Minerals

Dr Reed Berger

Nutrition Course Director

Visiting Clinical Professor GI/Nutrition

General Lecture Format -test questions will come from clinical

correlations--these will be relevant in clinical training and practice

-RDA’s and food sources—see Institute of Medicine website (food and nutrition, DRI—elements)—also on nutrition website

-will not be tested on this! Contact me if you have problems with the website

-items with *** and those with photos are important!!

Minerals A naturally occurring , homogeneous,

inorganic substance required by humans in amts of 100 mg/day or more -functions -high and low serum levels -absorption -excretion -deficiency -toxicity

Calcium

-most abundant mineral in the body

-1.5 to 2% of body wt

-99% of calcium is in the bones and teeth

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

Skeletal Calcium -available in non-exchangeable and

exchangeable pools -non-exchangeable is for short term

homeostasis -exchangeable is used for increased needs

(growth, pregnancy, lactation) and is accumulated when diet has adequate calcium

-if there is no reserve, calcium is drawn from bone—leading to deficiency

Serum Calcium -levels: 8.8 to 10.8 mg/dl 3 fractions

1) free/ionized—50% 2) complexed with phos, bicarb, citrate—5% 3) protein bound with albumin or globulin—45%

-***when albumin is low (malnutrition, liver dz), calcium is decreased in ratio of 0.8 mg of calcium to every 1 g of albumin (for each gram of albumin below 4, add 0.8 to calcium level)

-factors such as pH and changes in plasma protein affect distribution

-ionized calcium is increased in acidosis and decreased in alkalosis

-total calcium changes with plasma protein but ionized remains the same ***-example: in resp alkalosis, total serum calcium

is normal, but ionized is low—always check ionized level with acid/base disorders

Functions -building and maintaining bones and teeth -transport fxn of cell membranes and

membrane stabilizer ***-nerve transmission and regulation of

heartbeat—use calcium gluconate IV to treat hyperkalemia (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 the

duodenum -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 (upper

duodenum) -HCL in stomach allows better absorption in

the proximal duodenum -taking calcium with food increases abs -fat increases intestinal transit time and

increases absorption

Factors that decrease absorption -***lack of vitamin D -oxalic acid forms insoluble complex which

decreases absorption (rhubarb, spinach, chard, beet greens)

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

-alkaline medium decreases abs.(lower GI tract) -physical/mental stress increases absorption -aging decreases absorption efficiency (to be

discussed with vit D)

Maintenance of serum level -parathormone (PTH) by the parathyroid gland and

thyrocalcitonin secreted by the thyroid gland maintain serum levels

-***with decreased serum calcium levels, PTH increases and causes transfer of calcium from bone to blood to increase serum levels

-decreased levels also cause kidney to reabsorb calcium more efficiently (might normally be excreted in the urine) and to increase intestinal absorption

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

Maintenance of serum level cont’d ***-always need to correct low Mg level

before treating a low calcium level -calcium may correct by itself -hypomagnesemia decreases tissue

responsiveness to PTH

Causes of hypocalcemia

Decreased Intake or absorption

-***malabsorption

-small bowel bypass, short bowel

-vit D deficiency

Increased Loss

-alcoholism

-***chronic renal insufficiency

-***diuretic therapy

Causes of hypocalcemia cont’d

Endocrine Disease

-hypoparathyroidism

-***hypomagnesemia

-sepsis

-pseudohypoparathyroidism

-calcitonin secretion with medullary carcinoma of the thyroid

Causes of hypocalcemia cont’d

Physiologic Causes

-***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 hypercalcemiaIncreased intake or absorption

-milk-alkali syndrome-vit D or vit A excess

Endocrine Disorders-primary hyperparathyroidism-secondary hyperparathyroidism (renal insuff, malabsorption)-acromegaly-adrenal insufficiency

Causes of hypercalcemia cont’d

***Neoplastic Disease-tumors producing PTH-related proteins (ovary, kidney, lung)-***mets to bone-lymphoproliferative disease including multiple myeloma-secretion of prostaglandins and osteolytic factors

Causes of hypercalcemia cont’d

Miscellaneous causes

-***thiazide diuretic

-sarcoidosis

-paget’s disease of bone

-***immobilization

-familial hypocalciuric hypercalcemia

-complications of renal transplant

-iatrogenic

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

RDA -see handout

Deficiency 1)***bone—to be discussed in osteoporosis

lecture 2) tetany—decreased serum levels increase the

irritability of nerve fibers resulting in muscle spasms, fatal laryngospasm ***-Chvostek’s sign: contraction of the facial m. after

tapping 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

Toxicity -***polyuria, constipation, bone pain,

azotemia, coma -”stones, bones(bone pain), groans,

psychiatric overtones”

Vitamin D -to be discussed in the fat-soluble

vitamin lectures in more detail -but, some key points that may be

clinically relevant…..

-the two main sources of Vit D production are the vit D made in our skin from UV light and that taken up in the diet

-as little as 20 minutes of UV exposure 3x/wk is good even without dietary intake

-liver and the kidney are both needed for synthesis of the active form

-***disease of either organ can lead to low Vit D levels and problems with calcium regulation

-***elderly are especially at risk because of lack of sunlight and renal insufficiency with age

-northern climates that have less sun exposure, get the vitamin from diet (fatty fish such as salmon)

-osteoporosis and osteomalacia -***think of Vit D deficiency in pts with abnormal

calcium levels, osteopenia or osteoporosis, malabsorption, and/or kidney/liver disease

Phosphorus -2nd to calcium in abundance -80% is calcium phos crystals in bones

and teeth -remainder is in every cell and ECF -levels maintained by the parathyroid

gland

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

RDA -see table (and for all RDA’s)

Sources **see handout for sources and RDA ***dietary sources should be restricted

in renal disease (usually see increased phos, decreased Ca)

-protein sources -meat, poultry, fish, eggs, legumes,

nuts, milk, cereals, grains

Renal Disease -need to monitor phos levels to prevent renal

osteodystrophy (osteitis fibrosa and osteomalacia seen in renal dz)

-***used to use phos binders in renal dz, but caused aluminum toxicity—irreversible CNS and bone dz

-***now use Ca Carbonate supplements tid as phos binders

-don’t supplement vit D until phos is controlled because vit D increased calcium and phos absorption

Causes of hypophosphatemia

Diminished supply or absorption-starvation-TPN with inadequate phos content-malabsorption, small bowel bypass-absorption blocked by oral aluminum hydroxide or bicarb (to be discussed)-vit D deficient and vit D resistant osteomalacia

Causes of hypophosphatemia cont’dIncreased loss

-phosphaturic drugs: theophylline, diuretics, bronchodilators, corticosteroids-hyperparathyoidism (primary or secondary)-hyperthyroidism-renal tubular defects-hypokalemic nephropathy-inadequately controlled DM-***alcoholism

Causes of hypophosphatemia cont’dIntracellular shift of phosphorus

-administration of glucose-anabolic steroids, estrogen, OCP-respiratory alkalosis-salicylate poisoning

Electrolyte abnormalities-hypercalcemia-hypomagnesemia-metabolic alkalosis

Causes of hypophosphatemia 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 hyperphosphatemiaEndocrine disease

-excessive growth hormone (acromegaly)

-hypoparathyroidism assoc with low Ca

-pseudohypoparathyroidism assoc with low Ca

Decreased excretion

-***chronic renal insufficiency

-acute renal failure

Causes of hyperphosphatemia cont’d

Catabolic states, tissue destruction

-stress or injury, rhabdomyolysis (esp with renal insufficiency)

-chemotherapy of malignant disease, particularly lymphoproliferative disease

Excessive intake or absorption

-laxatives or enemas containing phosphate

-hypervitaminosis D

Deficiency -fatal -usually rare with food intake -***respiratory muscle collapse -hemolytic anemia -increased infection -platelet dysfxn w/ petechiae -encephalopathy -heart failure -muscle aches, bone pain, and fracture

Toxicity -symptoms of the primary disorder

Magnesium -ranks second to calcium as intracellular

cation -60% in bone, 26% in muscle,

remainder in soft tissues, body fluids -1/2 is free, 1/3 is bound to albumin,

remainer is in bone and not exchangeable

Function

-bone, muscle contractility, nerve excitability

-antagonistic to calcium

-excess Mg inhibits bone calcification

-in a muscle contraction, Mg relaxes, and calcium contracts

-excessive calcium induces signs of typical Mg deficiency

-low Mg can cause pregnancy induced HTN

Absorption / Excretion -absorption varies -similar to calcium (low pH, upper GI),

however, no Vit D required -as dietary calcium decreases, Mg absorption

is increased-kidney conserves Mg when intake of Mg is low

-large losses with vomiting because of high levels of gastic juice

Sources -seeds, nuts, legumes, unmilled cereal

grains, dark greens -fish, meat, milk, fruits -lost during refining of flour, rice, vinegar

Causes of hypomagnesemiaDiminished absorption or intake

-malabsorption, chronic diarrhea, laxative abuse-prolonged GI suction-small bowel bypass-malnutrition-***alcoholism-refeeding

-TPN with inadequate Mg

Causes of hypomagnesemia cont’d

Increased loss-DKA-diuretics-hyperaldosteronism, Barrter’s syndrome-hypercalcuriarenal Mg wasting

Unexplained-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

Iron -30-40% is in the storage form -90% is reused by the body

Function -respiratory transport of O2 and CO2 -immune system -cognitive performance -found in Hgb (in RBC’s) and myoglobin (in

muscles) -ATP production in mitochondria involves both

heme and non-heme enzymes -cytochrome p450 system

-***plays a role in immunity because neutrophils work better when not iron deficient

Absorption and Transport -transferrin—transports Fe in blood to

erythroblasts for use in heme synthesis -dietary Fe deficiency is reflected first

by decreased Tf levels

-dietary iron exists in heme (Hgb and myoglobin) and non-heme

-***heme Fe is absorbed better -non-heme Fe has to be present in the

duodenum or upper 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 (antacids

interfere) -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 -30% is in the liver, 30% in the bone marrow, rest

in spleen and muscles -long term high Fe ingestion or frequent blood

transfusions can lead to accumulation of Fe in the liver

-***hemosiderosis develops in individuals who consume a lot of Fe or have a genetic defect resulting in increased Fe absorption

-in associated with tissue damage, it is called hemochromatosis

Excretion -lost thru bleeding, feces, sweat,

exfoliation of hair and skin -none in urine -amts to about 1mg in the adult male

and less in nonmenstruating females -loss of Fe with menstruation is

0.5mg/day

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 Fe

supplements (ferrous sulfate, ferrous gluconate)

-can be caused by injury, hemorrhage, illness, poor diet

Zinc -involved in synthesis or degradation of CHO,

proteins, lipids, nucleic acids -metallothionein is the most abundant zinc

containing protein -abundant in the nucleus where it stabilizes

RNA and DNA and in chromatin proteins involved in transcription and replication

-present in bone and is needed for bone enzymes and osteoblastic activity

Absorption -balance maintained by absorption and

excretion from intestine -zinc levels are dose-responsive post-

prandially -protein-rich meal promotes zinc

absorption by forming more absorbable zinc—AA complexes

Impaired absorption in Crohn’s or pancreatic insufficiency

-plasma zinc levels act as acute phase reactants and fall by 50% with injury (like platelets)

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

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

Decreased absorption High intake of phytate, tannins, binding drugs (EDTA), oxalate High iron intake Malabsorption syndromes Acrodermatitis enteropathica

Increased loss Diarrhea Pancreatico-cutaneous fistula Proximal entero-cutaneous fistulas Hemolytic anemias (sickle cell anemia) Renal failure patients on dialysis

***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 Enteropathica Autosomal recessive disease

associated with a defect causing a reduction in zinc absorption

Can be treated by pharmacologic doses of oral zinc

Acrodermatitis Enteropathica

Toxicity ->100-300 mg/d -rare -interferes with copper absorption -decrease in HDL -GI irritation, vomiting

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

Abundant in nature with varying amounts naturally found in water supplies

Epidemiologic studies have demonstrated inverse relationship between fluoride intake during tooth development and dental carries prevalence

Fluoride

Prevention of dental caries Numerous interventions have demonstrated

that an intake of ~1.0 ppm of fluoride reduces dental caries by as much as 70%

Possible beneficial effect on prevention of osteoporosis

***Incidence of dental fluorosis (mottled teeth) occurs with increased intake above 1-2 ppm.

Mottled teeth in fluorosisMottled teeth in fluorosis

ppm

Maganese -10 to 20 mg in body -mainly in mitochondria -found in many enzymes -connective and bony tissue formation -growth and reproduction -CHO and lipid metabolism

Absorption and Excretion -carried by transmagnin -after absorption, it appears rapidly in

the bile and is excreted in the feces -concentrated in liver and increases with

liver disease

Sources and Intakes -whole grains, legumes, nuts, teas, fruit,

veggies, instant coffee, and tea

Deficiency -wt loss, ataxia, dermatitis, N/V,

decreased hair growth, impaired reproductive activity, decreased pancreatic function and CHO metabolism

Toxicity -accumulates in liver and CNS—

parkinsonian sx