Calcium, Phosphate & Vitamin D. In Bone Health Flashcards
What is the mechanical function of bone?
Allowing effective muscle contraction and movement
How do bones affect transduction ?
Transduce sound waves from ear drum to the inner ear
What do bones produce within the marrow?
Within their marrow: bones produce red and white blood cells as well as growth factors; and store fatty acids as yellow marrow
What do bones store?
Storage of certain minerals: including calcium & phosphorous and, to a lesser extent, zinc, copper and sodium
Temporarily absorb and store toxic heavy metals: to reduce their effects on the body
What are the functions of bones?
- mechanical
- protection
- Transduce sound waves
- bone marrow produces blood cells, growth factors and stores fats
- stores minerals & toxic heavy metals
What is bone?
A composite material consisting of a fibrous prptein(collagen) stiffened by an extremely dense filling and surrounding of calcium phosphate crystals. There are other constituents.
Summarize chemical composition of bone
Bone is made up of the inorganic mineral hydroxyapatite- calcium apatite or, in its crystal-structure form
What is bone mass?
Bone tissue (osseous tissue and soft tissue) is remodeled constantly throughout life
Bone mass: actual amount of osseous tissue in any unit volume of bone
What are the intrinsic determinants of bone mass?
Genetics.
- gender
- family history
What are the extrinsic determinants of bone mass?
- diet
- body mass/hiatus
- hormonal milieu
- (PTH, Vit D & estrogen)
- illnesses
- exercise
- lifestyle choices
What 3 forms does calcium exist in plasma?
- combined with plasma proteins- nondiffusible
- combined with anionic substances in plasma- diffuse leg but non ionized
- ionized form-diffusiblev(most important firm)
What is the concentrations of calcium in plaasma?
In ECF(plasma) ionized- 1.2 mmol/L
Protein bound calcium- 1.0 mmol/L
Calcium complexed to anions- 0.2mmol/L
Summarize the amount of calcium in bone reservoirs
-about 98%-99% of total calcium stored in bones
Bones act as the most important reservoir:
- release calcium when extracellular calcium drops and
- store excess calcium
Contrast the function of osteoclasts and osteoblasts
Osteoblasts- free ionized calcium to calcium in bone matrix/ reservoir (mineralization)
Osteoclasts- calcium bone matrix/reservoir to free calcium (resorption)
What are the functions of the calcium?
- calcium is an essential mineral
- there is more calcium in the body than any other mineral
- Calcium in bone provides mechanical stability and serves as a reservoir sometimes needed to maintain extracellular fluid calcium concentration
- Required for bone formation and remodeling: to build strong bones and teeth
- Important cofactor for several enzymes and signal fir signaling pathways I.e.(diacylglycerol, IP3)
- Including blood clotting- ensures that blood clots normally
- muscle contraction; regulates muscle contractions, including heart beat
-Neurotransmitter for some neuron signals and plays a prominent role in maintain8ng the resting membrane potential
What are the sources of calcium?
- milk, cheese and other dairy foods
- green leafy vegetables-but not spinach
- soy beans, tofu, soya drinks with added calcium
- fish with edible bones- such as sardines
- nuts
What is the recommended daily allowance for calcium?
Recommended daily allowance: 25-30nmmol(1000-1200 mg) for most adults
Calcium and milk do have beneficial influences on bone mineral density
-Long-term low Ca2+ intake impair peak bone mass (PBM) development
Humans cannot adapt to very low intakes of dietary calcium. This can cause rickets without vitamin D deficiency
What chemicals are calcium absorption and excretion dependent on?
- Intestinal absorption
- Votamin D dependent
- Bone deposition and resorption
- Vitamin D & PTH dependent
- Excretion in kidneys
- PRH dependent
Explain absorption and excretion of phosphorous
- 85% of the 600 g of body phosphorous is present in bone mineral
- Unlike calcium, phosphorous exists intracellularly at concentrations close to those present in ECF (e.g., 1-2 mmol/L)
- In cells and in the ECF, phosphorous exists in several forms, predominantly as H2PO4^- or NaHPO4^- , with perhaps 10% as HPO4^2-. This mixture of anions will be refferred to here as “phosphate”.
- phosphate is widely available in folds and is absorbed efficiently by the small intestine .
- Phosphate absorptive efficiency May be enhanced by 1,25(OH)2D(Vit D)
Excretion of phosphate is through urine- controlled according to plasma concentration levels which can be overridden by PTH
What is the effect of PTH on calcium and phosphate levels?
-increases calcium ions (thus preventing hypocalcemia)
Incolved in phosphate homeostasis
PTH is stimulated by low calcium
What is the effect of PTH on bone?
-PTH promotes net bone resorption , increasing plasma calcium concentration
Causes:
Osteoblasts increase cytokines (M-CSF, IL-6)
- Proliferation of osteoclasts
- increased bone resorption (demineralization)
- increased plasma calcium and increased plasma PO4
Increases calcium and phosphate release from bone(increased demineralization)
What are the effects of PTH on kidneys?
If both calcium and phosphate levels increase due to PTH:
-Calcium would complex with phosphate to form calcium phosphate
- Recall that it is the free ionized form of calcium that is active
- Due to the CaPO4 complex formation, PTH would not be effective in increasing extracellular calcium levels
- Therefore, PTH would facilitate increased phosphate excretion from the kidneys, thereby reducing complex formation and facilitating increase in availability of free ionized calcium
How does PTH increases plasma calcium?
- bone resorption (activates osteoclasts, decreased collagen synthesis by osteoblasts
- calcium Reabsorption in the kidneys
- vitamin D synthesis in kidneys leads to increased calcium absorption in GIT
What is vitamin D?
A fat soluble vitamin with hormone like function
Ergocalclferol-vitamin D2. Of plant origin
Cholecalciferol-vitamin D3 of animal origin
Sunlight plays a major role in the conversion of 7- dehydrocholesterol (precursor for cholecalciferol synthesis in skin) to cholecalciferol
Over the counter supplements
Summarize the metabolism and action of vitamin D
25-hydroxycholecalciferol in kidney—> 1,25-dihydroxycholecalciferol (calcitriol- 1,25-diOH-D3)
1,25-diOH-D3 binds to intracellular receptor proteins
1,25-diOH-D3 receptor complex interacts with DNA in the nucleus of target
Can either selectively stimulates gene expression or repress gene expression (similar to steroid hormones)
What are the actions of vitamin D in on the intestine?
- stimulates intestinal absorption of calcium and phosphate by increased synthesis of a specific calcium binding protein calbindin
- May also stimulate an ATP-dependent calcium pump, which transports calcium into the blood stream
What are the actions of vitamin D in the bone?
- stimulates the mobilization of calcium and phosphate from the bone by potentiation parathormone
- In smaller quantities, promotes bone calcification
What are the actions of vitamin D on the kidneys?
Inhibits calcium excretion by stimulating calcium Reabsorption; weak effect
What is calcitonin?
Calcitonin is a peptide hormone
Secreted by cells in the thyroid gland in humerus
- INHIBITS osteoclast activity (decreased bone resorption)
- reduces plasma calcium , opposing the effects of PTH
Summarize vitamin D and PTH on calcium and Pi levels
- vitamin D increases serum Ca2+ and PO4
- vitamin D and PTH act synergistically on ca,Fiume in the kidneys
- PTH decreases PO4 Reabsorption in kidneys, lowering serum PO4
What causes vitamin D deficiency in nutritional deficiency?
Decreased intake/fat malabsorption
-cystic fibrosis, celiac disease, Whipple’s disease, Crohn’s disease
How can inadequate skin synthesis lead to vitamin D deficiency?
- inadequate exposure to sunlight
- sunscreens, protective clothing
What common diseases lead to vitamin D deficiency?
Liver disease (reduced 25-hydroxylase activity)
Kidney disease( reduced. 1-hydroxylase activity)
What is the result of vitamin D deficiency in children?
Rickets
- demineralization of bone-soft pliable bones
- characteristic bow-leg deformity
- overgrowth at costochondral junction-rachitic rosary
- pigeon chest deformity
- frontal bossing
What is the result of vitamin D deficiency in adults?
Osteomalacia
Weakening of bones- frequent fractures
What are the lab findings of vitamin D deficiency?
- hypocalcemia
- hypophosphatemia
- increased serum alkaline phosphatase (ALP) from bone
What are the symptoms of vitamin D resistant rickets?
- similar symptoms as classical rickets + alopecia (hair loss)
- plasma levels of 1,25(OH)2D are elevated
What causes vitamin D resistant rickets ?
Caused by mutations in the gene encoding the vitamin D receptor in the intestine —> decreased calcium absorption from diet
What are the treatments of vitamin D resistant rickets?
Difficult. Regular, usually nocturnal calcium infusions, which dramatically improve growth but do not restore hair growth
Explain vitamin D toxicity/hypervitaminosis D
- like all fat-soluble vitamins, vitamin D can be stored in the body and is only slowly metabolised
- high dishes (100,000 IU for weeks or months) can cause loss of appetite, nausea, thirst, and stupor. (Non-specific symptoms)
- enhanced calcium absorption & bone resorption results in hypervalcemia, which can lead to deposition of calcium in many organs, particularly the arteries and kidneys (soft tissue calcification)
