MINERALS IN HUMAN HEALTH

In the introductory session About 28 minerals have some role in human development and health. Major elements or Macro minerals are 7 ( Ca, P, Mg, Na, K, Cl, and S ) Micro or trace elements are 11 (I, Fe ,Co, Cr, Cu, Mo, Mn , Se, Ni,Zn and F)

Role of Calcium in Health of Bones

At.No.20 Calcium At .Wt 40

Learning Outcomes Distribution in the body Important functions Dietary sources Daily Requirements Absorption

BONES AND SKELETON Higher animals have an internal frame work – endoskeleton Skeleton is made almost entirely of a hard, rigid tissue – bone Bone consists (like other living tissues) of living cells suspended in an inert ground substance

GROUND SUBSTANCE OF BONES is The determining factor of bone characteristic properties Network of protein fibers with insoluble mineral salts Mostly phosphate of calcium. Responsible for hardness of bone

BONE GROWTH Bone grows by the activity of osteoblasts. These have enzyme which separates Insoluble calcium phosphate from soluble phosphate in blood by precipitation These enzymes also synthesize special proteins Viz,  osteocalcin and osteopontin,

Osteoblast will do their work only if the essential elements of bones are present in diet in reasonable quantity. These are Ca, P, Vit. D, Vit. A , Proteins, PTH and Calcitonin Proper absorption of dietary essential by GIT which depends on many factors. Also intact Kidneys are required

Distribution of Ca in the human body An adult human body contains about 1-1.5 Kg of calcium. 99 % of it is present in bones and teeth as insoluble crystalline mineral hydroxy-apatite. 1% is in blood and ECF and soft Tissues.

Chemically [{Ca3(po4)2}3.Ca(OH)2] 1% is present in blood,ECF and soft tissues Chem formula of bone is Ca10(PO4)6(OH)2 6 HPO42− + 2 H2O + 10 Ca2+ ⇌ Ca10(PO4)6(OH)2 + 8 H+

Distribution 0.03% of Total Body calcium in blood Normal Serum / plasma contains 9 – 11 mg/dl RBCs contain very little Ca++ Ca++ in bone is constantly exchanged with that of interstitial fluid Regulated by PTH, Vit - D3 and calcitonin

In plasma Ca++ occurs in two forms 1. Diffusible a. Ionized almost 50% 5.45 – 6.23 mg/dl Physiologically active  Hyperparathyroidism  Hypoparathyroidism If level drops to 4.3 mg/dl Tetany occurs

In plasma Ca++ occurs in two forms 2. Non diffusible 40% 3.4 – 4.4 mg/dl Combined with plasma proteins (Albumin) Not dialyzable Low in hypoproteinemia

3. Complexed Calcium about 5-10% Complexed with Citrate or phosphate. This is also diffusible form. All the three forms remain in equilibrium in health.

Functions 1. Calcium salts take part in bone and tooth development . Deficient supply of calcium leads to rickets in children and osteomalacia in adults. Sufficient calcium intake must be ensured in early life to buildup the skeletal reserves.

Consequences If this is not done, then there occurs an increased incidence of osteoporosis in old age because at that time deficiency of sex hormones especially in females results in calcium mobilization from bones leading to osteoporosis

Function 2. The clotting of blood needs calcium ions. Calcium is known as factor iv in blood coagulation cascade. Prothrombin contains gamma carboxyl glutamate residue which are chelated by calcium during the thrombin formation.

Function 3- By regulating the membrane permeability Ca++ control the excitability of nerves. If plasma Ca++ level falls markedly, tetany results in which spasms of various muscle groups occur. Death may occur from convulsions or from laryngospasm. Excess of plasma Ca++ depresses nervous activity.

Function 4- Calcium ions act as a cofactor or activator of certain enzymes. A protein namely calmodulin is present within cells which can bind calcium.

calmodulin-calcium complex Becomes attached to certain enzymes which are activated. Such enzymes include adenylate cyclase. Ca++ ATPase , phosphorylase kinase, myosin light chain kinase, phosphodiesterase and phospholipase A 2. This mechanism also is required for the release of acetylcholine at the neuromuscular junctions.

Functions 5- Calcium ions take part in the contraction of muscle including heart muscle and are involved in the excitation- contraction coupling mechanism. With an increased plasma calcium, heart stops in systole (calcium rigor)

Functions In addition, a high plasma calcium decreases conduction of cardiac impulses and thus can produce heart block. Calcium ions potentiate the effects of cardiac glycosides and therefore should not be given to patients who are using these drugs.

Functions Calcium is essential for maintaining the integrity of capillary wall. in its deficiency, capillary walls become fragile and there is increased permeability of capillaries .In a similar manner it has a role maintaining the integrity of mucosal membranes and cell adhesion.

Function 6- Calcium ions are involved in exocytosis and thus have an important role in stimuls-secretion coupling in most exocrine and endocrine glands e.g the release of catecholamines from the adrenal medulla, and histamine from mast cell are dependent upon Ca++ .

Functions 7- Some hormones exert their influence through Ca++ . For example, the effect of adrenaline on the liver cells to increase glycogenolysis is partly due to an increased Ca++ within these cells .

Functions Calcium ions are responsible for initiating contraction in vascular and other smooth muscles. Calcium ions enter through specific channels just as is the case with cardiac muscle. Drugs which block these channel (Ca++ channel blockers) have profound effect on the contractility of cardiac and smooth muscles as well as on the conduction of impulses within the heart. These drugs find use in treatment angina pectoris, cardiac arrhythmias and hypertension.

Dietary sources Milk and Dairy products Hard cheese concentrated source Cottage cheese and ice cream Egg, yolk, leafy vegetable Water

Dietary sources Shrimps, oysters and salmon Mustard green, turnip and spinach Whole wheat bread Inorganic salts CaCl2, CaCo3

Dietary sources When diet is deficient : salts of Calcium with carbonate, gluconate, lactate, Sulphate may be taken as supplement Milk and milk products: 2 – 3 cups /day - Adults 3 – 4 cups/day - Children

Recommended Dietary Allowance Infants 0 – 0.5 years 360 mg. 0.5 – 1.0 540 Children 1 – 3 800 4 – 6 800 7 – 10 800

Recommended Dietary Allowance Male / Females 11 – 14 1200 15 – 18 1200 19 – 22 800 23 – 50 800 51+ 800 Pregnancy +400 Lactation +400

Absorption Both organic and inorganic forms of Ca++ are utilized and absorbed Mostly in proximal part of small intestine

Absorption Calcium is absorbed against a concentration gradient and requires energy. Requires a carrier protein Helped by calcium dependent ATP ase.

Absorption Absorbed by active transport mechanism in two steps Uptake of calcium through Ca++ specific channels Efflux – Ca++, Mg++ and ATPase Some absorption through passive transport / facilitated diffusion

Intestinal absorption • In a balanced diet, roughly 1000 mg of Ca is ingested each day and about another 200 mg/day is secreted into the GI tract in the bile and other GI secretions.

Depending on the concentration of circulating vitamin D, particularly 1,25(OH)2 D (1,25 Dihydroxycholecal ciferol, Calcitriol, or active vitamin D, roughly 200 to 400 mg of Ca is absorbed from the intestine each day.

EXCRETION The remaining 800 to 1000 mg appears in the stool. Ca balance is maintained through renal Ca excretion averaging 200 mg/day.

THANKS

Factors affecting calcium absorption Vitamin – D Increases the absorption of calcium Increase the specific transport protein responsible for active transport of calcium in proximal small intestine wall

Factors affecting calcium absorption 2. PTH  calcium absorption but effect is less marked than vitamin D 3. Calcium : P when 1 : 2 or 2 : 1 in food optimum absorption 4. Excess of Po4 in GIT  calcium absorptio 240 mg Ca++ absorbed/day

Presence of FFA Excessive fat intake lowers Ca absorption . Due to impairment in absorption , free fatty acid react with free calcium and forms insoluble complex ( Ca-soaps) Bile salts increase absorption of Ca++ by properly absorbing FFA & prevents formation of Ca-complexes

Presence of Anions Oxalates, carbonates and sulfates inhibit Ca++ absorption as Ca complexes with these are insoluble Ca++ salts with chloride , glucose and lactate are soluble & absorbed to greater extent. Ca++ salts with AA from proteins taken in diet, are more soluble in aq. Solutions of AA & thus facilitate Ca++ absorption.

Intestinal pH. Ca++ is well absorbed in acidic medium .If pH is low, calcium salts are more soluble.

Calcium Deficiency If the body is deficient in Calcium, then increased absorption and this is mediated through an increased parathyroid activity

Less calcium is absorbed in old age

Intestinal Disease like Malabsorption , Ceolic Diseases , and Steathorea decrease Ca++ absorption Idiopathic hyper calcaemia ,Ca++ absorption from intestine is greatly increased due to unknown reasons.

Amount of calcium absorbed from the GIT Parathyroid hormone Like increasing intestinal absorption of calcium, also mobilizes bone calcium and causes marked hypercalcemia. It also increases calcium absorption from the distal convoluted tubules of the kidney.

Inverse relationship between plasma calcium and inorganic phosphate (Pi) level When plasma calcium rises, the plasma inorganic phosphorus level falls and vice versa. The product of plasma calcium and inorganic phosphorus (both in mg/dl) remains constant at 30 to 40 in the adult and 40 to 55 in children. 1

Plasma calcium level falls in kidney diseases due to retention of phosphate, which leads to a high plasma Pi level and hypo-calcemia. The other contributory factor is non-activation of vitamin D. The hypo-calcemia leads to secondary hyper parathyroidism

Plasma protein level Each gram of plasma/serum protein binds 0.84 mg of calcium. Thus a decrease in serum protein level (i.e. hypoproteinemia) will result in a decreased level of bound calcium and will also result in a lowered total serum calcium.

Plasma protein level As the ionized serum calcium remains normal, therefore such a person will not suffer tetany because it is only the ionized calcium which is physiologically active.

Renal excretion. Normally only a small part of calcium lost from the body is excreted in urine. If excessive amount of calcium are administered, more Na+is being excreted in urine, Renal loss of calcium is also increased if more Na+ is being excreted e.g. by diuretics.

Calcitonin Produced by the para follicular cells (clear or C cells) of the thyroid gland. It lowers the plasma Ca++ level, (it antagonizes the action of PTH ) It decreases bone re-sorption and increases the deposition of Ca++ in bones. It increases urinary loss of Ca ++ by inhibiting the Ca++ re-absorption in the proximal convoluted tubules.

Toxicity of calcium Excessive intake of calcium can be dangerous because calcium gets deposited in various body tissues resulting in their malfunctioning .This effect of hypercalcemia is seen more frequently if serum Pi level is normal or raised.

Calcium excretion Daily 1240 mg calcium enters the gut, 1000 mg from food and 240 mg from the blood; of this 480 mg is absorbed showing a net absorption of 240 mg. Feces eliminate 760 mg calcium day which represents the unabsorbed dietary calcium along with calcium coming from the blood.

Calcium excretion Of the 6000 mg calcium filtered by the glomeruli most of it is reabsorbed and the kidneys excrete only 240 mg calcium /day which represents the real excretion of calcium from the body..

Calcium excretion Normally only a negligible amount is lost from the skin but excessive sweating result in an appreciable loss of body calcium.

Calcium excretion Pregnancy and lactation result in a significant loss of mother’s calcium

Calcium balance It is the difference between the quantity of calcium ingested and lost from the body over a certain period of time. If the quantity of calcium lost from the body is less than that ingested, the balance in called positive. If more calcium is lost than ingested, it is called a negative calcium balance.

Conditions associated with a positive calcium balance. Growth Hyperpituitarism involving growth hormone Pregnancy 4. Calcium intake after a long period of calcium deprivation

Kidneys filters out calcium Calcium is absorbed by GIT Soft tissue Calcium Extra Cellular Fluid Calcium in Bone Kidneys filters out calcium