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MINERALS

Dr. B. P. Galhena
Dept. of Biochemistry and Clinical Chemistry,
Faculty of Medicine, University of Kelaniya
Objectives

• Minerals required for human health


• Biological significance of minerals
• Daily requirement and dietary sources
• Absorption and transport in blood
• Assessment in serum
• Deficiencies and overload
• Intervention to overcome deficiencies
Minerals
Macro Minerals Trace Elements (Micro Minerals)
(< 100 mg/day)
(> 100 mg/day)
Na+, K+, Ca 2+, Mg2+ , P Fe, I, Cu, Mn, Zn, Co, Cr3+ , Mo, F, Se
Sources of minerals in the food guide pyramid
Supplementation vs. Fortification of Nutrients

Recommended Nutrient Intake (RNI) is the daily intake


that meets the almost all the nutrient requirements of
a healthy adult individual.
Upper tolerable nutrient intake level is the maximum
intake of certain nutrients which does not result in
toxicity.
Some nutrient may exert protective effect when
exceeding RNI – Protective Nutrient Intake
In most of the cases RNI is not met indicating either
supplementation of fortification.
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Balancing the Deficiency and Toxicity

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Fortification is addition of nutrient/s to commonly eat
food (the vehicle); cost effective, successfully
implemented. Eg: Iron fortification of wheat flour,
Iodine fortification of table salt.

Supplementation refers to periodic administration of


pharmacologic preparations of nutrients as capsules or
tablets or by injection when substantial or immediate
benefits are necessary for the group at risk. Not a
sustainable practice on community based approach.

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Concept of a balanced diet; Improving the
Recommended Nutrient Density (RND)
Nutrient profiling is an indication of the nutrient
contents of each food items. This is quantitatively
expressed as Nutrient Density.
Nutrient density of a given diet can be improved
by adding number of food items with different
nutrient densities; introduced as balanced diet.
Certain food items may be either energy dense
and some may nutrient dense. Therefore,
appropriate combinations are useful in having
well balanced diet.
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Macrominerals
2+
Calcium (Ca )
• Abundant in bones and teeth (99%)
• Balance in soft tissues and extracellular fluids (<10 g)
Recommended daily requirement
Infants and children - 500- 600 mg/day
Adolescent (10 – 18 yrs) - 1300 mg/day
Adult - 1000 mg/day
Pregnancy & lactation - 1000-1200 mg/day
Tolerable upper limit - 4000 mg/day

Extra calcium is needed in


Menopausal Woman
Amenorrheic Women and the Female Athlete Triad
Lactose Intolerant Individuals
Vegetarians
Macrominerals

Biological Significances

● Development of bones and teeth


● Maintain excitability of neuromuscular junctions
● Blood clotting
● Action of complement
● Regulate permeability of membranes
● Mediate action of several hormones
● Activation of enzymes e.g. succinate dehydrogenase
● Need for secretion of many hormones e. g. insulin
● Muscles contraction
Macrominerals
Dietary sources

1. Milk and milk products; butter, cheese, curd


Cow milk - 120 mg/100ml
Human milk - 30 mg/100ml ( bioavailability high)
2. Small fish and canned fish
3. Legumes : beans, yellow dhal
4. Dark green leafy vegetables

CALCIUM BALANCE:
It is the net gain or loss of calcium by body over a specific period of time.
Amount absorbed = Amount ingested - Amount egested in faeces
Amount retained = Amount absorbed – Urinary calcium( excreted)
Macrominerals
Calcium metabolism

Overview of calcium exchange between different tissue compartments in a person


ingesting 1000 mg of calcium per day. Note that most of the ingested calcium is
normally eliminated in the feces, although the kidneys have the capacity to excrete
large amounts by reducing tubular reabsorption of calcium.
Macrominerals
Calcium Absorption
Ca+2 is poorly absorbed from intestine.
•Vitamin D and PTH promotes absorption
•Slight acidity or neutral pH is needed for Ca absorption

Active transport – Where Ca absorption occurs against


Ca concentration and is dependent on 1,25 dihydroxycholecalciferol -
Duodenum
Passive diffusion occurs lower down in the small intestine and accounts
only for 15%.

Factors affecting absorption :


•pH of intestinal contents: acidic pH – favors, alkaline medium - lowered
•Composition of diet: High protein diet favors absorption
Fatty acids – decreases absorption, Sugars and organic acids
Citric acid also increases absorption- chelator
Phytic acid, oxalate forms insoluble calcium salts

Minerals : Excess phosphates lowers calcium absorption


Macrominerals
Calcium Homeostasis
serum Ca

Parathyroid gland

PTH levels
- ve

Kidney Calcitriols Bone


Ca reabsorption from tubules
Ca excretion Intestine

Phosphate excretion Ca
Ca absorption mobilization

Plasma Ca
Macrominerals

Etiologies of Hypocalcemia
Decreased GI Absorption
Poor dietary intake of calcium
Impaired absorption of calcium
Vitamin D deficiency
Decreased conversion of vit. D to calcitriol
Liver failure
Renal failure
Decreased Bone Resorption / Increased Mineralization
Low PTH (hypoparathyroidism)
PTH resistance (pseudohypoparathyroidism)
Vitamin D deficiency / low calcitriol
Increased Urinary Excretion

Deficiency disorders
Tetany, Rickets, Osteoporesis
Macrominerals
Etiologies of Hypercalcemia
● Increased GI Absorption
● Milk-alkali syndrome
● Elevated calcitriol
● Vitamin D excess
● Increased Loss From Bone/ Increased net bone resorption
Elevated PTH - Hyperparathyroidism

● Malignancy
Osteolytic metastases
PTHrP secreting tumor
squamous cell bronchogenic carcinoma.
● Increased bone turnover Paget’s disease of bone Hyperthyroidism
● Decreased Bone Mineralization
Elevated PTH
Aluminum toxicity

● Decreased Urinary Excretion


● Thiazide diuretics Elevated calcitriol Elevated PTH
Macrominerals
Phosphorus (P)
● 80-85 % in skeleton combined with Ca as hydroxyapatite
ECF mostly
Balance inorganic HPO42-,
(15-20% H2PO4-
) Intracellular organic compounds,
PL, Phosphoprotein, nucleic acid
Recommended daily requirement
Infants (0 – 12 moths) - 240- 400 mg/day
Children (1-15 yrs.) - 800-1200 mg/day
Adult - 800 mg/day
Pregnancy & Lactation - 1200 mg/day
Tolerable upper limit - 4000 mg/day
Macrominerals

Biological Significances

● Development of bones and teeth


● Cell signaling
● Assist in enzyme activity - glycogen phosphorylase
● Formation of phospholipids
● Formation of nucleic acid
● Formation of high energy compounds - ATP
● Formation of coenzymes -NADP
● Help in buffering action of cells
Macrominerals
Dietary Sources
Food Serving Phosphorus (mg)
Milk, skim 8 ounces 247

Yogurt, plain nonfat 8 ounces 385

Cheese, mozzarella; part


1 ounce 131
skim

Egg 1 large, cooked 104


Beef 3 ounces, cooked* 173
Chicken 3 ounces, cooked* 155
Turkey 3 ounces, cooked* 173
Fish, halibut 3 ounces, cooked* 242
Fish, salmon 3 ounces, cooked* 252

Bread, whole wheat 1 slice 57

Bread, enriched white 1 slice 25

Carbonated cola drink 12 ounces 40

Almonds# 1 ounce (23 nuts) 134


Peanuts # 1 ounce 107
Lentils # 1/2 cup, cooked 178

Phosphorus from nuts, seeds, and grains is about 50% less


bioavailable than phosphorus from other sources.
Macrominerals
Phosphorus Absorption
Simple diffusion -duodenum
Active transport – ileum
Regulation
Phosphorus Homeostasis Macrominerals

serum phosphorus

hydroxylase
Kidne 1,25 DHCC
y (Calcitriols)

Intestin Bone
e
Ca excretion Ca & P absorption Mobilization Ca &
Due to absence of P
PTH

Plasma Ca &
P
Macrominerals
Causes for Hyperphosphatemia

Increased GI Intake
Fleet’s Phospho-Soda

Decreased Urinary Excretion


Renal Failure
Low PTH (hypoparathyroidism)
s/p thyroidectomy
s/p I131 treatment for Graves disease of thyroid cancer
Autoimmune hypoparathyroidism
Cell Lysis
Rhabdomyolysis
Tumor lysis syndrome
Macrominerals
Causes for Hypophosphatemia
Decreased GI Absorption
Decreased dietary intake (rare in isolation)
Diarrhea / Malabsorption
Phosphate binders (calcium acetate, Al & Mg containing antacids)

Decreased Bone Resorption / Increased Bone Mineralization


Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases

Increased Urinary Excretion


Elevated PTH (as in primary hyperparathyroidism)
Vitamin D deficiency / low calcitriol
Fanconi syndrome

Internal Redistribution (due to acute stimulation of glycolysis)


Refeeding syndrome (seen in starvation, anorexia, and alcholism)
During treatment for DKA
Macrominerals

Magnesium (Mg 2+)

• Magnesium is 4 th most abundant cation in the body


• Approx. 50% in bones and Balance in intracellular
organelles and ECF
• Concentrated in mitochondria and chloroplast
• Daily requirement 300mg/ day
• Dietary Sources - Rich in meat and visera, green leafy
vegetable, Poor in milk
Macrominerals
Biological Significances

• Constituent in bones and teeth


• Neuromuscular transmission
• Co factor > 300 enzymes
• Interaction of actin and myosin (muscle contraction)
• Protein folding
• Intracellular signaling
• Component of active ATP molecule

Deficiency disorders
Neuromuscular disturbances, Osteoporosis, Fatigue and
Muscular weakness, asthma etc.
Trace Elements

Iodine (I)
Biological Significances
• Synthesis of Thyroid hormone (T3 and T4)
Daily requirement
Adult - 100-150 μg/day
Infants - 20-40 μg/day
Pregnancy - 125-175 μg/day
Tolerable upper limit- 1100 mg/day

Food sources
Salt, Sea food, Fruits & Vegetables grown in coastal areas,
drinking water
Trace Elements

Overview in thyroxin synthesis


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Trace Elements
Disorders of Iodide metabolism
• Hyperthyroidism
– due to excessive thyroid hormone secretion
• Hypothyroidism
– due to deficient thyroid hormone secretion

Hypothyriodism

● Slow metabolism ( low BMR)


● Mental dullness
Children Cretinism
● Physical slowness Adult Myxoedema
● Weight gain Goitres
● Hypercholesterolemia
Trace Elements

Clinical Features of Hypothyroidism

Puffy Eyes
Tiredness
Forgetfulness/Slower Thinking Enlarged Thyroid (Goiter)
Moodiness/ Irritability Hoarseness/
Deepening of Voice
Depression
Persistent Dry or Sore Throat
Inability to Concentrate
Difficulty Swallowing
Thinning Hair/Hair Loss
Loss of Body Hair Slower Heartbeat

Dry, Patchy Skin Menstrual Irregularities/


Heavy Period
Weight Gain Infertility
Cold Intolerance
Elevated Cholesterol Constipation
Muscle Weakness/
Family History of Thyroid Disease
Cramps
or Diabetes
Trace Elements

Primary Hypothyriodism

● Due to thyroid disease


Causes
◦ Autoimmune destruction of thyroid
◦ Inflammatory disease of the thyroid gland
◦ Over treatment for hypethyriodism
◦ Goitrogens : Nitrate (No 3-), Perchlorate (Clo4-), Thiocyanate (SCN -)
◦ Genetic desfuntion of enzymes in thyroid hormone synthesis
• Environment factors
• Endemic Goitre
• > 10-20% of population affected in SL
Trace Elements

Endemic goitres

● Inadequate iodide in the diet


◦ Common in wet zone in SL due to
leaching of soil iodine by rain
◦ Drinking water lacks sufficient iodine to
met the requirement
● Goitrogens (manioc, cabbage,
mustard)

⚫ Drugs -thiourea
⚫ Genetic Goitres
⚫ Excessive iodide

● Salt iodization – prevent from goitres


Thyroid hormone synthesis

TSH secretion

Over stimulation of thyroid cells

Enlargement of the gland

Goitres

Secondary Hypothyroidism
Decrease TSH in blood due to pituitary disease
Signs and Symptoms of Hyperthyroidism

Hoarseness/
Nervousness/Tremor
Deepening of Voice

Persistent Dry or Sore Throat


Mental Disturbances/ Irritability
Difficulty Swallowing
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/ Palpitations/

Vision Changes Tachycardia

Enlarged Thyroid (Goiter) Impaired Fertility

Weight Loss or Gain


Menstrual Irregularities/
Light Period Heat Intolerance
Increased Sweating
Frequent Bowel Movements
Sudden Paralysis
Warm, Moist Palms

Family History of
First-Trimester Miscarriage/
Thyroid Disease
Excessive Vomiting in Pregnancy
or Diabetes
Trace Elements
Zinc (Zn)
Biological Significances
• Essential for normal growth and development of animals.
Formation of zinc fingers in gene regulatory protein
(transcription factors)

• Components of many enzymes


e.g. Glutamate dehydrogenase, Alkaline phosphatase,
Thymidine kinase

• Important in Vitamin a metabolism and mobilization of


vitamin A from liver.
• Helps pancreatic β - cells to store and release insulin as
required.
• Wound healing.
Trace Elements

• Helps to maintain integrity of membranes

• Antioxidant activity

• Boost immune system

• Collagen synthesis

• Normal progress of gestation and foetal


development
Trace Elements

Daily Requirement of Zinc


● Adults usually about 15 mg /day
● Tolerable upper limit - 40 mg/day
● An increased requirement in pregnancy and
lactation, in infants and children

Food Sources
• High bioavailable
Meat, Fish Poultry, Liver
Brest milk
• Less bioavailable
Legumes and cereals
Trace Elements

Absorption and storage of Zinc

• Absorption
– Passive diffusion in distal duodenum
– Active uptake in distal ileal mucosa.
• Storage
Highest amount found in prostate gland,
spermatozoa, parts of the eye, muscles, bone
and hair.
Trace Elements

Zinc Deficiency

Primary causes
1. Inadequate intake
2. Low bioavailability( Phytate, high fiber,
calcium)
3. Iron:Zinc > 3:1
4. Inherited defects
Secondary causes
5. Malabsorption
6. Prolonged total parental nutrition
7. Sickle cell anemia
8. Hypercatabolic state burns, injuries
Trace Elements

Zinc deficiency Diseases/Symptoms

• Growth failures
• Hypogonadism and sexual infantilism in teenagers
• Poor taste sensitivity (hypogeusia)
• Persistent unpleasant taste
• Hepatospleenomegaly
• Delayed wound healing
• Anaemia
• Dermatitis and diarrhea
• Susceptibility to cold and other infections
Trace Elements
Copper (Cu)
Functions of Copper
• Aids in the oxidation of serum Fe 2+ to Fe 3+

(ceruloplasmin)

• Helping to mobilize Fe3+ from its stores

• Component of electron carriers


e.g. cofactor of cytochrome oxidase
• Participates in protein cross linking

• Inhibition of free radical generation


e.g. catalase, superoxide dismutase
• Component of many enzymes
e.g. monoamine oxidase, ascorbate oxidase, tyrosinase,
• Maintain myelin sheath integrity
Trace Elements
Daily requirement
About 900 μg/day for an adult
Tolerable upper limit – 10,000μg/day
Food Sources
Richest sources are nuts like cocoa, organ meat: liver,
kidney and dried legumes, shell fish
Cow’s milk is poor in copper.
Absorption and storage
• Mainly in stomach and proximal intestine.
• 90% of absorbed dietary Cu is taken up by liver where it is
incorporated into ceruloplasmin or stored.
• 93% serum Cu as ceruloplasmin, the remainder is bound to
albumin.
• Intracellular Cu as metallothionine.
Trace Elements

Copper Deficiency Symptoms

• Decrease energy production


• Decrease heat production
• Decrease crosslink in collagen and elastin
• Increase free radical toxicity
• Cerebral degeneration
• Anaemia
Trace Elements

Menkes syndrome
Rare, X-linked genetic disorder due to failure in
copper absorption
Low concentration of Cu in plasma and liver
• Mental retardation
• Failure to keratinize hair – kinky hair
• Hypothermia
• skeletal changes
• Aortic rupture due to
degenerative changes in aorticelastica.

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Trace Elements
Copper Toxicity
• > 10-12 mg Cu intake /day
• Copper miners, Cooking in copper pots, Genetic reasons

Acute Poisoning
Nausea, vomiting, abdominal pain, muscle pain

Wilson's disease
• Deficient synthesis of ceruloplasmin in liver
• Excess Cu accumulate in soft tissues
• Liver- cirrhosis
• Brain – cerebral disturbances
• RBC – haemolysis
• Kidney – abnormal function
• Eye corneal degeneration (Kayser Fisher ring)
• Blue-green diarrhea stools and saliva
Trace Elements
Chromium (Cr 3+)
Functions of Chromium
● Component of the glucose tolerance factor (GTF)
● Fetus depend entirely on GTF for Cr as it can cross
placenta only in this form.

Daily Requirement and sources


● 35 µg/day chromium
● Yeast, liver, beef, nuts, wholegrain,
cheese.
● Low in milk, fish, egg, fruits and
vegetables.
Trace Elements

Selenium (Se)

Functions of selenium
• Antioxidant (constituents of glutathione
peroxidase and selenoprotein)
• Reduces the requirement of Vitamin E
• Antibody production
• Protection of immune system
• Maintain tissue elasticity
• Healthy function f heart and pancreas
Trace Elements
Food sources
Vegetables, garlic, onion, sea foods
Daily requirement
60µg/day
Tolerable upper limit - 4000 mg/day
Selenium toxicity
● Due to occupational exposure in the electronics,
glass and paint industries.
◦ Garlicky breath
◦ Loss of teeth
◦ Loss of hair
◦ Painful; swellings of fingers
◦ Fatigue, Nausea, vomiting
Selenium Deficiency Disorders

1.Cardiovascular disorders- (keshan disease)


• Affect children and young woman
• Acute and chronic cardiac enlargement,
arrhythmia and E.C.G. changes. Thrombosis
2. Rheumatiod artheritis – (Kaschin-beck disease)
Osteoarthropathy of hands and fingers,
elbows knees and ankle in children and
adolescents.
3. Hypothyroid cretinism
4. Fibrocystic breast
5. Risk of Cancer
Trace Elements
Fluoride (F-)
Functions of Fluoride
• Development of bones and teeth.
• Decrease the incidence of osteoporosis
adults, especially in women after
menopause.
• Protective effect against the development of
dental caries, especially in infancy and
childhood.

Deficiency Disorders
● Osteoporosis
● Dental caries
Trace Elements

Excessive intake of Fluoride

> 1.5 mg/day

• Mottled enamel.
• Dull, chalky patches distributed irregularly over
the surfaces
• Enamel is Pitted and corroded, and
occasionally stained yellow to dark brown.
• Bone changes (e.g. increased density or
“sclerosis” of bone)
Trace Elements

Requirements

3 mg of fluoride /day

Sources
Chief source is drinking
water
Fluorine incorporated
Toothpaste
Sea fish and
Tea
THANK YOU

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