Calcium, Phosphate, and Iron Flashcards
Physiological Calcium
Human body with 830g ♀ and 1100g ♂ of Ca2+
99% in teeth and bones as hydroxylapatite
1% circulating or within cells
Hydroxylapatite
Functions
- In slow, dynamic eq. with soluble Ca2+
- Structural role
- Reservoir for Ca2+ and base
Circulating/Intracellular Calcium
Functions
Critical role in metabolism and cellular processes:
- Ca2+/calmodulin signaling
- IP3 signal transduction cascade
- neurotransmitter secretion
- muscle contraction
- electrical signaling
- blood clotting, osteocalcin, and other 𝛾-carboxyl-containing proteins that depend on Vit K
Dietary Calcium
-
Dairy products
- milk, cheese
- lactose aids in absorption for infants only
-
Green vegetables
- broccoli, kale, collard greens
- spinach calcium poorly absorbed d/t oxalate salts
- Tortillas w/ lime
-
Fish with soft bones
- sardines, canned salmon
- Fortified fruit juices
Calcium
RDA & Toxicity
RDA Levels:
- Low in early childhood
- ↑ throughout teenage years: 1,300 mg/day during max bone mineralization
- adults: 1,000 mg/day
- elderly: 1,200 mg/day for ♂>70, ♀>50
Toxicity:
-
No effects up to 2,400 mg/day
- maybe some constipation
- Higher amounts → kidney stones
Calcium Supplementation
-
Insoluble calcium salts (CaCO3)
- poorly absorbed with achlorhydria if taken w/o food
- well-absorbed w/ food
-
Calcium citrate salts
- do not have to be taken with food
Calcium
Absorption
Absorbed in duodenum and upper jejunum:
-
Paracellular
- driven by transepithelial potential & H2O bulk flow
-
Transcellular
- depends on transporters
- major path
-
⊕ by Vit D
- ↑ TRPV5/6, NCX1, and calbindin
- more important with Ca2+ poor diet
Phosphate Sources
-
Inorganic phosphate present as phosphate or related compounds (e.g. pyrophosphate)
- Abundant in many foods
- Easily absorbed
- Overnutrition > undernutrition in Americans
- Chronic acidosis or aluminum hydroxide in antacids can deplete body phosphorus stores
- At physiological pH: mix of HPO42- and H2PO4-
- Phosphorus content of foods/plasma expressed as amount of elemental phosphorus [P]
-
Found in:
- most seafoods
- nuts
- grains
- legumes
- cheeses
Calcium/Phosphate Balance
Ca2+/P intake ratio of 1-1.4 to 1 recommended.
-
↑ [phosphate]plasma → ↑PTH & ↓calcitriol
⟾ bone demineralization → Ca2+release → osteopenia/osteoporosis
⟾↑Ca2+reabsorption by kidneys → ↑ [Ca2+]plasma → metastatic calcification
Bone Matrix Formation
Calcium, phosphate, and protein required.
Bone remodeling:
-
Mineralization dominates early in life
- Rises rapidly during adolescence
- Bone density peaks ~ 20-30 y/o
-
Demineralization then dominates
- Occurs slowly then rapidly
- Ca2+ lost
- Women with rapid ∆ after menopause
- Vit D & calcium supplements may ↓ risk of osteoporosis
Bone Mass
Peaks ~ 20 to 30 y/o.
Women with rapid decline after menopause.
Factors Effecting
Calcium Levels
[Ca2+]plasma depends on:
-
Intestinal Ca2+ absorption
- relies on dietary Ca2+ and active transport
- determined by calcitriol levels
- controlled by Vit D status
- determined by calcitriol levels
- relies on dietary Ca2+ and active transport
- Release from bone
- Ca2+ excretion by kidneys
Calcium/Phosphorus
Hormonal Control
PTH released when [Ca2+]plasma low:
- ⊕ calcidiol → calcitriol ⟾ ⊕ Ca2+ absorption
- ⊕ Ca2+ reabsorption by kidneys
- ⊕ osteoclasts ⟾ Ca2+ release from bone
Cacitonin released when [Ca2+]plasma high:
- Opposes PTH action in animals
- Blocks Ca2+ reabsorption
- Promotes bone mineralization
- Minimal role in human Ca2+ and phosphate homeostasis
Calcium Homeostasis
Summary
Calcium Excretion
Regulation
Most renal Ca2+ reabsorption occurs in proximal tubule via paracellular route.
-
Junctional permeability partially due to claudin-2
-
High salt diets → ⊖ claudin-2 synthesis → ⊖ Ca2+ reabsorption → ⊕ Ca2+ loss
- long term ⟾ risk of bone demineralization
-
High salt diets → ⊖ claudin-2 synthesis → ⊖ Ca2+ reabsorption → ⊕ Ca2+ loss
-
Estrogen conserves Ca2+ by ⊕ renal reabsorption
- post-menopausal women w/ ⊕ urinary Ca2+ loss ⟾ bone demineralization ⟾ osteoporosis
Calcium & Vit D
Summary
Hypocalcemia
Low [Ca2+]plasma suggests malabsorption or hypoparathyroidism over dietary deficiency.
Low [albumin]plasma can show as low [Ca2+]plasma because it binds calcium.
Symptoms include:
- paresthesias
- muscle cramps
- arrhythmias and cardiac arrest (rare)
- bone fractures
- loss of height d/t spine compression
Hypercalcemia
- Can result from hyperparathyroidism
- parathyroid adenoma
- cancer releasing parathyroid hormone-related peptide (PTHrP)
- Can lead to heart block or cardiac arrest
Osteoporosis
Risks & Tests
Results from uncoupling of bone formation from resorption.
-
Risk factors include:
- family hx
- menopause before 48 y/o
- caucasian/asian race
- inadequate exercise
- inadequate intake calcium/vit D
- small bone frame
- smoking, alcohol abuse, excessive caffeine
- prolonged use of some meds (methotrexate)
- chronic diseases that cause bone loss
- renal failure, chronic malabsorption, diabetes
- DEXA scan used to assess bone density
-
High homocysteine levels weaken bone
- prevents collagen cross-linking
Osteoporosis
Treatments
-
Fosamax (bisphosphonate)
- slows osteoclast activity & bone breakdown
- prevents farnesylation of GTPases needed for attachment
- slows osteoclast activity & bone breakdown
-
Forteo (recombinant PTH fragment)
- activates osteoblasts > osteoclasts
- increases bone growth
Bone Health
Suggestions
- 1:1 dietary ratio of calcium to phosphorus
- avoid excess NaCl
-
get adequate protein
- excess protein + low calcium = bad for bones
-
weight-bearing exercises
- promotes bone formation
Iron
Absorption
2 forms of dietary iron:
-
Heme iron
- better absorbed (10-12%)
-
Inorganic iron
- < 10% absorbed
- Fe2+ >> Fe3+
- depends on particular salt
-
co-ingestion with Vit C enhances absorption
- ascorbate reduces Fe3+ to Fe2+
-
lactoferrin in breast milk greatly improves rate of absorption
- but [iron] in breast milk low
Iron
Requirements
RDA
10 mg for ♂
10 mg for post-menopausal ♀
15 mg for ♀ age 11-50
Assumes 10% bioavailability.
Regular intense exercise up to 30% greater requirements.
Sources of Iron
- meats
- eggs
- oysters
- dark green leafy vegetables
- legumes
- whole grains
Iron
Transport
Transported in blood bound to transferrin.
[Transferrin]plasma determines total iron-binding capacity (TIBC).
Normally only ~35% saturated.
At low saturation levels, iron absorption can be up-regulated.
Iron
Storage
Stored in liver, marrow, spleen, and muscles bound to ferritin.
Saturation of apoferritin ⟾ appearance of hemosiderin.
Iron Deficiency Anemia
Causes and Characteristics
Iron deficiency most common nutritional deficiency worldwide.
Most common cause of anemia in the U.S.
-
Causes:
- poor intake
- excessive blood loss
- dialysis
- low Vit A
- some inflammatory diseases
Iron Deficiency Anemia
Symptoms
- Early stage:
- relatively asymptomatic
- Middle stage:
- fatigue
- anorexia
- reduced immunocompetence
- difficulty maintaining body temp
- abnormal cognitive development in children
- premature delivery in pregnant women
- Final stages
- hypochromic, microcytic anemia
Iron Deficiency Anemia
Assessment and Treatment
- Test:
-
Transferrin content of blood
- ↑ TIBC
- ↓ %transferrin saturation
-
Transferrin content of blood
- Treat:
- Ferrous iron supplements recommended if dietary doesn’t work
Iron Toxicity
- Usually seen in children
- Due to supplement over-ingestion
- Can be fatal
Hemochromatosis
Genetic condition with iron excess.
- Causes:
- Most commonly due to HLA-linked hemochromatosis gene (HFE)
- HFE likely ↓ hepcidin
- Less common due to transferrin receptor 2, ferroportin, hepcidin, or ferritin genes
- Most commonly due to HLA-linked hemochromatosis gene (HFE)
- Symptoms:
- fatigue
- weakness
- chronic abdominal pain
- aching joints
- impotence
- cirrhosis
- heart failure
- Lab tests:
- TIBC
- serum iron
- serum ferritin
- ratio of serum iron:TIBC > 60%
- iron overload per se = %transferrin sat > 50%
- Treat with phlebotomy and iron avoidance
