Water & Mineral
metabolism
Mr. Kuldeep Bansod
Department of Pharmacy,
Government Polytechnic, Jalgaon
Maharashtra- 425001
WATER
Most abundant
compound in the body
(65-95% of body
weight)
Special properties-
polarity
H bonding
It is a negative water balance leading to a decrease in
water content of the body.
This occurs when the output of water is more than intake.
Signs and Symptoms of Dehydration
Mild to Moderate Dehydration Severe Dehydration
Dry, sticky mouth Extreme thirst
Sleepiness or tiredness Irritability and confusion
Dry skin Sunken eyes
Dry skin that doesn't bounce
Headache
back when you pinch it
Constipation Low blood pressure
Dizziness or lightheadedness Rapid heartbeat
Few or no tears when crying Rapid breathing
Minimal urine No tears when crying
Dry, cool skin3 Fever
Little or no urination, and any
Muscle cramps urine color that is darker than
usual
In serious cases, delirium or
unconsciousness
Mineral
metabolism
Functions of Minerals
• Some participate with enzymes in
metabolic processes (cofactors, e.g. Mg,
Mn, Cu, Zn, K)
• Some have structural functions (Ca, P in
bone; S in keratin)
• Acid-base and water balance (Na, K, Cl)
• Nerve & muscle function (Ca, Na, K)
• Unique functions: hemoglobin (Fe),
Vitamin B12 (Co), thyroxine (I).
Classification
• Macro or Major • Micro or Trace minerals
minerals (body needs relatively
– Sodium (Na), less)
potassium (K), – Manganese(Mg),
magnesium (Mg), iron(Fe), cobalt(Co),
calcium (Ca), chromium(Cr),
phosphorus (P), sulfur molybdenum(Mo),
copper(Cu), zinc(Zn),
(S), chloride (Cl)
fluoride(F), iodine(I),
• Present in body tissues selenium(Se)
at concentrations >50 • Present in body tissues
mg/kg at concentrations <50
• requirement of these is mg/kg
>100 mg/d • requirement of these is ﹤
100 mg/d
Nutritionally Important Minerals
Macro Trace
Element g/kg Element mg/kg
Ca 15 Fe 20-50
P 10 Zn 10-50
K 2 Cu 1-5
Na 1.6 Mo 1-4
Cl 1.1 Se 1-2
S 1.5 I 0.3-0.6
Mg 0.4 Mn 0.2-0.5
Co 0.02-0.1
Minerals in Foods
• Found in all food groups.
• More reliably found in animal
products.
• Often other substances in
Oxalate foods decrease absorption
(bioavailability) of minerals
– Oxalate, found in spinach,
prevents absorption of most
calcium in spinach.
– Phytate, form of phosphorous
in most plants makes it poorly
available
Phytate
Factors Affecting Requirements
• Physiological state/level of production
• Interactions with other minerals
Deficiencies and Excesses
• Most minerals have an optimal range
– Below leads to deficiency symptoms
– Above leads to toxicity symptoms
• Mineral content of soils dictates
mineral status of plants (i.e., feeds)
• May take many months to develop
Calcium (Ca)
• Most abundant mineral
in animal tissues
– 99% Ca in skeleton
– 1% Present in:
• Blood & other tissues
• Lots of functions
– Bone structure
– Nerve function
– Blood clotting
– Muscle contraction
– Cellular metabolism
Dietary requirements
• Dietary requirements:
– Adult : 800 mg/day;
– Women during pregnancy, lactation and post-
menopause: 1.5 g/day;
– Children (1-18 yrs): 0.8-1.2 g/ day;
– Infants: (< 1 year): 300-500 mg /day
• Food Sources:
– Best sources: milk and milk product;
– Good sources: beans, leafy vegetables, fish,
cabbage, egg yolk.
• Absorption of calcium:
– in small intestine (duodenum), first half
jejunum against electrical and concentration
gradient, by an energy dependent active
process, which influenced by several factors.
Simple diffusion
Mechanism
An active transport involving Ca pump
Factor promoting Ca absorption
1. Vit.D induce the synthesis of Ca binding protein in
the intestinal epithelial cells and promotes Ca
absorption.
2. Parathyroid hormone (PTH) enhances Ca absorption
through the increased synthesis of calcitriol.
3. Acidity (low pH) is more favorable for Ca absorption.
4. Lactose promotes calcium uptake by intestinal cell.
5. Lysine and arginine facilitate Ca absorption.
Factor inhibiting Ca absorption
1. Phytates and oxalates form insoluble salts and
interfere with Ca absorption.
2. The high content of dietary phosphate results in the
formation of insoluble Ca phosphate and prevent Ca
uptake.
Dietary ratio of Ca : P ---1:1 to 2:1--- is ideal for Ca absorption.
3. The free fatty acids are react with Ca to form
insoluble Ca soaps.
4. The alkaline condition (high pH) is unfavorable for
Ca absorption.
5. High content of dietary fiber interferes with Ca
absorption.
6. Low estrogen levels (postmenopausal women)
• Plasma calcium:
normal range: 9-11 mg% (2.25-2.75 mmol/L)
Three forms of plasma calcium:
① Ionized Ca (diffusible): about 50% is ionized from which
functionally the most active.
② Complex Ca with organic acid (diffusible): about 10% is
found in association with citrate or phosphate.
③ Protein bound Ca (non-diffusible): about 40% is found
in association with albumin and globulin.
Ca
[H+] [H+]
Protein Ca anion Ca
[HCO3 ] -
Ca [HCO3 ]
-
Ca
Factors Regulating Plasma Ca Level
• Plasma Ca is regulated variable
• Three hormones involved in regulation
– Calcitriol (1,25-(OH)2 VitD3, or 1,25 DHCC)
• from kidney
– Parathyroid hormone (PTH)
• from parathyroid gland
– Calcitonin(CT)
• from thyroid gland
• Vitamin D3 and PTH : increase plasma Ca↑
• Calcitonin : decrease plasma Ca↓
Regulation of Calcium Homeostasis
Excretion of Ca
• Partly through the kidney.
• Mostly through the intestine.
• Notice: excretion of Ca into the feces is
a continuous process and this is
increased in vitamin D deficiency.
Calcium Deficiencies
-Rickets
weakness and deformity of the bones that occurs from
vitamin D deficiency or dietary deficiency of Ca and P
in a growing person or animal.
Calcium Deficiencies
-Osteoporosis
progressive loss of bone density, thinning of bone tissue
and increased vulnerability to fractures in the elderly
people of both sexes.
Calcium and Osteoporosis
• Bone growth is greatest during “linear growth”
– Peaks out at around age 30
• Around age 40,
bone breakdown
exceeds
formation.
• By age 65, some
women have lost
50% of bone
mass.
Prevention is the Key
• Maintain adequate
calcium and vitamin D
intake —many
recommend supplements?
• Perform weight-bearing
exercise.
• Take estrogen
supplements to
postmenopausal?
Calcium Toxicity
• Deposition in soft tissue
• Impaired kidney function
• Interference of other nutrient
absorption
– Iron & zinc
Phosphorous (P)
• 80% of P occurs in combination with Ca in
the bone and teeth.
• About 10% is found in muscles and blood in
association with proteins, carbohydrate and
lipids.
• The remaining 10% is widely distributed in
various chemical compounds.
Functions of Phosphorus
• Essential for the development of bones and
teeth
• Phospholipids, Phosphoproteins
• Component of:
– DNA & RNA
– ATP, NAD+, NADP+
• Energy metabolism: ATP, GTP
• Maintenance of blood pH: phosphate buffer
system
Dietary requirements
• The recommended dietary allowance (RDA) of
phosphate is based on the intake of calcium.
– For adult, the ratio of Ca:P of 1:1 is
recommended (800mg/day);
– For infant, however, the ratio is around 2:1,
which is ratio found in human milk.
• Sources:
– milk, cereals, leafy vegetable, meat, eggs.
Absorption and Excretion
Absorption:
Phosphate absorption occur from jejunum
1. Calcitriol promotes phosphate uptake along with
calcium.
2. absorption of P and Ca is optimum when the dietary
Ca:P is 1:2-2:1.
3. acidity favors while phytate decreases phosphate
uptake by intestinal cells.
Excretion:
About 500 mg phosphate is excreted in urine per day.
The reabsorption of phosphate by renal tubules is inhibited
by PTH.
Serum phosphate
blood: 40 mg/dl serum: 3-4 mg/dl
※ RBC and WBC have very high content of
phosphate.
※
※ The serum P may exist as free ions (40%) or
in a complex form (50%) with cation as Ca2+,
Mg2+, Na+, K+. About 10% is bound proteins.
• Importance of Ca:P ratio
– The ratio of plasma Ca:P is important for
calcification of bones.
• The product of Ca×P (in mg/dl) in child is
around 50 and in adults around 40. This
product is less than 30 in rickets.
• Phosphorus Deficiency
– Rickets, osteomalacia, osteoporosis
Factors Regulating Ca and P
hormone 1,25 DHCC PTH CT
Ca absorption in intestine ↑↑ ↑ ↓
osteolysis ↑ ↑↑ ↓
osteogenesis ↑ ↓ ↑
Ca excretion from ↑ ↓ ↑
kidney
P excretion from kidney ↓ ↑ ↑
Blood calcium ↑ ↑ ↓
Blood phosphorus ↑ ↓ ↓
Sodium (Na)
• Principal cat ion of
ECF
• Lots of functions
– Acid base balance
– Nerve function
– Osmotic function
– Permeability
Trace Elements (minerals)
• Need small amounts of these.
• Found in plants and animals.
• Content in plant foods depends on soil
content (where plant was grown).
• They are difficult to quantify
biochemically.
• Bioavailability often influenced by other
dietary factors (especially other minerals)
Iron
• The total content of iron in an
adult body is 3-5 g.
1. About 70%: in the erythrocytes of
blood as a constituent of Hb.
2. At least 5%: in Mb of muscle.
3. Heme is the most predominant iron
containing substance: e.g. Hb, Mb,
cytochromes.
4. Non-heme iron: e.g. transferrin,
ferritin.
Functions
• O2 and CO2 transport via
hemoglobin
– Thus, necessary for ATP
production!
• Essential component of many
enzymes
• Immune function
• Brain function
– Iron deficiency/toxicity
thought to slow mental
development in kids.
Dietary requirements
• Dietary requirements:
– Adult man: 10 mg/day
– Menstruating woman: 18
mg/day
– Pregnant and lactating woman:
40 mg/dl
• Sources:
– Rich source: organ meats
(liver, heart, kidney).
– Good source: leafy
vegetables, pulses, cereals,
fish, apple, dried fruits,
molasses.
– Poor sources: milk, wheat,
Iron absorption
• Iron is mainly absorbed in the stomach and duodenum.
– mostly found in the food in ferric form (Fe3+), bound to
protein or organic acid.
– In the acid medium provided by gastric HCl, the Fe3+ is
released from food.
– Reducing substances such as ascorbate (Vitamin C) and
cystein reduces ferric form (Fe3+) to ferrous form (Fe2+).
– Iron in ferrous form (Fe2+) is soluble and readily absorbed.
• How much do we absorb?
– We absorb iron from the diet only when we need it
– In normal people, about 10% of dietary iron is usually
absorbed.
– Those with LOW stomach acid secretions absorb less.
• Iron storage
– Iron can be stored by ferritin (a protein)
or hemosiderin
• Stored in liver, bone marrow (why here?),
intestinal mucosa, and spleen
• A apoferritin molecule can combine with
4,000 atoms of iron.
Ferritin Ferritin
• Iron transport in the plasma
– The iron enters the plasma in ferrous state
(Fe2+), then oxidized to ferric form (Fe3+) by a
copper-containing protein, ceruplasmin.
– Fe3+ binds with a specific iron binding protein,
namely transferrin. Each transferrin molecule
can bind two atoms of ferric iron.
Transferrin
Basic Iron Metabolism
A general overview of
iron metabolism
Disease states
1. Iron Deficiency Anemia: The most common dietary
deficiency worldwide is iron, affecting half a billion
persons. However, this problem affects women and
children more.
a) A growing child is increasing the RBC mass and
needs additional iron.
b) Women who are menstruating require double the
amount of iron that men do, but normally the
efficiency of iron absorption from the
gastrointestinal tract can increase to meet this
demand.
c) A developing fetus draws iron from the mother,
totaling 200-300 mg at term, so extra iron is
needed in pregnancy.
2. Hemosiderosis: this is less common disorder and due
to excessive iron in the body.
– It is commonly observed in subjects receiving
repeated blood transfusions over the years, e.g.
patients of hemolytic anemia, hemophilia.
3. Hemochromatosis: this is rare disease in which iron
is directly deposited in the tissue (liver, spleen,
pancreas and skin).
– Bronzed-pigmentation of skin, cirrhosis of liver.
pancreatic fibrosis are the manifestations of this
disorder.
Potassium
1. It is major intracellular cation.
2. Distributed in body tissue and body
fluids.
3. High concentration present in nerve
cells, cells, muscles and blood.
Hypokalemia
• Decrease in serum potassium level.
• It occurs in-
– Cushing’s syndrome
– Severe Vomiting & diarrhoea
– Prolonged use of diuretics
– Familial periodic paralysis
Hyperkalemia
• Increase in serum potassium level.
• It occurs in-
– Renal failure
– Severe dehydration
– Addison’s disease
– Excessive administration of IV potassium
Chlorine
Magnesium
• Intracellular ion of all living cells and
tissues.
• Total body content is 21 gm.
• 70% present in bones in combination
with calcium & phosphorus.
Iodine
• Normal adult has 20-50 mg
• 80% of iodine present in thyroid
gland.
• Daily requirements- 100-200mcg/day.
Age groups Disorders
All ages Goiter, Hypothyroidism, radiation
susceptibility
Fetus Absorption, still birth, Congenital
abnormalities
Neonates Infant mortality, endemic cretinism
Children Subnormal mentation, delayed development
Adults Impaired mental function, poor performance
Points
• Functions of minerals
• Macro (or major) minerals and micro (or trace)
minerals
• Calcium (Ca)
– Functions, Factor promoting (or inhibiting) Ca absorption
– Three forms of plasma calcium
– Factors Regulating Plasma Ca Level: Vitamin D3, PTH and
calcitonin
– Calcium Deficiencies: Rickets, Osteoporosis
• Phosphorous (P)
– Functions, Serum phosphate, Importance of Ca:P ratio,
Factors Regulating Ca and P
• Iron
– Iron absorption, storage and transport in the plasma,
Disease states
