Minerals Flashcards
Major minerals
- -Calcium
- -Phosphorus
- -Potassium
- -Sodium
- -Chloride
- -Magnesium
Trace minerals (
- -Iron
- -Zinc
- -Copper
- -Manganese
Ultratrace minerals (
- -Selenium
- -Molybdenum
- -Iodine
- -Chromium
Functions of minerals
- -Maintain osmotic balance
- -Maintain charge/concentration gradients across membrane
- -Enzyme cofactors
- -Structure
- -Taste
What is the major extracellular cation?
Sodium
What is the major intracellular cation?
Potassium
Dietary sources of calcium
Dairy, seafood, turnips, broccoli, kale, dietary supplements
Most abundant metal in the body?
Calcium. About 1.4 Kg in 70 kg man
Functions of calcium
–Bone mineralization
–Signaling molecule for muscle contraction
–Helps regulate
metabolism
Blood clotting
What regulates absorption of calcium?
Calcitriol (Vitamin D)
What chaperones calcium within the cell
Calbindin
What helps increase absorption of calcium?
Vitamin D, sugars, sugar alcohols, protein
What decreases absorption of calcium?
Fiber, phytic acid, oxalic acid, other divalent cations, unabsorbed fatty acids
What increases expression of calcium channel TRPV6 at brush border and alters tight junction permeability to calcium?
Activated VDR
[Ca++] in the blood
8.5-10 mg/dL
40% bound to protein
50% free ionized
10% complexed with sulfate, phosphate, citrate etc.
Cytosolic [Ca++] vs. extraceullular
Very low in cytosol (100nMol).
10,000x higher in extraceullular area (2.3 mmol)
Where is Ca++ stored in cells?
Intracellular compartments
Ca++/ 3Na+ transporter
- -Helps export calcium from cells
- -Low affinity, high capacity
Ca++/2H+ transporter
- -Helps export calcium from cells
- -High affinity, low capacity
Calmodulin
Mediated intracellular signalling by calcium. Protein whose association with other proteins is regulated by calcium binding
What happens when intracellular calcium increased?
Glycogen synthase inactivated and glycogen phosphorylase is activated
Calcium interactions with other dietary components
- -Calcium blocks phosphorus uptake
- -Calcium transiently blocks iron uptake
- -Calcium can trap fatty acids, bile salts in “soaps” that are not digestible
Calcium excretion
- -Urinary: 100-240 mg/day (controlled by calcitriol)
- -Feces: 45-100 mg/day
- -Sweat: 60 mg/day
People at risk of calcium deficiency
- -Fat malabsorption disorders
- -Immobilized patients
Causes of calcium deficiency
Rickets
Tetany
Osteoporosis
Calcium deficiency associated with what?
Colorectal cancer
Hypertension
Type II diabetes
Calcium TUL
2,500 mg/day
Acute calcium toxicity
Constipation, bloating
Chronic calcium toxicity
Calcification of tissue, hypercalciuria, kidney stones, maybe CV disease
Best assessment of calcium status?
Bone density scan
Magnesium dietary sources
Nuts, legumes, whole grains, chlorophyll, chocolate, hard water
Magnesium functions
- -Calcium metabolism
- -Component of bone
- -Muscle contraction
- -Nerve impulse propagation
- -Cofactor in ATPases
- -Needed for kinases and polymerases that use nucleotide triphosphates
- -Needed for activation of Vit D by 25-hydroxlase
Magnesium in body
25 grams
–50-60% in bone, 40-50% in soft tissues, 1% in extracellular fluid
What allows for saturable transport of magnesium across the brush border?
TRPM6
Basolateral transport of magnesium
2Na+/Mg++ antiporter, 2K+/3Na+ ATPase
Is paracellular diffusion of magnesium saturable?
No
How much of the magnesium intracellularly is associated with ATP?
Greater than 90%
Interactions of magnesium with other things in the diet?
- -Can mimic Ca++ and compete for absorption in the kidney
- -Inhibits phosphorus absorption
Best measurement of magnesium status?
Rena Mg++ excretion before and after a loading dose
Magnesium deficiency
- -Dietary deficiency not described (can be induced though)
- -Nausea, vomiting , HA, anorexia. Progresses to seizures, ataxia, fibrillation
- -Chronic deficiency associated w/HTN and DMII
Gitelman syndrome
- -Autosomal recessive mutation of SLC12A3 (thiazide sensitive Na/Cl transporter)
- -Characterized by hypomagnesemia, hypokalemia, hypocalciuria
Magnesium TUL
350 mg/day
Magnesium toxicity
- -Associated with epsom salt use
- -Diarrhea, dehydration, flushing, slurred speech, muscle weakness, loss of deep tendon reflex
- -If higher that 15 mg/dL, can cause cardiac arrest
Chloride dietary sources
Primarily table salt
Chloride absorption
Paracellular or through Na+/Cl- electroneutral transporter
Chloride distribution
Neutrophils and parietal cells
Chloride functions
- -Cl-/HCO3- exchangers–> enters RBCs in exchange for HCO3- when cells deliver oxygen to tissues and leaves RBCs in exchange for HCO3- when cells take in oxygen from the lungs
- -Hypochlorous acid is secreted by neutrophils during phagocytosis to neutralize pathogens
- -Gastric hydrochloric acid secretion by parietal cells
Potassium function
Major intracellular cation, muscle contractility
Potassium regulation
Vasopressin and aldosterone increase urinary K+ excretion (opposite of Na+)
Potassium interactions
Decreases calcium excretion (opposite of Na+)
Hypokalemia causes
Fluid loss, thiazide or loop diuretics, refeeding syndrome
Hypokalemia symptoms
Cardiac arrhythmias, muscular weakness, hypercalciuria, glucose intolerance, mental disorientation
Moderate K+ deficiency is associated with?
Elevated BP, decreased bone density
Hyperkalemia causes and possible effects
Renal failure and can lead to cardiac arrhythmia/arrest
Phosphorus amount in body and distribution
- -850 g
- -85% in bone
- -1% in fluids
- -14% in soft tissue, esp. muscle
Phosphorus sources
Meat, poultry, fish, eggs, dairy, cola (phosphoric acid)
When is saturable carrier mediated active transport used for phosphorus absorption? How is it activated?
When phosphate intake is low. Activated by calcitriol
Where does diffusion of phosphorus occur?
In the proximal duodenum (slightly acidic)
What inhibits phosphorus absorption?
Magnesium, albumin, calcium. All found in antacids and used to treat hyperphosphatemia from kidney failure
Phosphorus functions
- -Bone mineralization
- -Component of DNA and RNA
- -Component of phosphorylated vitamins
- -Traps monsaccharides in cells
- -Activates protein kinase and deactivates glycogen synthase
- -Helps maintain pH
What promotes excretion of phosphorus?
- -Elevated dietary phosphorus
- -PTH
- -Acidosis
- -Phosphotonins
Excretion of phosphorus is inhibited by?
- -Low dietary phosphorus
- -Calcitriol
- -Alkalosis
- -Estrogen
- -Thyroid hormone
- -Growth hormone
Dents disease
X-linked
- -Mutation in renal chloride channel
- -Can lead to phosphate deficiency
Phosphorus deficiency causes
- -Extreme use of antacids
- -Malnourishment
- -Refeeding syndrome
- -Inherited disorders
Phosphorous deficiency symptoms
Anorexia, reduced CO, decreased diaphragmatic contractility, myopathy, death
X-linked hypophosphatemic rickets
- -Mutation in PHEX gene–>elevated FGF-23
- -Can cause phosphorus deficiency
Autosomal dominant hypophosphatemic rickets
- -Mutation in gene encoding FGF-23–> prevents it’s degradation
- -Can cause phosphorus deficiency
Iron dietary sources
Meat, fish, poultry, nuts, fruits, vegetables, grains
How much iron usually in a 70 kg man?
2-4 grams
What form of iron is the reduced form?
Ferrous iron (Fe++)
What form of iron is the oxidized form?
Ferric iron (Fe+++)
- What promotes conversion of ferrous iron to ferric iron? 2. What about ferric to ferrous?
- Ceruloplasmin
2. Low pH
What reduces ferric iron at the brush border
Reductase
Transport of ferrous iron in cell through what?
Divalent metal transporter-1 (DMT-1)
What is iron stored to in a cell?
Ferritin
What is required for iron transport into the blood
Oxidation to Fe+++ by hephaestin (ceruloplasmin). It’s a copper requiring enzyme
What does Fe+++ bind to for transport to tissues?
Transferritin
Main iron reservior
Located in liver. Hemosiderin and ferritin
What is responsible for regulation of iron uptake?
Hepcidin. When iron stores high, hepcidin is produced.
Hepcidin
Binds ferroportin and causes its degradation when iron stores in liver are high
Iron functions
- Heme synthesis used in hemoglobin, myoglobin, monooxygenases, cytochrome B and C
- Iron-sulfur cluster involved in electron transfer groups
- Non heme iron is a dioxygenase
Iron interactions
- -Vit C enhances iron absorption and maintains iron in reduced state
- -Copper needed for iron export from enterocytes
- -Iron inhibits zinc absorption
Iron deficiency observed in?
- -Infants
- -Adolescents (rapid growth)
- -Pregnant women
- -Absorption disorders
Iron deficiency symptoms
- -Microcytic hypochromic anemia
- -Listlessness
- -Fatigue
Iron toxicity TUL and chemistry behind it?
- -45 mg/day
- -Can accumulate in tissues if intake exceeds ferritin storage capacity and can act as a free radical causing oxidative damage
Chronic hemochromotosis
- -Inherited mutations in hepcidin (or other iron metabolism genes)
- -Causes organ failure from iron accumulation
Copper dietary sources
Meat, shellfish, nuts
Normal amount of copper in 70 kg man?
50-150 mg
What reduces Cu++ to Cu+
Brush border reductase
What is responsible for Cu+ transport into cell?
CTR1
What allows for copper to enter the blood?
ATP7A (basolateral transporter)
Menkes kinky hair syndrome
- -Mutations in ATP7A.
- -Hypothermia, hypotonia, poor feeding, FTT
- -Normal hair at birth that becomes brittle and sparse with aging
Functions of copper
- -Cofactor for ceruloplasmin
- -Cytochrome C oxidase needs copper
- -Cofactor for lysyl oxidase (collagen synthesis, requires ascorbate)
- -Cofactor for superoxide dismutase (antioxidant enzyme)
- -Cofactor for dopamine beta-hydroxylase (needed for catecholamine synthesis)
Copper deficiency causes
–Can occur in people who consume a lot of zinc or a lot of PPI
Copper deficiency symptoms
Anemia, leukopenia, hypopigmentation of skin and hair, altered cholesterol metabolism
Copper toxicity (TUL)
10 mg/day
Acute copper toxicity symptoms
Epigastric pain, N and V, diarrhea
Chronic copper deficiency
Hematuria, liver damage, kidney damage
Wilson disease
- -Mutation in ATP7B (liver specific copper transporter)
- -Treatment: avoid high copper foods, chelation therapy
- -Kayser-Fleischer ring
ATP7B
–Normally transports excess copper into bile for excretion
What happens when ATP7B is defective?
Copper accumulates and “leaks out” unbound to ceruloplasmin