Mineral FROM MY LECTURE

8/12/2019 Mineral FROM MY LECTURE

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MINERALAmallia N. Setyawati

Department of [email protected]



Minerals

• A naturally occurring , homogeneous, inorganic

substance required by humans in amount of 100

mg/day or more.

• Dietary minerals support biochemical reactions byserving both functional and structural roles as well as

those serving as electrolytes.

– -functions -excretion

– -deficiency -high and low serum levels

– -toxicity

– -absorption



Mineral requirement



Functions of minerals

• provide a suitable medium for cellularactivity – 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



Mineral function:summary



Major Minerals

• Major (macro) minerals

– Ca, P, K, Mg, Na, Cl, S

– Included as % in diet

• Functions

– Structural

– Nerve

– Electrolytes

– Osmotic balance



Bioavailability, & Regulation of Major

Minerals

• Bioavailability

– Influenced by genetics, aging, nutritional status & other

food compounds

•Absorption – Small intestine & large intestine

• Regulation

– Kidneys & small intestine



Trace Minerals

• Trace (micro) minerals

– Cobalt, copper, iodine, iron, manganese,

molybdenum, selenium and zinc all required

– Chromium-no established requirement

– Included as ppm or ppb in diet

• Function

– Enzyme co-factor or component



QUIZ

1. Name macromineral

2. Increased amount intake in pregnancy

3. Absorption of mineral takes place in



Calcium

-most abundant mineral in the body

-99% of calcium is in the bones and teeth

-the remaining 1% is in the blood and ECF in cells

and soft tissues



Calcium Deficiency and Bone

Calcium supplements can helpprevent osteoporosis, which is a

condition that occurs when bone

breaks down more quickly than it is

replaced. In this illustration, the bone

above is normal, but the bone below is

more porous and therefore moresusceptible to fracture.

-if there is no reserve,calcium is drawn

from bone—leadingto deficiency

Skeletal Calcium



• Serum levels: 8.8 to 10.8 mg/dl

• **when albumin is low (malnutrition, liver dz),

calcium is decreased

• Ratio: for each gram albumin is decreased

below 4, add 0.8 to calcium



• -ionized calcium is increased in acidosis anddecreased in alkalosis (increased bicarb bindscalcium)

•

***-example: in resp alkalosis, total serum calcium isnormal, but ionized is low—always check ionizedlevel with acid/base disorders



Functions

• -building and maintaining bones and teeth

• -transport fxn of cell membranes and membranestabilizer

•

***-nerve transmission and regulation ofheartbeat—use calcium gluconate IV to treathyperkalemia (EKG—peaked T waves)

• -ionized form initiates formation of the blood clot

• -cofactor in conversion of prothrombin to thrombin



Absorption

• -***absorbed mainly in the acidic part of theduodenum

• -absorption is decreased in the lower GI tract which

is more alkaline• 20-30% of digested calcium is absorbed

• Absorption is thru 1,25 (OH)2D3 (vit D derivative)--stimulates production of calcium binding protein and

alk phos• -unabsorbed form is excreted in feces



Factors that increase calcium

absorption• -***more efficiently absorbed when the body is

deficient

• -best absorbed in acidic environment (upperduodenum)

• -HCL in stomach allows better absorption in theproximal duodenum

• -taking calcium with food increases abs

• -fat increases intestinal transit time and increasesabsorption



Factors that decrease absorption

• -***lack of vitamin D

• -oxalic acid forms insoluble complex which decreasesabsorption (rhubarb, spinach, chard, beet greens)

•

-phytic acid found in outer husks of cereal grains alsoform insoluble complex

• -alkaline medium decreases abs.(lower GI tract)

• Aging decreases absorption



Maintenance of serum level cont’d

• ***-always need to correct low Mg level

before treating a low calcium level

• -hypomagnesemia decreases tissue

responsiveness to PTH



Maintenance of serum level

• -parathormone (PTH) by the parathyroid gland andthyrocalcitonin secreted by the thyroid glandmaintain serum levels

• -***with decreased serum calcium levels, PTHincreases and causes transfer of calcium from boneto blood to increase serum levels

• -decreased levels also cause kidney to reabsorb

calcium more efficiently (might normally be excretedin the urine) and to increase intestinal absorption

• -when blood levels are increased, calcitonin acts bythe opposite mechanisms as PTH to decrease serum

levels



Causes of hypocalcemia

-***malabsorption

-small bowel bypass, short bowel

-vit D deficiency-alcoholism

-***chronic renal insufficiency

-***diuretic therapy



Causes of hypocalcemia cont’d

-hypoparathyroidism

-***hypomagnesemia

-sepsis-pseudohypoparathyroidism

-calcitonin secretion with medullary

carcinoma of the thyroid



Causes of hypocalcemia cont’d

-***associated with low serum albumin

(ionized calcium will be wnl)

-decreased end organ response to vit D

-hyperphosphatemia

-***aminoglycosides, plicamycin, loop

diuretics, foscarnet



Causes of hypercalcemia

-milk-alkali syndrome

-vit D or vit A excess

-primary hyperparathyroidism

-secondary hyperparathyroidism (renal insuff,malabsorption)

-acromegaly

-adrenal insufficiency



Causes of hypercalcemia cont’d

-***thiazide diuretic

-sarcoidosis

-paget’s disease of bone -***immobilization

-familial hypocalciuric hypercalcemia

-complications of renal transplant-iatrogenic



Causes of hypercalcemia cont’d

***Neoplastic Disease

-tumors producing PTH-related proteins(ovary, kidney, lung)

-***mets to bone

-lymphoproliferative disease includingmultiple myeloma

-secretion of prostaglandins and osteolyticfactors



Excretion

• -normal is 65-70% of ingested calcium to be

excreted in the feces and urine

• -strenuous exercise increases loss (in sweat)

• -***immobility with bed rest and space travel

increase calcium loss because of lack of bone

tension



sources



Deficiency

• 1)***bone—to be discussed in internal medicinelecture

• 2) tetany—decreased serum levels increase theirritability of nerve fibers resulting in muscle spasms,fatal laryngospasm

– ***-Chvostek’s sign: contraction of the facial m. aftertapping the facial n.

– ***-Trousseau’s sign: carpal spasm after occlusion of the

brachial a. with blood pressure cuff for 3 min

• 3) HTN—controversial

• 4) prolonged QT--arrythmias



30

Calcium



Risk Factors- By Mayo Clinic staff

Your gender.

Age. Race.

Frame size.

Eating disorders.

Low calcium intake.Excess soda consumption (Ca:P ratio). The link between osteoporosis and caffeinated sodas isn't clear, but

caffeine may interfere with calcium absorption and its diuretic effect

may increase mineral loss. In addition, the phosphoric acid in soda

may contribute to bone loss.Bone density can be improved at any time.

http://www.mayoclinic.com/health/AboutThisSite/AM00057

http://www.mayoclinic.com/health/AboutThisSite/AM00057



32

Soda is the devil’s drink

• Extra calories

• Poor nutrient

density

• Interferes with

calcification

• Replaces more

nutritious drinks



Toxicity

• -***polyuria, constipation, bone pain,

azotemia, coma

• -”stones, bones(bone pain), groans, psychiatric

overtones”



QUIZ

1. Absorption of calcium, location

2. Ca-toxicity

3. Ca-deficiency



Phosphorus

• Levels maintained by parathyroid gland – Easily absorbed by the body

– Enhanced by Vitamin D

– Deficiency are rare

– Soda, phosphoric acid



Functions

• -structure of teeth and bones

• -essential component in cell membranes,

nucleic acids, phospholipids

• -phosphorylation of glucose

• -buffer system in ICF and kidney



absorption

-best occurs when calcium and phos are

ingested in equal amts (milk)

-vit D also increases absorption



sources



Sources

***dietary sources should be restricted in renaldisease (usually see increased phos,decreased Ca)

• -protein sources

• -meat, poultry, fish, eggs, legumes, nuts, milk,

cereals, grains



Renal Disease



Causes of hypophosphatemia

-starvation

-TPN with inadequate phos content

-malabsorption, small bowel bypass

-vit D deficient and vit D resistant

osteomalacia

f h h h i




cont’d -phosphaturic drugs: theophylline, diuretics,bronchodilators, corticosteroids

-hyperparathyoidism (primary or secondary)

-hyperthyroidism-renal tubular defects

-hypokalemic nephropathy

-inadequately controlled DM

-***alcoholism

C f h h h i




cont’d Intracellular shift of phosphorus

-administration of glucose

-anabolic steroids, estrogen, OCP

-respiratory alkalosis-salicylate poisoning

Electrolyte abnormalities

-hypercalcemia

-hypomagnesemia

-metabolic alkalosis

C f h h h i




cont’d Abnormal losses followed by inadequate repletion

-***DM with acidosis—with aggressive therapy

-***recovery from starvation or prolonged catabolic state—

refeeding syndrome

-***chronic alcoholism, especially with nutritional repletion,

assoc with hypomagnesemia—”

-recovery from severe burns



Causes of hyperphosphatemia

-excessive growth hormone (acromegaly)

-hypoparathyroidism assoc with low Ca

-pseudohypoparathyroidism assoc with low Ca

-***chronic renal insufficiency

-acute renal failure

C f h h h t i



Causes of hyperphosphatemia

cont’d Catabolic states, tissue destruction

-stress or injury, rhabdomyolysis (esp with renal

insufficiency)

-chemotherapy of malignant disease, particularlylymphoproliferative disease

Excessive intake or absorption

-laxatives or enemas containing phosphate-hypervitaminosis D



Deficiency

• -fatal

• -usually rare with food intake

• -***respiratory muscle collapse

•-heart failure

• -muscle aches, bone pain, and fracture



Toxicity

• -symptoms of the primary disorder

• cellular functions, ranging from energy

metabolism to cell signalling.



Quiz

1. Function of phosphate

2. Absorption



Magnesium



Function

-bone, muscle contractility, nerve excitability

-antagonistic to calcium

--in a muscle contraction, Mg relaxes, and

calcium contracts

--low Mg can cause pregnancy induced HTN



Absorption / Excretion

• -absorption varies

• -similar to calcium (low pH, upper GI), however, noVit D required-kidney conserves Mg when intake of Mg is low

• -large losses with vomiting because of high levels ofgastic juice



sources



Sources

• -seeds, nuts, legumes, unmilled cereal grains,

dark greens

• -fish, meat, milk, fruits

• -lost during refining of flour, rice, vinegar



Causes of hypomagnesemia

-malabsorption, chronic diarrhea, laxativeabuse

-prolonged GI suction

-small bowel bypass-malnutrition

-***alcoholism

-refeeding-TPN with inadequate Mg



Causes of hypomagnesemia cont’d

-DKA-diuretics

-hyperaldosteronism, Barrter’s syndrome

-hypercalcuria

-renal Mg wasting

-hyperparathyroidism

-postparathyroidectomy

-vit D therapy-aminoglycosides, ***cisplatin, ampho B



Causes of hypermagnesemia

Decreased renal fxn

***Increased intake—abuse of Mg containing

antacids (MOM) and laxatives in renal

insufficiency



Deficiency

• -anorexia, growth failure, cardiac and

neuromuscular changes—weakness,

irritability, mental derangement

• -tetany, muscle cramps



Toxicity

• -respiratory—depression, apnea

• -CV—hypotension, cardiac arrest, EKG(prolonged QRS and QT, heart block, peaked T

waves)• -GI—N/V

• -neuromuscular—paresthesias, somnolence,

confusion, coma, hyporeflexia, paralysis,apnea



Function

• -respiratory transport of O2 and CO2

• -immune system

• -cognitive performance

• -found in Hgb (in RBC’s) and myoglobin (in

muscles)

• -cytochrome p450 system



Absorption and transport

• -dietary iron exists in heme (Hgb and myoglobin) andnon-heme

• -***heme Fe is absorbed better

• -non-heme Fe has to be present in the duodenum orupper jejunum in soluble form if it is to be absorbed

• -in Fe deficiency, 50% can be absorbed

• -***2-10% of Fe from veggies is absorbed and 10-

30% is absorbed from animal protein



Factors affecting absorption

• -***ascorbic acid is the most potent enhancer

• -animal proteins (beef, pork, veal, lamb, liver, fish,chicken) enhance

• -but, proteins from cow’s milk, cheese, eggs, don’t

• -gastric acidity enhances absorption (antacidsinterfere)

• -pregnancy, increased growth, Fe defic all increase

deficiency



• -phytate and tannins decrease abs

• -Fe used for enrichment are less absorbed

than elemental Fe

• -increased intestinal motility decreases

absorption because it decreases contact time

for absorption



Storage

• -stored as ferritin and hemosiderin

• -long term high Fe ingestion or frequent bloodtransfusions can lead to accumulation of Fe in theliver

• -***hemosiderosis develops in individuals whoconsume a lot of Fe or have a genetic defect resultingin increased Fe absorption

• -in associated with tissue damage, it is calledhemochromatosis



Excretion

• -lost thru bleeding, feces, sweat, exfoliation of

hair and skin

• -none in urine



Sources and Intakes

• -best source is liver

• -oysters, shellfish, kidney, lean meat, poultry, fish

• -dried beans, veggies, dark molasses

•

-egg yolks, dried fruit, enriched breads,• -requirements are highest in infancy and adolescence

• -females stay high because of menstruation

• -decrease with menopause and increased with

pregnancy



Deficiency

• -most common deficiency

• -most at risk: <2 yrs old, teens, pregnancy, elderly

• -***anemia (hypochromic, microcytic)

•

-tx: diets high in absorbable Fe and/or Fesupplements (ferrous sulfate, ferrous gluconate)

• -can be caused by injury, hemorrhage, illness, poordiet



Zinc

• -involved in synthesis or degradation of CHO,proteins, lipids, nucleic acids

• -stabilizes RNA and DNA

• involved in transcription and replication• -needed for bone enzymes and osteoblastic

activity



absorption

• Impaired absorption in Crohn’s or pancreatic

insufficiency

• -plasma zinc levels act as acute phase

reactants and fall by 50% with injury (likeplatelets)



Inhibiting Factors

• -fiber, phytate

• -high doses of copper

• -Fe competes with zinc for absorption



Enhancing Factors

• -glucose, lactose, and soy protein

• -red wine

• -human milk



Excretion

• -feces—almost entirely

• -***in urine with starvation, nephrosis, DM,

alcoholism, hepatic cirrhosis (zinc

supplementation in encephalopathy),porphyria



Sources and Intakes

• -meat, fish, poultry, milk

• -oysters, shellfish, meat, liver, cheese, whole

grains, dry beans, nuts



Deficiency

• -short stature, hypogonadism, anemia

• -with diets high in unrefined cereal and unleavened

bread

•-delayed wound healing, alopecia

• ***-acrodermatitis enteropathica=AR dz with zinc

malabsorption

• -eczematoid skin lesions, alopecia, diarrhea, bacterial

and yeast infections, death



• -immunologic deficits—lymphopenia, thymic

atrophy



***Causes of deficiency –

Anorexia Nervosa – TPN without zinc (diarrhea, small bowel fistulas)

– High intake of phytate, tannins, binding drugs (EDTA),oxalate

–

High iron intake – Malabsorption syndromes

– Acrodermatitis enteropathica

– Diarrhea

–

Pancreatico-cutaneous fistula – Proximal entero-cutaneous fistulas

– Hemolytic anemias (sickle cell anemia)

– Renal failure patients on dialysis

*** i fi i



***Zinc Deficiency

42 yo female with chronic uremia on dialysis. Recently started on iron supplement

for anemia. Presents with rash, hypogeusia, hyposmia and poor dark adaptation.

Acrodermatitis



c ode at t s

Enteropathica• Autosomal recessive disease associated

with a defect causing a reduction in zinc

absorption

• Can be treated by pharmacologic doses of

oral zinc

Acrodermatitis



Acrodermatitis

Enteropathica

T i i



Toxicity

• ->100-300 mg/d

• -rare

• -interferes with copper absorption

• -decrease in HDL

• -GI irritation, vomiting

Fl id



Fluoride

• -tooth enamel

• -resistance to dental caries

• -fluoridation of h20 has decreased caries by

half

• -found in drinking h20, teflon pots and pans

(cooked in these)

• -toxicity at doses >0.1 mg/kg/d

P i f d l i



Prevention of dental caries

• ***Incidence of dental fluorosis (mottledteeth) occurs with increased intake above 1-2

ppm.



Mottled teeth in fluorosis

M



Maganese

• -found in many enzymes

• -connective and bony tissue formation

• -growth and reproduction

• -CHO and lipid metabolism

S d I t k



Sources and Intakes

• -whole grains, legumes, nuts, teas, fruit,veggies, instant coffee, and tea

Ab ti d E ti



Absorption and Excretion

• -after absorption, it appears rapidly in the bileand is excreted in the feces

• -concentrated in liver and increases with liver

disease

D fi i



Deficiency

• -wt loss, ataxia, dermatitis, N/V, decreasedhair growth, impaired reproductive activity,

decreased pancreatic function and CHO

metabolism

T i it



Toxicity

• -accumulates in liver and CNS—parkinsoniansx

F



Ironand

Anemia

Fe

1 Iron deficiency (50% of the population in some countries)

Fe



1. Iron deficiency (50% of the population in some countries)

a. Impairs red cell production

b. Affects general cell growth and differentiation, specifically

cells of the nervous system and intestine

c. Characterized by cells that are both microcytic (small) and

hypochromic (low color)

2. Children between ages of 6 and 18 months are more susceptible

a. 10 times the adult requirement at this time

b. Milk is generally a poor source of iron

(1) An iron deficiency will develop if milk is the sole

source of infant iron after 4 months

c. An anemic child tends to be tired and inattentive, motor

skills are delayed, mental retardation, emotional problems

are evident

Fe

Anemia and pregnancy

Fe



p g y

Rule: Pregnant women have double the adult requirement

1. Most of the additional iron is transferred to the fetus

Other Causes of anemia:

1. Lack of vitamin B12 or folate

2. Megaloblastic anemia: release of precursors megalokaryocytes into the blood

3. Pernicious anemia: antibodies to intrinsic factor (B12 absorption)

4. Beta Thalassemia: imbalance in the production of alpha and beta subunits

of hemoglobin

5. Lead poisoning

6. Intrinsic copper deficiency

Fe

Mineral Composition of Mammalian Milk

Fe



p

Calcium 5645 879Sodium 1228 126

Potassium 2669 429

Iron 15 2

Copper 7 2

Zinc 29 6

Manganese 979 363

Mg/Liter

after

Reichlmayr-Lais and Kirchgessner

Rat

Calcium 259 59 1180Sodium 207 94 580

Potassium 543 78 1400

Iron 0.4-0.76 0.2-0.06

Copper 0.2-0.4 0.05-0.2

Zinc 1-3 4

Manganese 3-6 21Magnesium 31.4 5.9 120

Phosphorus 142 25 930

Chloride 453 53 1040

Selenium (ng/g) 15-20 10

Iodine (ng/g) 12-178 70-219

Molybdenum (ng/g) 1-2 22

Chromium (ng/g) 0.2-0.4 5-15

Nickel (ng/g) 0.5-2 4-40

Aluminum (ng/g) 4-14 27

Fluorine (ng/g) 4-15 19

Human Bovine

Mg/Liter

After Picciano

When it comes to minerals, milk

is far from being nature’s

perfect food

Iodine



Iodine

• iodine is necessary for the formation of thyroidhormones (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

Fortification vs Enrichment



• Fortification - restores lost

nutrients due to processing

• Enrichment – adds nutritional value to

meet a specific standardOld LondonRestaurant Style Croutons. SeasonedSourdough.

Enriched Bread,[Enriched Flour(Flour,Niacin,Ferrous Sulfate,

Thiamin Mononitrate,Riboflavin,Folic Acid), Water,Yeast,Sugar,Salt,Partially Hydrogenated Soybean Oil ,Vinegar,Ascorbic Acid]Bean Oil with BHT added as a Dextrin

Silicon



Silicon

• essentiality has been established in chicks andrats, but not humans

• appears to play an important role in thedevelopment and maintenance of cartilage

(chondroitin sulfate, hyaluronic acid, keratinsulfate)

• may have a protective role in cardiovasculardiseases (atherosclerosis)

• found in unrefined grains and beer

Manganese



Manganese

• Maganese is an activator of several differentenzymes:

• Phosphoglucomutase

• Isocitric dehydrogenase

• Cholinesterase

• Intestinal peptidase

• Carboxylases

• ATPases

• However, magnesium and cobalt can replace Mn inseveral enzymes

Manganese



Manganese

• Essential for sulfomucopolysaccharide biosynthesis• Deficiency leads to:

• 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



Chromium

•Cr III may act as a cofactor for insulin, enhancing glucoseutilization

• deficiency leads to impaired glucose tolerance (glucosetolerance 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



Selenium

• prevents:• 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 kidneysin mice

• appears to function in the metalloenzymeglutathione peroxidase, which destroys peroxides inthe cytosol

• no deficiencies have been seen in humans

• has antioxidant activity (may have relationship withvitamin E - sparing action)

Tin



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



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



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 oxidation-reduction

catalyst

Molybdenum



Molybdenum

• Widely found in commonly used foods(cereals, vegetables

• Mo is part of flavoproteins, xanthine oxidase,

aldehyde oxidase

Sulfur



Sulfur

• Most sulfur in the diet comes in from protein sourcescontaining 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



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