.

INTRODUCTION
• Minerals are inorganic compounds that are
essential for the normal growth and maintenance
of the body.
MINERAL METABOLISM • The inorganic elements (minerals) constitute
only small proportion of the body weight.
BY:-
DR. SUNITA SINGH • Human body needs a number of minerals for
Assistant Professor, Dept. of Biochemistry
its functioning.
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FUNCTIONS CLASSIFICATION OF MINERALS

Minerals perform many vital functions which are
Macro
essential for existence of organism- Micro minerals
1. Calcification of bones
minerals
2. Blood coagulation Required in Required in
excess of amounts less than
3. Neuromuscular irritability 100mg/day 100mg/day
4. Acid-base equilibrium
Ca++, P, S, Mg, Fe, Cu, Zn, Mo, I,
5. Fluid balance Cl, Fl,
6. Osmotic regulation Na, K. Cr, CO, Mn
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• The most abundant mineral found in human

CALCIUM
body is Calcium.
• Total Calcium in human body: 1 – 1.5 Kg
• In Bones – 99 %
• In extra cellular fluid – 1 %

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• Milk is a good source for calcium.

• Milk (Cow’s Milk–100mg/100ml)

- Egg, Fish, Vegetables - moderate

- Cereals (wheat, rice) - poor source

Children Adults Pregnancy
and
(1-18years) (men & lactation
women) 1500mg/day
1200mg/day
500mg/day

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ABSORPTION Factors affecting Calcium absorption

• Dietary calcium is absorbed in duodenum by
Calcium absorption is increased by-
active process. 1. Calcitriol is the active form of vitamin D. It

• Absorption requires a carrier protein, helped by
Calcium- dependent ATPase.
• Out of the 500 mg of calcium taken orally per
day, 400mg is excreted in stool and 100 mg is
excreted through urine.
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increases the blood calcium and promotes Ca
absorption.
2. PTH enhances Ca absorption through increased
synthesis of Calcitriol.
3. Low ph (acidic) is favourable for Ca absorption.
4. Lysine and arginine increases Ca absorption.
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Calcium absorption is decreased by- Functions of Calcium

1. Phytates and oxalates - form insoluble calcium  GROWTH OF BONE & TEETH-

oxalates • The bulk quantity of calcium is used for bone and teeth
formation. Bones also act as reservoir for calcium in the
2. High dietary phosphates - precipitate as calcium body. Osteoblasts induces bone deposition and osteoclasts
phosphate produce demineralization.
 MUSCLE CONTRACTION-
3. High pH - (alkaline)
Calcium mediates excitation and contraction of muscle
4. High dietary fiber fibers. Calcium interacts with troponin C to trigger muscle
5. Mal absorption syndrome - Fatty acids not absorbed contraction. It also activates ATPase, increases the
interaction between Actin and myosin.
and form insoluble calcium salts of fatty acid.

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BLOOD COAGULATION-  CALCIUM AS INTRACELLULAR MESSENGER-

• Calcium is known as factor IV in blood coagulation
cascade.
• Prothrombin → Thrombin
 NERVE CONDUCTION-
• Calcium is necessary for transmission of nerve
impulses from presynaptic to postsynaptic region.
 SECRETION OF HORMONES-
• Calcium mediates secretion of insulin, parathyroid
hormone, calcitonin, vasopressin, etc. from the
cells.
• Calcium and cyclic AMP are second messengers of
different hormones Eg: Glucagon.
ACTIVATION OF ENZYMES-
• Calcium is needed for the direct activation of
enzymes such as pancreatic lipase and succinate
dehydrogenase.
• Calmodulin is a Calcium binding regulatory protein.
Calmodulin can bind with 4 calcium ions. It is part of
various regulatory kinases. e.g., Pyruvate kinase etc.

ACTION ON HEART- PLASMA CALCIUM

• Ca++ acts on myocardium and prolongs systole. • Most of the blood Ca is present on plasma whereas

• In hypercalcemia, cardiac arrest is seen in systole. content of Ca in blood cell is very little.
NORMAL RANGE- %
• ↑ Ca concentration → ↑ myocardial contractility
Plasma calcium 9 to 11mg/dl
VASCULAR PERMEABILITY- 10%
Free or
ionized
Urine calcium: 100-250 mg/day calcium
• Calcium decreases the passage of serum through Protein
Calcium in plasma is of 3 types bound
capillaries. 40%
50%

• Ionized or free or unbound calcium complex

• Calcium is clinically used to reduce allergic with
exudates. • Bound calcium anions

• Complexed calcium
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Homeostasis of Calcium
• The major factors that regulate the plasma
Calcium
Calcitriol
Gut
 Calcitriol
3 PTH
3
Bone
Organs
Hormones  Parathyroid hormone
Kidney
Calcitonin  Calcitonin

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ROLE OF CALCITRIOL
1) On Intestine:
• Calcitriol (dihydroxycholecalciferol) increases
intestinal absorption of Ca2+ & phosphate.
• Calcitriol enters the intestinal cell and binds to a
cytoplasmic receptor.
• Complex interacts with DNA leading to the
synthesis of a specific calcium binding protein.
• This protein increases calcium uptake by
intestine.
3) On Kidneys:
• Calcitriol increases the reabsorption of calcium
and phosphorus by renal tubules, therefore, both
minerals are conserved.
ROLE OF PARATHYROID HORMONE
1)Action on the bone:
• PTH causes decalcification or demineralization
of bone, a process carried out by osteoclasts.
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• PTH promotes the production of calcitriol (1,25
DHCC) in the kidney.
3) On Intestine:
• It increases the intestinal absorption of Ca2+ by
promoting the synthesis of calcitriol.
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.
2) On Bone:
• Calcitriol (Vitamin D) is acting independently
on bone. Vitamin D increases the number and
activity of osteoblasts. In osteoblasts of
bone, calcitriol stimulates calcium uptake for
deposition as calcium phosphate.
• It also stimulates secretion of alkaline
phosphatase.
• Due to this enzyme, calcium and phosphorus
increases, leading to mineralization.
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• This is brought out by pyrophosphatase &
collagenase.
• These enzymes result in bone resorption.
• Demineralization ultimately leads to an
increase in the blood Ca2+ level.
2) On Kidneys:
• PTH increases the Ca2+ reabsorption by kidney
tubules
• It is most rapid action of PTH to elevate blood
Ca2+ levels.
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ROLE OF CALCITONIN
• Calcitonin is a peptide containing 32 amino acids.
• It is secreted by parafollicular cells of thyroid gland.
• The action of calcitonin on calcium is opposite to that
of PTH.
• Calcitonin promotes calcification by increasing the
activity of osteoblasts.
• Calcitonin decreases bone resorption & increases the
excretion of Ca2+ into urine
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Calcitonin has a decreases blood calcium level.
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HEMOSTASIS OF CALCIUM

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Stools Urine Sweat

Unabsorbed
calcium in
the diet 50-200mg/day 15mg/day
60 – 70%

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Causes
1. Primary hyperparathyroidism
Increased serum Ca2+ level >11 mg/dl
- Tumors
- Ectopic source (MEN I, MEN II)
2.Malignancy
Causes Features Treatment
- Humoral hypercalcemia of malignancy
- Direct involvement of bone
- Hematological malignancies
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3. Granulomatous disease Symptoms

- Tuberculosis, sarcoidosis
1. Anorexia, nausea, vomiting
4. Overdose of vitamins
2. Polyuria and polydypsia (ADH antagonism)
- Intoxication of vit A, hypervitaminosis D
5. Drug-induced Hypercalcemia 3. Confusion, depression, psychosis
- Thiazide, spironolactone 4. Renal stones
6. Misc 5. Ectopic calcification and pancreatitis
- Idiopathic hypercalcemia of infancy
6. Blood alkaline phosphatase is increased.
- Increased serum proteins

Management
• Adequate hydration, IV normal saline
Decreased serum Ca2+ < 8.8 mg/dl
• Furosemide IV to promote calcium excretion

• Steroids, if there is calcitriol excess

• Beta blockers in thyrotoxicosis Causes Features Treatment

• Definitive treatment for the underlying
disorder.
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Causes Symptoms
1. Deficiency of vitamin D
1. Muscle cramps
2. Hypoparathyroidism
- Surgical-induced 2. Paresthesia, especially in fingers

- Autoimmune 3. Neuromuscular irritability, muscle twitchings

- Hypoparathyroidism of infancy 4. Tetany (Chvostek’s sign, Trousseau’s sign)
3. Renal failure
5. Seizures
4. Hypoalbuminaemia
6. Bradycardia
5. Acute pancreatitis
6.Magnesium deficiency 7. Prolonged QT interval

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Treatment Tetany:
- Accidental surgical removal of parathyroid glands
1. Oral calcium, with vitamin D supplementation
- Autoimmune diseases.
2. Underlying cause should be treated
- Neuromuscular irritability is increased.
3. Tetany needs IV calcium (usually 10 mL 10% Symptoms:
calcium gluconate over 10 minutes, followed - Carpopedal spasm
by slow IV infusion. - Laryngismus and stridor

• IV calcium should be given only very slowly. - Chvostek’s sign (tapping over facial nerve causes
facial contraction)

- Trousseau’s sign (inflation of BP cuff for 3

minutes causes carpopedal spasm)
- Increased Q-T interval in ECG is seen.
- Serum calcium is ↓ , phosphate level ↑.
- Urinary excretion of both calcium and
phosphate ↓.
Treatment:
- Intravenous injection of calcium salts.

• An increase in the activity of alkaline

• Rickets is a disorder of defective calcification phosphatase is a characteristic feature of
of bones. rickets.
• This may be due to a low levels of vitamin D in
the body or due to a dietary deficiency of Ca2+
& P or both.
• The concentration of serum Ca2+ & P may be
low or normal.
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Osteoporosis • Decreased absorption of vitamin D & reduced

• Characterized by demineralization of bone levels of androgens/estrogens in old age are the
resulting in the progressive loss of bone mass. causative factors.
• After the age of 40-45, Ca2+ absorption is Osteopetrosis
reduced & Ca2+ excretion is increased; there
• Marble bone disease.
is a net negative balance for Ca2+
• ↑ bone density.
• After the age of 60, osteoporosis is seen.
• There is reduced bone strength & an • Mutation in gene of carbonic anhydrase type II.
increased risk of fractures. • Inability of bone resorption by osteoclasts.
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Paget’s Disease
• Localized disease, characterized by osteoclastic
bone resorption
• Disordered replacement of bone.
• Common in people above 40 and may affect
one or several bones.
• Familial incidence
• Treatment - Bisphosphonates.
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PHOSPHORUS
• Human body contains - 1 kg of phosphorous
• Body distribution:

85% of phosphorous is found in bones & teeth in
combination with calcium.

14% of phosphorous is present in soft tissues, as a
component of
phospholipids, phosphoproteins, nucleic
acids & nucleoproteins.

1% is found in ECF, as inorganic form
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Sources Functions of Phosphorus

• Cheese, milk, nuts, organ meats, egg
• Milk is the best source (contains about 100 mg/dL
phosphate)

Requirement: 500 mg/day

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ABSORPTION Normal levels:

• 90% of dietary phosphorous is absorbed in
• In serum:
JEJUNUM
 Adults - 3 - 4 mg/dL
• Stimulated by both PTH and Vit. D
• The Ca:P ratio in diet affects the absorption  Children - 5 - 6 mg/dL
and excretion of phosphorus.  There’s a postprandial decrease of phosphorus
Regulation: • In whole blood:
• Kidneys  Total phosphate – 40 mg/dL
• GI tract  RBC and WBC stored the maximum amount
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Causes of hyperphosphatemia
1. Increased absorption of phosphate
Excess vitamin D, phosphate infusion
2. Increased cell lysis
Chemotherapy for cancer, bone secondaries,
Rhabdomyolysis
Hypophosphatemia 3. Decreased excretion of phosphorus
Hyperphosphatemia Renal impairment, hypoparathyroidism
4. Hypocalcemia
5. Massive blood transfusions
6. Thyrotoxicosis
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7. Drugs - Chlorothiazide, Nifedipine, Furosemide.

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Causes of hypophosphatemia
1. Decreased absorption of phosphate
Malnutrition, malabsorption, chronic diarrhea,
vitamin D deficiency
2. Intracellular shift
Insulin therapy, glucose phosphorylation
3. Increased urinary excretion of phosphate
Hyperparathyroidism, fanconi’s syndrome,
hypophosphatemic rickets
4. Hereditary hypophosphatemia
5. Hypercalcemia
6. Chronic alcoholism
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7. Drugs - Antacids, Diuretics, Salicylate intoxication

Iron
• Blood contains 14.5 g of Hb per 100 mL.
• Most essential trace elements in the body
• About 75% of total iron is in hemoglobin, and
• Total iron content in a human – 3.0 gm to 5.0 gm
5% is in myoglobin and 15% in ferritin.
• Iron is present in almost all cells.
• Non- heme iron containing proteins :
• Heme containing proteins:
ferritin, transferrin, hemosiderin, aconitase,
Hb, myoglobin, cytochromes, cytochrome
phe- hydrolase & neutrophils.
oxidase, catalase, peroxidase, xanthine oxidase &
Trp pyrrolase.

Green
leafy Egg Pulses Adult Pregnancy
vegetables
20
Liver and
Jaggery Cereals
mg/day 40mg/day
meat

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Site Forms Efficiency

Heme About
Absorption Transport Storage Excretion
10% of
Duodedum total food
Non- iron is
haem absorbed

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ABSORPTION OF IRON
• Absorbed by upper part of duodenum
Factors increasing iron absorption • Homeostasis is maintained at the level of
Ferrous form Ascorbic acid Cysteine HCl absorption by mucosal block theory
• Iron stores depleted - absorption ↑
• Iron stores adequate - absorption ↓
Factors decreasing iron absorption
Antacid,
• Only Fe++ (ferrous) form is absorbed and not
Phytates and Gastrointestinal
phosphate achlorhydria diseases Fe+++ (ferric)
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• Ferrous Iron binds to mucosal cell protein called • Ferric Iron is released, reduced to Ferrous state
Divalent Metal Transporter - 1 (DMT-1).
crosses the cell membrane.
• This bound Iron is then transported into the
In the blood stream
mucosal cell.
• Reoxidized to Ferric state by Ceruloplasmin
• Unabsorbed Iron is excreted.
• Ferric Iron bound with Transferrin and
Inside the mucosal cell
transported to tissues.
• Iron oxidized to ferric state.

complexed with apoferritin to form Ferritin.

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Lumen Mucosal cell Blood

Ferroreductase
Ferric Iron
Fe+++ Fe++ Fe++
Ferritin • Regulation of Absorption by Four Mechanism

Ceruloplasmin
Ferric reductase

Vit C i. Mucosal regulation

ii. Stores regulation
Apoferritin
Fe+++ - ↓ iron store, ↑ absorption
Fe++ Fe+++

Apotransferrin
Ferrous Iron
Fe++ Ferroxidase
iii. Erythropoietic regulation
- Anaemia provides a signal for increase mucosal
absorption
Transferrin
Heme iron
Heme iron Fe+++ iv. Regulation at the level of transcription
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Storage Site
Bone
Liver Intestine Spleen
marrow

Storage Form
Ferritin Hemosiderin
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Conservation of iron in the body

Normal Physiological
Stool
excretion loss

Menstruation
Very little
20-30mg/cycle
0.7mg/day
About Delivery
1mg/day 750mg

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Iron
deficiency Iron excess

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Decreased Increased
Decreased Increased
absorption of iron
intake of iron loss of Iron
iron requirement

Lab
Causes Features Treatment
findings Achlorhydria Bleeding,
Pregnancy,
Malnutrition and chronic hookworm
infancy
diarrhea infestation

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Decreased hemoglobin

Pallor Dizziness Palpitation Pica Microcytic hypochromic anemia

Angular Decreased serum iron

Fatigue Dyspnea
stomatitis
Increased serum total iron binding capacity

Decreased plasma ferritin

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Treatment of underlying causes Haemosiderosis Haemochromatosis

Treating Administration of iron preparations Increase in iron Excessive

Hookworm stores as deposition of iron
haemosiderin in the tissue

Controlling Orally I.V Without

Associated with
bleeding associated with
tissue injury
tissue injury
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Lab findings

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