2. OVERVIEW OF CALCIUM AND REGULATION IN THE
EXTRACELLULAR FLUID AND PLASMA
Extracellular fluid calcium concentration is normally regulated precisely; it
seldom rises or falls more than a few percent from the normal value of
about 9.4 mg/dl, which is equivalent to 2.4 millimoles of calcium per liter.
This precise control is essential because calcium plays a key role in many
physiological processes, including contraction of skeletal, cardiac, and
smooth muscles, blood clotting, and transmission of nerve
impulses.
Excitable cells such as neurons are sensitive to changes in calcium ion
concentrations, and increases in calcium ion concentration above normal
(hypercalcemia) cause progressive depression of the nervous system;
conversely, decreases in calcium concentration (hypocalcemia) cause
the nervous system to become more excited.
3. An important feature of extracellular calcium regulation is that only about
0.1 percent of the total body calcium is in the extracellular fluid, about 1
percent is in the cells and its organelles, and the rest is stored in
bones.
Therefore, the bones can serve as large reservoirs, releasing calcium
when extracellular fluid concentration decreases and storing excess
calcium.
4. CALCIUM IN THE PLASMA AND INTERSTITIAL FLUID
The calcium in the plasma is present in three forms:
(1) About 41 percent (1 mmol/L) of the calcium is combined with the
plasma proteins and in this form is nondiffusible through the capillary
membrane
(2) about 9 percent of the calcium (0.2 mmol/L) is diffusible through the
capillary membrane but is combined with anionic substances of the
plasma and interstitial fluids (citrate and phosphate, for instance) in such a
manner that it is not ionized
(3) the remaining 50 percent of the calcium in the plasma is both diffusible
through the capillary membrane and ionized.
5.
6. Hypocalcemia Causes Nervous System Excitement and Tetany.
When the extracellular fluid concentration of calcium ions falls below
normal, the nervous system becomes progressively more excitable
because this phenomenon causes increased neuronal membrane
permeability to sodium ions, allowing easy initiation of action potentials.
hypocalcemia causes tetany.
8. Tetany ordinarily occurs when the blood concentration of calcium falls
from its normal level of 9.4 mg/dl to about 6 mg/dl, which is only 35
percent below the normal calcium concentration, and it is usually
lethal at about 4 mg/dl.
9. Hypercalcemia Depresses Nervous System and Muscle Activity.
• the nervous system becomes depressed
• reflex activities of the central nervous system are sluggish
• increased calcium ion concentration decreases the QT interval of the
heart
• lack of appetite
• constipation
• depressed contractility of the muscle walls of the gastrointestinal tract.
10. ABSORPTION AND EXCRETION OF CALCIUM AND PHOSPHATE
Intestinal Absorption and Fecal Excretion of Calcium and
Phosphate.
The usual rates of intake are about 1000 mg/day each for calcium about
the amounts in 1 liter of milk.
Normally, divalent cations such as calcium ions are poorly absorbed
from the intestines.
vitamin D promotes calcium absorption by the intestines, and about 35
percent (350 mg/day) of the ingested calcium is usually absorbed; the
remaining calcium in the intestine is excreted in the feces
11. An additional 250 mg/day of calcium enters the intestines via secreted
gastrointestinal juices and sloughed mucosal cells.
Thus, about 90 percent (900 mg/ day) of the daily intake of calcium is
excreted in the feces
12.
13. Renal Excretion of Calcium.
Approximately 10 percent (100 mg/day) of the ingested calcium is
excreted in the urine.
About 41 percent of the plasma calcium is bound to plasma proteins
and is therefore not filtered by the glomerular capillaries.
The remainder is combined with anions such as phosphate (9 percent)
or ionized (50 percent) and filtered through the glomeruli
into the renal tubules.
Normally, the renal tubules reabsorb 99 percent of the filtered calcium,
and about 100 mg/day are excreted in the urine.
14. VITAMIN D
Vitamin D has a potent effect to increase calcium absorption from the
intestinal tract
it also has important effects on bone deposition and bone
reabsorption
However, vitamin D itself is not the active substance that actually
causes these effects.
Instead, vitamin D must first be converted through a succession of
reactions in the liver and the kidneys to the final active product,
1,25-dihydroxycholecalciferol, also called 1,25(OH)2D3.
15. Cholecalciferol (Vitamin D3) Is Formed in the Skin.
Vitamin D3 (also called cholecalciferol) is the most important of these
compounds and is formed in the skin as a result of irradiation of 7-
dehydrocholesterol, a substance normally in the skin, by ultraviolet
rays from the sun.
16.
17. Cholecalciferol Is Converted to 25-Hydroxycholecalciferol in the
Liver.
The first step in the activation of cholecalciferol is to convert it to 25-
hydroxycholecalciferol, which occurs in the liver.
18.
19. Formation of 1,25-Dihydroxycholecalciferol in the Kidneys and Its
Control by Parathyroid Hormone.
the conversion in the proximal tubules of the kidneys of 25-
hydroxycholecalciferol to 1,25-dihydroxycholecalciferol.
This latter substance is by far the most active form of vitamin D
the conversion of 25- hydroxycholecalciferol to 1,25-
dihydroxycholecalciferol requires PTH.
In the absence of PTH, almost none of the 1,25 dihydroxycholecalciferol
is formed.
20.
21. ACTIONS OF VITAMIN D
Vitamin D receptors are present in most cells in the body and are
located mainly in the nuclei of target cells.
Similar to receptors for steroids and thyroid hormone, the vitamin D
receptor has hormone-binding and DNA-binding domains. The vitamin D
receptor forms a complex with another intracellular receptor, the
retinoid-X receptor, and this complex binds to DNA and activates
transcription in most instances
22. “Hormonal” Effect of Vitamin D to Promote Intestinal Calcium
Absorption.
formation of calbindin, a calcium-binding protein, in the intestinal
epithelial cells.
This protein functions in the brush border of these cells to transport
calcium into the cell cytoplasm
23. Vitamin D Promotes Phosphate Absorption by the Intestines.
Vitamin D Decreases Renal Calcium and Phosphate Excretion.
