Transcript Minerals

Minerals
Minerals
• minerals are elements of the periodic
table
• more than 25 have been isolated
• 21 elements have been shown to be
essential (excluding C,H, and O)
• minerals make up about 4 to 5% of body
weight (for a 70 kg individual: 2.8 kg)
• many minerals are found in ionic form
(others as ligands or covalent
compounds)
Minerals
• Two categories:
• macrominerals > 0.005%
• microminerals < 0.005%
• macrominerals are essential at levels of
100mg or more per day for human adults
• microminerals are often referred to as
trace elements
Macrominerals
Ca
P
S
K
Cl
Na
Mg
calcium
phosphorus
sulfur
potassium
chloride
sodium
magnesium
1200 grams
860 grams
300 grams
180 grams
74 grams
64 grams
25 grams
Microminerals
F
Zn
Cu
I
Cr
Co
Si
fluorine
zinc
copper
iodine
chromium
cobalt
silicon
2.6 V
2.0 Sn
0.1 Se
0.025 Mn
0.006 Ni
0.0015Mo
0.024
vanadium 0.018
tin
0.017
selenium 0.013
manganese 0.012
nickel
0.010
molybdenum 0.009
Other microminerals found in
humans
Sr (strontium)
Br (bromine)
Au (gold)
Ag (silver)
Al (aluminum)
Bi (bismuth)
As (arsenic)
B (boron)
the function of these minerals has not been
established as of to date
Scientific development which have
contributed to trace element knowledge
• design of highly purified and specially
constituted diets
• advances in analytical measurements
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colorimetruy
fluorimetry
flame photometry
neutron activation analysis
atomic absoption spectroscopy
microwave excitation emission spectroscopy
• isolation and study of metalloenzymes
Functions of minerals
• provide a suitable medium for cellular
activity
– permeability of membranes
– irritability of muscles and nerve cells
• play a primary role in osmotic
phenomenon
• involved in acid base-balance
• confer rigidity and hardness to certain
tissues (bones and teeth)
• become part of specialized compounds
Metalloenzymes
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metal is firmly bound
metal to protein ratio is constant
metal to enzyme activity ratio is constant
metal is unique
no enzyme activity without metal
Metalloenzymes
Examples of metalloenzymes:
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superoxide dismutase (Zn and Cu)
carboxypeptidase A (Zn)
carbonic anhydrase (Zn)
cytochrome oxidase (Fe and Cu)
xanthine oxidase (Co and Fe)
Metal-activated enzymes
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metal is reversibly bound
metal to protein ratio is variable
metal to enzyme activity ratio is variable
metal is not necessarily unique
enzyme activity may exit without metal
Metal-activated ezymes
• Examples of metal-activated enzymes
– creatine kinase (Mg, Mn, Ca or Co)
– glycogen phosphorylase kinase (Ca)
– salivary and pancreatic alpha-amylases (Ca)
The electrolytes
• There are 3 major electrolytes:
– sodium
– potassium
– chloride
Sodium (Na)
• Sodium is the principal cation in
extracellular fluids
• functions include:
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osmotic equilibrium
acid-base balance
carbon dioxide transport
cell membrane permeability
muscle irritability
Sodium (Na)
• food sources: table salt, salty foods
(potato chips, pretzels, etc.), baking soda,
milk
• absorption and metabolism:
– readily absorbed
– excreted in the urine and sweat
– aldosterone increases reabsorption in remal
tubules
Sodium (Na)
• RDA for adults: 1.1 to 3.3 gm/day
• sodium deficiency:
– dehydration
– acidosis
– tissue atrophy
• sodium excess:
– edema (hypertonic expansion )
– hypertension
Sodium (Na)
• Sodium supplements:
– usually used to replace sodium and chloride
lost through perspiration during high heat
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Thermotabs
Slo-salt
Heatrol
Lytren solution
Pedialyte solution
Gatorade and other sports drinks
Potassium (K)
• Potassium is the principal cation in
intracellular fluid
• functions:
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buffer constituent
acid-base balance
water balance
membrane transport
neuromuscular irritability
Potassium
• Food sources: vegetables, fruit (bananas),
whole grains, meat, milk
• absorption and metabolism:
– readily absorbed (more so than sodium)
– intracellular
– secreted by kidney (also in sweat)
• RDA for adults: 1.5 - 4.5 gm/day
Potassium
• deficiency (hypokalemia)
– causes:
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increased renal excretion (diuretics)
primary aldosteronism
severe vomiting and diarrhea
cutaneous losses via perspiration
– symptoms:
• profound weakness of skeletal muscles (paralysis
and impaired respiration
• weakness of smooth muscles
• cardiac anomalies: AV block, cardiac arrest
Potassium
• excess (hyperkalemia)
– causes:
• sudden increased intake
• severe tissue trauma and burns
• acute and chronic acidosis
– symptoms:
• weakness and paralysis
• cardiac anomalies (impaired conduction,
fibrillations, cardiac arrest)
Potassium supplements
• Oral products:
– tablets: potassium chloride, potassium
gluconate, Slow-K
– effervescent tablets: K-Lyte, K-Lor,
Kaochlor
– parenteral products: usually administered
by slow IV infusion (KCl and K acetate)
Treatment of hyperkalemia
• reverse cardiotoxic effects:
– calcium gluconate IV
• increase potassium uptake by cells:
– dextrose (IV)
– insulin (IV)
– sodium bicarbonate (IV)
• remove excess potassium from the body:
– sodium polystyrene sulfonate (Kayexalate)
Chloride (Cl)
• an essential anion
• closely connected with sodium in foods,
body tissues and fluids and excretions
• readily absorbed along with sodium
• excreted mainly in the kidneys (~ 2% in
feces and ~ 4-5% in perspiration )
• important for osmotic balance, acid-base
balance and in the formation of gastric
HCl
Chloride (Cl)
• Deficiency of chloride:
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hypochloremic alkalosis
hypovolemia
pernicious vomiting
psychomotor disturbances
Calcium (Ca)
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the most abundant of the minerals
the 5th most abundant element in the body
needed by all cells
found in largest amounts in bones (90%)
found in bone as hydroxyapatite
Ca10(PO4)6(OH)2
• contaminated with sodium, potassium,
magnesium, carbonate and fluoride
Calcium (Ca)
• controlled by parathyroid hormone
(PTH), calcitonin and vitamin D
• maintained at a concentration of 5
mEq/L in plasma
• about 1/2 is in the ionized form in serum
• the other 1/2 is bound to protein (calcium
citrate complex)
Calcium (Ca)
• function of calcium:
– structural unit of bones and teeth
– contraction and relaxation of muscles
– stabilizes nervous tissue
• low calcium --- irritable nerves --- tetany
• high calcium --- depresses the nervous irritability
– required for blood clotting
– activates various enzymes (glycogen
phosphorylase kinase, salivary and
pancreatic amylase)
Calcium (Ca)
• Calcium absorption:
– variable due to insoluble salts:
• phosphate
• carbonate
• oxalate
• phytate
• sulfate
– also forms calcium soaps with fatty acids
• absorption is enhanced by:
• acid pH
• vitamin D
• lactose
• lysine and glycine
Calcium (Ca)
• Excretion:
– urine and feces
– enhanced by lack of vitamin D and ingestion
of large quantities of proteins (acid urine)
• RDA
– adult: 800 mg/day
– pregnacy and lactation: 1200 mg/day
Calcium supplements
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calcium gluconate:
calcium lactate
calcium carbonate
dibasic calcium phosphate
calcium glucobionate
calcium chloride
calcium levulinate
9%
13%
40%
30%
6%
27.2%
13%
Phosphorus
• required in many phases of metabolism
• food sources:
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phosphoproteins
nucleoproteins
nucleolipids
glycerophosphates
inorganic phosphates (Na and Ca)
• foods rich in calcium are also richest in
phosphorus (milk, cheese, eggs, beans,
fish)
Phosphorus
• Phosphorus is the second most abundant
mineral in the body (22% of total mineral
content; 80% is structural – insoluble apatite in
bone and teeth)
• 20% is very active metabolically:
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High energy phosphate compounds
Nucleic acids
Phospholipids
Phosphoproteins
Coenzymes (vitamins)
Phosphorus
• RDA for phosphorus is established on the basis
of a 1:1 relationship with calcium
– Adults: 800 mg/day
– Pregnancy and lactation: 1200 mg/day
• Phosphorus deficiency (hypophosphatemia)
• Not common
• May be associated with total parenteral nutrition (TPN)
without sufficient phosphates; give either sodium or
potassium phosphate
Magnesium (Mg)
• second most plentiful cation in
intracellular fluids
• ~50% of total amount in bone
• ~45% in muscle and nervous tissue
• ~ 5% in extracellular fluids
• blood plasma magnesium : ~ 2 mEq/L
Magnesium (Mg)
• Functions:
a. enzyme systems
– cofactor of all enzymes involved in
phosphate transfer reactions that use ATP
and other nucleotide triphosphates
– phosphatases
– pyrophosphatases
Magnesium (Mg)
b. CNS
– hypomagnesemia ---- cns irritability,
disorientation, psychotic behavior,
convulsions
c. neuromuscular system:
– magnesium has a direct depressant effect on
skeletal muscle
– magnesium also causes a decrease in Ach
release at motor end plate (used in treatment
of eclamptic seizures)
Magnesium
• Abnormally low concentrations of Mg in
the extracellular fluid ---- increased Ach
release ---- increased muscle excitability
(tetany)
• food sources: all green plants
(chlorophyll); meats
• RDA: 350 mg/day
– pregnancy and lactation: 450 mg
Zinc
• Biological roles
– Involved in many enzymes (over 20 metalloenzymes)
• Carbonic anhydrase
• Carboxypeptidase A
– Four types of proteases
» Serine
» Cysteine
» Aspartic acid
» Zinc
• ACE (angiotensin I convering enzyme)
• RNA and DNA polymerases
Zinc
• zinc absorption appears to be dependent
on a transport protein, metallothionein
• deficiencies include poor growth, delayed
wound healing, impairment of sexual
development and decreased taste acuity
• zinc is present in gustin, a salivary polypeptide
that is necessary for the development of taste
buds
Zinc
• severe zinc deficiency is seen primarily in
alcoholics (especially if they have developed
cirrhosis), patients with chronic renal disease
or severe malabsorption diseases
• occasionally seen in patients on long term total
parenteral nutrition (TPN) –patient develop a
dermatitis
• zinc is occasionally used therapeutically to
promote wound healing and may be of some
use in treating gastric ulcers
Zinc supplements
Iron (Fe)
• 2 types of body iron
– heme iron
• hemoglobin, myoglobin, catalases, peroxidases,
cytochromes (a, b and c – involved in electron transport),
cytochrome P450 (involved in drug metabolism)
– non-heme iron
• ferritin, hemosiderin, hemofuscin, transferrin,
ferroflavoproteins, aromatic amino acid hydroxylases
• food iron is also classified as heme and nonheme
Food iron
heme iron
– meats
– poultry
– fish
20-23% of heme-iron is
absorbable
non-heme iron
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vegetables
fruits
legumes
nuts
breads and cereals
only ~ 3% on non heme
iron is absorbed
Iron absorption
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occurs in upper part of small intestine
about 10% of food iron is absorbed
requires gastric HCl (releases ionic iron)
also requires copper
ferrous is better absorbed than ferric
form
• Fe++ forms chelates with ascobic acid,
certain sugars and amino acid
Iron distribution and storage
• carried in blood stream via transferrin (a
b globulin)
• stored in 2 forms:
• ferritin (a water soluble complex consisting of a
core of ferric hydroxide and a protein shell
(apoferritin)
• hemosiderin (a particulate substance consisting
of aggregates of ferric core crystals)
• stored in liver, spleen, bone marrow,
intestinal mucosal cells and plasma
FOOD IRON
gastric HCl, ascorbic acid
Fe++
unabsorbed Fe
(fecal excretion)
mucosal cell
(upper small
intestine)
Fe+++
APOFERRITIN
FERRITIN
intestinal
secretion
1-2 mg/day
apotransferin
plasma
Fe+++ - transferrin
Fe++ - hemoproteins
(hemoglobin, myoglobin
Fe+++ - ferritin
Fe+++ - hemosiderin
bone marrow
muscle
liver
Iron elimination
• there is no mechanism for excretion of iron
• iron is normally lost by exfoliation of
intestinal mucosal cells into the stools
• trace amounts are lost in bile, urine and
sweat (no more than 1 mg per day)
• bleeding (vaginal, intestinal) is a more
serious mechanism of elimination
IRON DEFICIENCY
Initial symptoms are vague and ill-defined
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easy fatigability
lack of appetite
headache
dizziness
palpitations
then: hypochromic-microcytic anemia
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microcytosis (small RBCs)
hypochromia (poor fill of hemoglobin)
poikilocytosis (bizarre shapes)
anisocytosis (variable sizes)
IRON DEFICIENCY
Causes:
– excessive blood loss (parasitic, accidental,
menstrual): is most common cause
– rapid growth in children with limited intake of iron
– malabsorption
• gastric resection
• sprue
– increased metabolic requirement
• pregnancy, lactation or neoplasia
Diagnosis of iron deficiency
• hematology (microcytic hypochromic cells)
• low serum iron
• low serum ferritin( indicates low body stores)
• in some conditions (inflammation, hepatitis)
ferritin may be high
• low hemosiderin
• high total iron binding capacity (TIBC)
Iron absorption
• average diet contains 10 - 15 mg of iron perday
• a normal person absorbs 5 -10% of this iron or
0.5 - 1.0 mg daily
• iron absorption increases in response to low
iron stores
• menstruating women: 1 - 2 mg per day
• pregnant women: 3 - 4 mg per day
• absorption is via active process
Different types of iron
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Ferrous sulfate
Exsiccated ferrous sulfate
ferrous gluconate
ferrous fumarate
ferrocholinate
polysaccharide-iron complex
iron dextran (Imferon)
20%
11.6%
33%
12%
Treatment of iron deficiency
• give 200 - 400 mg of iron per day
• up to 25% of the iron preparation may be
absorbed
• 50 - 100 mg of iron may be utilized in case of
deficiency
• give on an empty stomach
• enteric coated iron tablet should not be used
since we want absorption to occur in the
stomach and proximal duodenum
Treatment of iron deficiency
• parenteral iron is used in patients who
have had bowel resections or in cases of
inflammatory bowel disease
– normally given IM (painful) Z-track
minimizes tatoo
• oral iron causes black stools,
constipation, cramping
• do not administer with antacids or metal
chelators (tetracyclines)
Acute iron toxicity
common in small children ingesting large
doses of soluble iron compounds
toxicity is usually divided into 4 phases:
1. 30 - 60 min. following ingestion
• abdominal pain
• nausea and vomiting
• signs of acidosis and cardiovascular collapse may
be seen
Acute iron toxicity
2. Period of improvement - last about 8 to
16 hours
3. Period of progressive cardiovascular
collapse (about 24 hrs after ingestion)
• convulsions
• coma
• high mortality
4. Gastrointestinal obstruction from
scarring of stomach and small intestine
Deferoxamine mesylate (DFOM)
O
H2N
(CH2)5 C
N
OH
O
C
(CH2)2 N
H
(CH2)5 OH
N
N
H
C
O
O
(CH2)5 C
N
C O
(CH2)2
OH
A chelating agent which reacts with ferric ion to form a
1:1 chelate known as ferrioxamine
Marketed as Desferal Injection (Ciba)
Produced by Streptomyces pilosus
CH3
Chronic iron toxicity
• causes
• hereditary hemochromatosis
• hemosiderosis
• symptoms
• cirrhosis: iron deposition in the liver
• diabetes: iron deposit in the pancreas (damage to
beta cells)
• skin pigmentation
• cardiac failure
• treatment: phlebotomy ( 1 unit of blood removes
about 250 mg of iron
Copper
• important trace mineral
• element 29 on the periodic table
• component of several enzymes:
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ceruloplasmin (an oxidase)
tyrosinase (production of melanin)
amine oxidase (metabolism of catecholamines)
cytochrome C oxidase
dopamine beta hydroxylase
copper/zinc superoxide dismutase
Copper (Cu)
• Deficiency
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decreased iron absorption
neutropenia and leukopenia
bone demineralization
failure of erythropoiesis
• sources
• liver, shellfish, whole grains, cherries, legumes,
nuts
Fluorine
• Considered essential because of its beneficial
effect on tooth enamel
• Benefits include: less dental caries, stronger
bones, reduction in osteoporosis and
calcification of the aorta
• In large quantities it is deleterious to teeth;
dental fluorosis: pitting, chalky, dull white
patches and mottling of teeth
• 1 to 2 parts per million is adequate for drinking
water
Iodine
• iodine is necessary for the formation of thyroid
hormones (T-4 and T-3)
• deficiency of iodine is manifested by a goiter
(enlargement of the thyroid gland)
• salt water fish and seaweeds are a good source
of iodine
• to prevent the development of endemic goiter,
tablet salt has been spiked with sodium iodide
Fluorine
• Main sources include drinking water and
plants (spinach, lettuce, onions)
• Average daily intake: 1.5 – 4.0 mg/day
• Fluoride supplementation is available in
both oral and topical forms:
• Oral: mainly sodium fluoride (Pediaflor Drops)
• Topical: either sodium or stannous fluoride
(Fluorigard, Karigel, Fluoral)
Silicon
• essentiality has been established in chicks
and rats, but not humans
• appears to play an important role in the
development and maintenance of
cartilage (chondroitin sulfate, hyaluronic
acid, keratin sulfate)
• may have a protective role in
cardiovascular diseases (atherosclerosis)
• found in unrefined grains and beer
Manganese
• Maganese is an activator of several different
enzymes:
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Phosphoglucomutase
Isocitric dehydrogenase
Cholinesterase
Intestinal peptidase
Carboxylases
ATPases
• However, magnesium and cobalt can replace
Mn in several enzymes
Manganese
• Essential for sulfomucopolysaccharide
biosynthesis
• Deficiency leads to:
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Weight loss
Transient dermatitis
Nausea and vomiting
Changes in hair color
• Sources: blueberries, wheat bran, beet greens,
lettuce, legumes, fruit
• RDA: 2.5 – 5.0 mg
Chromium
• Cr III may act as a cofactor for insulin, enhancing
glucose utilization
• deficiency leads to impaired glucose tolerance (glucose
tolerance factor)
• sources: corn oil, whole-grain cereals, clams, drinking
water (variable)
• forms a coordination complex with micotinic acid and
the amino acids glycine, glutamate and cysteine
• chromium may have a role in type 2 diabetes
• RDA: 0.05 – 0.2 mg
• frequently available in pharmacies as chromium
picolinate
Selenium
• prevents:
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muscular dystrophy in lambs, calves and chicks
liver necrosis in rats and pigs
exudative diathesis in chicks and turkeys
multiple necrotic degeneration of heart, liver, muscle and
kidneys in mice
• appears to function in the metalloenzyme
glutathione peroxidase, which destroys
peroxides in the cytosol
• no deficiencies have been seen in humans
• has antioxidant activity (may have relationship
with vitamin E - sparing action)
Tin
• produces accelerated growth in deficient
rats
• tin is similar to carbon in its tendency to
form covalent bonds
• may have a role with heme-containing
enzymes:heme oxygenase and
cytochrome P-450
• largest quantities are found in kidneys
and skin
• human intake: ~ 1.5 - 3.5mg/day
Cobalt
• essentiality exists in some animals for
ionic cobalt (sheep and cattle)
• in rats administration of cobalt produces
a polycythemia
• cobalt in necessary in humans in the form
of vitamin B12
• animals and plants cannot synthesize B12
• daily intake: 0.3 mg
Vanadium
• essentiality established in rats and chicks
• human daily intake has been estimated at
2 mg
• plays a role in lipid metabolism (deficient
chicks have a high plasma cholesterol
and triglyceride levels)
• may also function as an oxidationreduction catalyst
Molybdenum
• Widely found in commonly used foods
(cereals, vegetables
• Mo is part of flavoproteins, xanthine
oxidase, aldehyde oxidase
Sulfur
• Most sulfur in the diet comes in from protein
sources containing sulfur amino acids such as
cysteine, cystine and methionine
• Some enters as inorganic sulfur (sulfate,
sulfide, chondroitin sulfate and certain other
sulfate esters)
• Sulfur is also present in thiamine, biotin,
sulfolipids, conjugated bile acids and coenzyme
A