Calcium, Phosphate & Vitamin D in Bone Health Flashcards
Bone Mass
actual amount of osseous tissue in any unit volume of bone.
Concentration of ionized
calcium in ECF (plasma)
1.2mmol/L
Calcium in plasma present in
three forms
Combined with plasma proteins-non diffusible Combined with anionic substances in plasma β diffusible but non ionised Ionised form β diffusible (most important form)
Calcium reservoir
About 98 -99% of total body calcium stored in bone
Bones act as the most important reservoir:
βrelease calcium when extracellular calcium drops and
βstore excess calcium
Functions of Calcium
mechanical stability and serves as a reservoir
bone formation and remodeling
important cofactor for several enzymes and signal for signaling pathways
including blood clotting - ensuresthat blood clots normally
β muscle contraction; regulates muscle contractions, including heartbeat
Calcium-Recommended daily allowance
25β30 mmol (1000β1200 mg) for most adults
Absorption and Excretion of Calcium-Intestinal Absorption
β’ Vit D dependent
Absorption and Excretion of Calcium-Bone deposition and
Resorption
Vit D & PTH dependent
Absorption and Excretion of Calcium-β’ Excretion in Kidneys
PTH dependent
Phosphate absorptive efficiency may be enhanced by?
1,25(OH)2D (Vit D)
Excretion of phosphate is through?
urine β controlled according to plasma
concentration levels which can be overridden by PTH
Parathyroid Hormone (PTH) - Effects on Calcium and Phosphate Levels
inc . Calcium
involved in Phosphate homeo
Parathyroid Hormone (PTH) β Effects on Bone
PTH promotes net bone resorption
inc in Calcium
Parathyroid Hormone (PTH) β Effects on Bone
PTH promotes net bone resorption
inc in Calcium
Parathyroid Hormone (PTH) - Effects on the Kidneys
Therefore, PTH would facilitate increased
phosphate excretion from the kidneys, thereby
reducing complex formation and facilitating
increase in availability of free ionized calcium.
PTH increases plasma calcium (Ca++) by:
inc. bone resorption (activates osteoclasts, dec collagen synthesis by osteoblasts).
inc. Ca++ reabsorption in the kidneys
inc. vitamin D synthesis in kidneys,dec. Ca++ absorption in the GIT
PTH on phosphate levels:
dec plasma levels by inc. bone resorption
dec plasma levels by inc. excretion from kidneys
vitamin D2
Ergocalciferol
plant origin
CholecalciferoI
(vitamin D3) of animal origin
precursor for cholecalciferol
synthesis in skin
7-
dehydrocholesterol
Sunlight plays a major role in ?
the conversion of 7-dehydrocholesterol (precursor for cholecalciferol
synthesis in skin) to cholecalciferol
what is 25-hydroxycholecalciferol converted to in the kidney
1,25 β dihydroxycholecalciferol
calcitriol - 1,25-diOH-D3
Actions of -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 stimulate gene expression or repress gene expression (similar to steroid hormones)
Actions of Vitamin D-On the intestine?
-stimulates intestinal absorption of calcium and phosphate by
increased synthesis of a specific calcium binding protein calbindin
-stimulate an ATP-dependent calcium pump, which
transports calcium into the blood stream
Actions of Vitamin D-On the bone ?
-stimulates the mobilization of calcium and phosphate from the
bone by potentiating parathormone
Actions of Vitamin D-On the kidneys
inhibits calcium excretion by stimulating
calcium reabsorption; weak effect
Calcitonin
- Secreted by cells in the thyroid gland
- Inhibits osteoclast activity ( decreases bone resorption)
- Reduces plasma calcium, opposing the effects of PTH
Vitamin D Deficiency causes :
Nutritional deficiency Inadequate skin synthesis Liver disease (reduced 25-hydroxylase activity) Kidney disease (reduced 1-hydroxylase activity)
Vitamin D Deficiency clinical correlation :
- Rickets(in children )
- Osteomalacia (adults)
- Hypocalcemia,
- Hypophosphatemia,
- Increased serum alkaline phosphatase (ALP) from bone
Rickets: In children
- Demineralisation of bone β soft pliable bones
- Characteristic bow-leg deformity
- Overgrowth at costochondral junction β rachitic rosary
- Pigeon chest deformity
- Frontal bossing
Osteomalacia: In adults
ο Weakening of bones β
frequent fractures.
Vitamin D Resistant Rickets
-β’ Plasma levels of 1,25(OH)2D are elevated.
-Caused by mutations in the gene encoding the vitamin D receptor in the intestine - decrease Ca2+ absorption from diet
-Treatment: Difficult. Regular, usually nocturnal calcium infusions, which
dramatically improve growth but do not restore hair growth.
Hypervitaminosis D
-Vitamin D toxicity
- Enhanced calcium absorption and bone resorption results in
hypercalcemia, which can lead to deposition of calcium in many
organs, particularly the arteries and kidneys (soft tissue calcification).
Hypocalcemia causes
- Low Parathyroid Hormone Levels (Hypoparathyroidism)
- High Parathyroid Hormone Levels (Secondary Hyperparathyroidism)
- Hungry bone syndrome after parathyroidectomy
Hypocalcemia lab findings
- 25 hydroxyvitamin D levels β low if nutritional deficiency of vitamin D
- 1,25 dihydroxyvitamin D levels β low if renal insufficiency
- PTH levels β low after parathyroidectomy
Hypocalcemia- clinical features
- hypocalcemic tetany
- excitability of periperal nerves
- carpopedal spasm ,stridor and convulsions
Treatment of hypocalcemia
Ca supplements and vit D
In emergencies: calcium gluconate IV
Hypercalcemia causes :
-Excessive PTH production
β’ Hypervitaminosis
β’ Excessive 1,25(OH)2D production
β’ Excessive calcium intake
Lab findings of hypercalcemia if its due to hypervitaminosiss D
- increase in calcium β
- increase in phosphate
- increase in 1,25 (OH)2 D
Lab findings of hypercalcemia if its due to excessive PTH production
increase in PTH
increase in Ca
decrease in phosphate
Clinical Manifestations of Hypercalcemia
β’ Non-specific signs and symptoms: β Polyuria & polydipsia β Renal calculi ( colic) β Lethargy, β Anorexia and nausea β Peptic ulceration β Depression β Drowsiness β Impaired cognition
Hypophosphatemia Causes:
1) Inadequate intestinal phosphate absorption β vitamin D deficiency,
(2) Excessive renal phosphate excretion β PTH excess.
Hypophosphatemia: Symptoms
Nerve, bone, red and white blood cells, membrane, and muscle
functional problems
Serum levels of phosphate and calcium must be monitored
closely (every 6 β12 h) throughout treatment.
Hyperphosphatemia- Causes
-Decreased renal excretion - Impaired kidney function
β’ Hypoparathyroidism
β’ Excessive release of phosphate into the ECF (from the gut, bone or parenteral phosphate
therapy)
Hyperphosphatemia-Clinical effects:
-Calcification of soft-tissue, organs (kidney, lungs, heart)
β’ Tetany,
β’ Seizures.
Hyperphosphatemia-Lab finding:
β’ Fasting serum phosphate concentration >1.8 mmol/L (5.5 mg/dL),
