Calcium

Calcium and phosphorus are interrelated in terms of their regulation within the human body.
There exists an inverse relationship between calcium and phosphorus: as the levels of one substance increase, the levels of the other typically decrease.
The body works to maintain a specific balance where the ratio of calcium to phosphorus is approximately $2:1$ .

A vast majority, approximately $99\%$ , of the body’s calcium is deposited in the bones and the teeth.
The remaining $1\%$ of calcium is found in the serum (blood), which is utilized to monitor for various disorders and alterations in calcium levels.
Shifts in serum calcium can be caused by changes in:
- Protein levels.
- Vitamin D levels.
- Bone health (since $99\%$ is stored in the skeletal system, bone issues frequently manifest as calcium imbalances).
- Kidney function (the kidneys manage reabsorption in the renal tubules and the activation of vitamin D).
- Parathyroid gland function (regulation through hormone secretion).
- Gastrointestinal (GI) tract function (the site of calcium absorption).

In healthy adults, calcium intake and output are relatively balanced.
In childhood, individuals maintain a positive calcium balance. This entails a net retention of calcium to support skeletal growth and deposition within the developing skeletal system.
In older adults, a negative calcium balance is common. This means calcium output exceeds intake. The efficiency of gastrointestinal calcium absorption decreases with age, contributing to this negative balance.

Dairy products serve as a major source of dietary calcium.
Calcium is relatively insoluble, making it difficult for the body to absorb without the presence of Vitamin D.
Typical daily intake is approximately $1\,g$ per day, though requirements increase during specific life phases, such as childhood.
The composition of the $1\%$ of calcium found in the serum is broken down as follows:
- $50\%$ is in the ionized form ( $Ca^{2+}$ ). This is the physiologically active form, analogous to the active forms of thyroid hormones.
- A large portion is bound to proteins, specifically albumin.
- A small proportion is bound to other substances, including bicarbonate and citrate.

Specific factors are responsible for increasing or decreasing plasma calcium levels.
Factors that increase plasma calcium:
- Parathyroid hormone (PTH).
- Active Vitamin D3, scientifically identified as 125 di hydra dihydroxide called calcium for all.
Factors that decrease plasma calcium:
- Calcitonin: This hormone is produced by the C cells in the thyroid gland. It functions to "tone down" calcium levels and counters the effects of PTH and active Vitamin D3.

There are four tiny parathyroid glands located on the posterior aspect of the thyroid gland.
Each gland measures approximately $6\,mm$ long by $3\,mm$ wide; they are very small and thin.
Surgical removal of half of these glands (two out of four) typically allows for normal physiological function.
Removal of three out of the four glands generally leads to physiological imbalances.

The primary goal of PTH is to increase serum calcium levels through several distinct mechanisms involving the bones and kidneys:
- Action on Bone: PTH stimulates osteoclast activity. Osteoclasts break down bone tissue, leading to the release of calcium phosphate into the bloodstream. While this releases calcium, it also releases phosphorus.
- Action on Kidneys (Phosphorus Excretion): To maintain the inverse relationship and keep calcium levels high, PTH increases the excretion of phosphorus. This results in decreased serum phosphorus levels and is achieved by decreasing phosphorus reabsorption in the renal tubules.
- Action on Kidneys (Calcium Reabsorption): PTH stimulates the reabsorption of calcium within the kidneys, thereby decreasing the amount of calcium excreted in the urine and increasing serum calcium levels.
- Activation of Vitamin D: PTH triggers the final step of activating Vitamin D3 within the kidney.

Vitamin D3 is the second major hormone that increases serum calcium.
Sources of Vitamin D3:
- Dietary intake.
- In vivo formation: Derived from 7 de hydro cholesterol. This process requires exposure to UV sunlight and involves multiple organs.
Storage: Vitamin D is stored in the liver, adipose (fat) tissue, and muscle. These stores can last for several months.
Deficiency Patterns: In northern climates (such as the northern one-third of the United States), Vitamin D deficiency often develops in the springtime. Storage forms are built up during the summer and depleted over the winter when UV light is insufficient to produce enough pro-vitamin D3. In such cases, supplementation may be necessary based on baseline blood tests.
The activation of Vitamin D3 occurs in two primary steps:
- Step 1: Occurs in the liver.
- Step 2: Occurs in the kidney (largely mediated by the activity of PTH).
Pathological Note: Issues in either the liver or the kidney can prevent the full activation of Vitamin D3.

The most significant action of the active form of Vitamin D3 (125 de hydroxy called Calcium for All) is increasing the absorption of calcium from the intestine.
It plays a regulatory role in the deposition and resorption of calcium salts within the bone.
It mirrors PTH's effect on the kidney by facilitating the excretion of phosphorus and reducing the excretion of calcium.