via bile and feces, because plasma calcitriol levels (which
ultimately depend on plasma calcium levels) regulate how much of biliary calcium is reabsorbed
from intestinal contents.

Kidneys

Urinary excretion of calcium is normally about 5 mmol (200mg)/day. This is less in comparison
to what is excreted by feces (15 mmol/day).

Regulation of Calcium
Calcium regulation in human body. The plasma ionized calcium concentration is regulated
within narrow limits (1.3–1.5 mmol/L). This is achieved by both parafollicular cells of thyroid
gland, and parathyroid glands constantly sensing (i.e. measuring) concentration of calcium ions
in blood flowing through them.

High plasma level

When concentration rises parafollicular cells of thyroid gland increase their secretion of
Calcitonin, into blood.
Parathyroid glands reduce secretion of parathyroid hormone (PTH).
The resulting high levels of calcitonin in blood stimulate osteoblasts in bone to remove
calcium from the blood plasma, and deposit it as bone.
The reduced levels of PTH inhibit removal of calcium from skeleton. The low levels of PTH
increase loss of calcium in urine, but inhibit loss of phosphate ions via that route. Phosphate
ions will form insoluble salts with calcium ions, thereby removing them from the ionized
calcium pool in blood.
The low levels of PTH also inhibit formation of calcitriol from cholecalciferol (vitamin D3)
by the kidneys.

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 The reduction in blood calcitriol concentration acts (comparatively slowly) on Epithelial
cells (Enterocytes) of duodenum, inhibiting their ability to absorb calcium from intestinal
contents.
The low calcitriol levels also act on bone causing Osteoclasts to release fewer calcium ions
into blood plasma.

Figure 1. Calcium regulation (https://www.google.com/url?sa=i&url=https%3A%2F%2Fmedatrio.com%2Fcalcium-

homeostasis&psig)

Low plasma level

When the plasma ionized calcium level is low or falls the opposite happens.

Calcitonin secretion is inhibited and PTH secretion is stimulated, resulting in calcium

being removed from bone to correct plasma calcium level.
The high plasma PTH levels inhibit calcium loss via urine while stimulating excretion of
phosphate ions via that route.
They also stimulate kidneys to manufacture Calcitriol (a steroid hormone), which
enhances ability of cells lining the gut to absorb calcium from intestinal contents into
blood, by stimulating production of calbindin in these cells.
The PTH stimulated production of calcitriol also causes calcium to be released from bone
into blood, by release of RANKL (a cytokine, or local hormone) from osteoblasts which
increases bone resorptive activity by osteoclasts. These are, however, relatively slow
processes.

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References:
Albright F, Bloomberg E, Drake T and Sulkowitch HW. A comparisonof the effects of
A.T.10 (dihydrotachysterol) and vitamin D on calcium andphosphorusmetabolism in
hypoparathyroidism. J Clin Invest.1938;17: 317-329

Bouillon RA, Auwerx JH, Lissens WD and Pelemans WK. Vitamin Dstatus in the elderly:
seasonal substrate deficiency causesdihydroxycholecalciferol deficiency. Am J Clin
Nutr.1987;45:755-763.

Bronner F. Intestinal calcium absorption: mechanisms and applications. J Nutr.1987;11: 1347-

1352.

P. Pravina, D. Sayaji and M. Avinash. Calcium and its Role in Human Body. International
Journal of Research in Pharmaceutical and Biomedical Sciences .2013: 4:660

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