Diseases that depends on calcium
There are some diseases depends on calcium that we come across in due course of life of ours of our loved once. It is important for everybody to know about those diseases so that we can guess that some thing is wrong we need to consult the condition with a doctor before its to late. In this era maximum human diseases are curable if we diagnose it in earlier stages. That is why basic knowledge about diseases are important for everyone.
Diseases that depends on calcium
Today’s topic is diseases that caused due to abnormality in calcium balance.
- Paget’s Disease
Before we dive into our topic we should have some basic knowledge about calcium metabolism.
What are the roles of CALCIUM in our body?
- Calcium controls nerves and muscles excitability and regulates permeability of cell membranes. It also maintains cell membrane integrity and regulation of cell adhesion.
- Calcium ions are very important for excitation-contraction coupling in all types of muscle and excitation-secretion coupling in all type of glands like exocrine and endocrine glands and also release of transmitters from nerve ending.
- Calcium also acts as an intracellular messenger for hormones and autacoids.
- Calcium controls impulse generation in heart.
- Calcium is factor of coagulation.
- Calcium forms backbone of teeth and bones.
There are 3 hormones which mainly regulate the plasma calcium level. They are Parathormone (PTH) [secreted from parathyroid gland], Calcitonin [secreted from C cells of thyroid gland], Calcitriol [active form of vitamin D]. In addition to these three hormones there are other which also contributes in the regulation of plasma calcium level. They are Glucocorticoids, sex steroids, thyroid hormone, growth hormone.
Now let’s discuss these important hormones in a little bit elaborate form.
Parathormone (PTH): It is a polypeptide hormone of 84 amino acid. It is secreted as a precursor not as active hormone. After their release they shed off extra amino acids in two steps to convert from prepro-PTH to PTH and remain confined in intracellular vesicles. Secretion of PTH depends on plasma calcium level.
For medical students:
There is calcium sensing receptor (CaSR) on the parathyroid gland cells. These receptors measure the plasma calcium level. These receptors are G-protein coupled receptors. When plasma calcium level becomes low then intracellular cAMP level increases and these cAMPs activates phospholipase C this inters release PTH stored vesicles. And reverse is also true. Although direct activation of protein kinase C is physiologically more important. Substances that increase intracellular cAMP will tend to increase secretion of PTH. Prolonged hypocalcemia can cause hypertrophy and hyperplasia and reverse is also true.
- Bone: PTH increases bone resorption. And bone resorption is followed by bone formation. So, low intermittent doses of PTH cause more bone formation than bone resorption.
- Kidney: It has a direct action on distal convoluted tubule of nephron in kidney. It increases calcium absorption from DCT. In hypercalcemia the effect is overridden by excretion of calcium.
- Intestine: PTH have no direct effect on intestine. However, it converts vitamin D in its active form and this active vitamin D increase calcium absorption from intestine.
Note: Teriparatide is the drug similar to PTH hormone. Functions are also similar to that of PTH hormone. Cinacalcet is another drug which is use to reduce the PTH secretion.
Calcitonin: It is a hypocalcemic hormone secreted by `C’ cells of thyroid gland. Synthesis and secretion depend upon plasma calcium level.
Actions: Its actions are just opposite to that of PTH. It inhibits bone resorption by direct action on osteoclast. It also inhibits reabsorption of calcium from Proximal convoluted tubule of nephron of kidney.
Vitamin D3 (Cholecalciferol): Vit. D plays active role in plasma calcium regulation.
Now how do we get vitamin D???
Our first answer should be from diet (fish liver oil), But the major source of vitamin D is not the diet its sunlight. Then how vitamin D develops in our body from sunlight.
In our skin there is 7-dehydrocholesterol. When sunlight falls of this, it converts to cholecalciferol(vit-D3). Then in liver 25-hydroxylation takes place and forms calcifediol(25-(OH)-cholecalciferol). After that 1α-Hydroxylation takes place in kidney and forms Calcitriol(1α,25-(OH)2-cholecalciferol) or simply active form of vitamin D3. This step is the rate limiting step. This step is activated when vit. D level is low or calcium level is low or due to influence of PTH, estrogen etc.
NOTE: Vitamin is considered as a hormone because-
- It is synthesized in body(skin)
- It is transported through blood.
- Feedback regulation of vitamin D occurs by plasma calcium level.
- Increases absorption of calcium and phosphate from intestine. This is done by increasing the number of calcium channels and calcium transporter known as calbindin.
- It increases calcium reabsorption from kidney. But in hypercalcemic states excretion of calcium predominates.
- It enhances resorption of bone followed by bone formation.
For medical students:
It promotes bone resorption by recruiting more osteoclasts by enhancing differentiation. Osteoclast precursors have vitamin D receptors but mature osteoclast doesn’t. But it indirectly activates mature osteoclasts to through RANKL (Receptor for Activation of Nuclear factor-κB-Ligand) secreted by osteoblast cells which have vitamin D receptors. Vitamin D also induce osteoblast cells to laydown osteoid. And also maintain calcium and phosphate plasma level thus it also helps in mineralization indirectly. It also induces production of osteocalcin.
Normal plasma calcium level is 9-11 mg/dl. Of this about 50% are ionized and this 50% is physiologically important, 40% is bound with plasma protein, rest 10% is complexed with citrate, phosphate and carbonate. Acidosis favors more ionization of calcium and alkalosis disfavors. That is why hyperventilation causes tetany, laryngospasm as excess carbon dioxide out of our body so pH of blood rises causing alkalosis. (tetany and laryngospasm are the hypocalcemic conditions)
Now how do they enter in our system and how they are excreted.
Calcium is absorbed in our all the parts of intestine through either facilitated diffusion or a carrier mediated active transport influenced by vitamin D. The rate of absorption is limited by secretion of calcium ion in the ileum.
NOTE: Glucocorticoid, Phenytoin also reduce calcium absorption.
Ionized calcium is filtered in glomerulus and most of it is reabsorbed. Vitamin D and PTH increase its absorption while calcitonin decreases its absorption. In a healthy human being daily 300mg of endogenous calcium is lost half in urine and half in feces. Calcium balance is maintained by taking up calcium from diet. 1/3rd of total calcium in diet is ingested and rest are excreted out. This 1/3rd portion can be extended if calcium in diet is low. For a normal human being calcium allowance in diet is 0.8-1.5 gm per day. Thiazide diuretics hinder calcium excretion.
Different preparations that are used as medicines are:
- Calcium carbonate: Used as antacid.
- Calcium citrate: Used as calcium supplements.
- Calcium gluconate: Used in treatment of tetany.
- Calcium dibasic phosphate: Used as antacid and also calcium supplement.
- Calcium lactate: As supplements.
- Calcium chloride: Soluble form of calcium compound but irritating to stomach.
Calcium supplements have very minimal side effects. They are constipation, bloating, excess gas.
Now come to our main topic calcium related diseases.
- Tetany: It is a hypocalcemic condition in which threshold for action potential decreases because of that muscles undergo repeated contractions (spasms). It may be severe to moderate. In severe cases it is treated with calcium gluconate added with i.v. fluids and oxygen. Some time it may require a long-term oral treatment. In moderate cases, only oral treatment is given.
- Osteoporosis: It is a condition which mainly occurs in post-menopausal woman. As their estrogen level decreases after menopause, their bone resorption predominates and bone becomes porous and weak. So, the chance of fracture increases. The first line drug for osteoporosis are Bisphosphonates (Alendronate), along with this vitamin D and calcium supplement can be given. It does not reduce the chances of bone fracture in the individuals with optimum calcium diet. But it has some benefit if diet is incomplete. Some times in severe osteoporosis another sub-cutaneous inj. is used names Teriparatide. Which is structurally similar with PTH but relatively short chain length.
- Paget’s Disease: It is a disease that disrupts the bone formation after bone resorption. Thus, increasing the chance of more and more fracture. Drug of choice for Paget’s disease is Bisphosphonates. It reduces the rate of bone resorption and also reduce the pain with other symptoms of the disease.
- Hypercalcemia: This is the condition when plasma calcium level becomes high. Symptoms are ectopic calcium deposition, renal stone, weakness fatigue, change in psychiatric behaviors. Treatments are low calcium diet, treatment with Calcitonin, Cinacalcet and
- Hypocalcemia: This is a condition of high plasma calcium level. Symptoms are similar to that of Hypercalcemia. But if it is not corrected it can lead to other diseases like Tetany, Osteoporosis, Osteomalacia, Rickets. It can be corrected by administration of Vit-D, PTH, Bisphosphonates.
- Vitamin D deficiency: It may be due to less exposure to sun or due to inadequate vit-D uptake through diet. As a consequence, PTH is secreted more and more. Thus, Bone resorption predominates and bones become weak and fragile. This leads to rickets in children and Osteomalacia in adults. But protein matrix of bone remains normal. Corrected by administration of exogenous vitamin-D.
- Hypervitaminosis D: It may occur due to chronic ingestion of large doses of vit-D. Manifestations are hypercalcemia, weakness, fatigue, ectopic calcium deposition, sluggishness, polyurea etc. It can be corrected by withholding the Vit-D, low calcium rich diet, lot of fluids with corticosteroids.
- Rickets: This is a disease often seen in malnourished children due to deficiency of calcium. Their bone development is impaired. Bones become deformed and fragile. There are different types of rickets. Like Vitamin D resistant rickets, Vitamin D dependent rickets, Renal rickets, Rickets due to improper nourishment. They can be cured by giving proper nourishment with adequate calcium and vitamin D.
Diseases that depends on calcium
penned - Debojit dey