Calcium homeostasis Flashcards
Why do we need calcium?
Intracellular -basal level ~10^-7M (v low) -signalling molecule -kept low by Ca2+ATPases in mito Vital for enzymes High concs 'toxic' Extracellular -levels ~10^-3M (much higher) -tissue mineralisation Gradient involved in membrane excitability (nerve conduction)
Calcium functions
Communication between neurons
Muscle contraction
Exocytosis
Blood clotting
Calcium pools
Intracellular in organelles e.g. SER, mitochondria
Extracellular in blood and lymph
-controlled by intake (GI) and excretion (kidney)
Bone: dynamic, daily turnover
Phosphate
Always considered with calcium -co-regulated -bone huge store of both ions Functions -component of DNA, RNA, ATP -phospholipids -acid-base buffer in 2 forms: HPO42-, H2PO4-
Phosphate plasma conc.
3.5-4mg/dL
Plasma conc.
Maintenance of plasma conc Ca2+ essential
- 9.2-10.4 mg/dL
- 45% as free Ca2+
- rest bound to serum proteins e.g. albumin, not physiologically active
Dietary calcium
Calcium found in many foods -semame seeds 6g/kg -milk 2g/l -brassicas 1.5g/kg Availability affected by -lactose: > absorption -certain amino acids -phytate (inositol hexaphosphate IP6) < absorption -oxalates < absorption
Diet: adult and children requirement
Adults: daily intake to overcome losses - GI and kidney
Children: uncontrollable losses, needed for construction of new tissues
Teenagers need most
G.I. tract
Site of absorption
Calcium
-active, transcellular absorption occurs in duodenum when low Ca intake, ehanced by carrier protein calbindin, synthesis of which dependent on Vit D
-passive, paracellular absorption occurs in jejenum and ilium & colon to < extent
-uptake prop. to need (Vit D), rarely > 80%
Phosphate: passive & active
Kidneys
Site of excretion
-50% of total Ca plasma appears in filtrate
-load of 10g/day
Site of reabsorption
-phosphate up to 100%
-calcium < 99%
Important target for control (parathyroid hormone): thick ascending limb and distal nephron
Summary intake/ losses calcium balance
Adult - obligatory loss replaced by diet
- diet: ~0.5-1.5g ingested/ day, 0.8g/day excreted
- GI: absorption 0.25-0.5g/day, secretion
- kidney: 10g Ca filtered/ day, 0.15-0.3g appears in urine
- bone: 1kg stored Ca, ~0.5g/day released by resorption or deposited during bone formation
Bone composition provides for strength and resilience
Minerals resist compression, collagen resists tension
-bone adapts to tension and compression by varying props of minerals and collagen fibres
Bone mineralisation
Crystallisation process (Ca, PO4 and others)
-ions from blood plasma deposited in bone tissue
Osteoblasts produce collagen fibres that spiral along length of osteon in alternating directions
Obs also secrete > amounts alkaline phosphatase when active
Ectopic ossification
Abnormal calcification
-may occur in lungs, brain, eyes, muscles, tendons, arteries (arteriosclerosis)
Demineralisation
Dissolving bone
Releasing minerals into blood
Ocs ‘ruffled border’
-H pumps in cell membrane secrete H+ into space between Oc and bone
-Cl- follow by electrical attraction
-HCL pH4 dissolves bone minerals
-acid phophatase (cathepsin) digests collagen
Most of adult skeleton replaced
~every 10 years
Inadequate load and weight bearing will cause
bones to weaken
No load (e.g. space travel)
Rapid bone loss can occur
‘use it or lose it’
Orthodontics PDL
P between PDL & bone
-promotes Ocs
-breakdown bone, restores normal spacing between teeth & bone
Tension on PDL behind movement
-creates Obs
-building new bone to fill gap and restore normal spacing between teeth and bone
Ortho time course
Ocs take ~72 hours to get fully activated
Obs rebuild process takes ~90 days
Stabilising result takes ~10 months
Hormones
Calcitonin - thyroid
Parathyroid hormone (4 glands)
Calcitriol (Vit D) - related to bone
Resorption pits
Howships lacunae
Calcitriol
Intestine - stimulated Ca, PO4 and Mg absorption (calbindin)
Kidney - promotes reabsorption of Ca ions
Oc - promotes activity
Lack of calcitriol
Abnormal softness of bones
- rickets in children
- osteomalacia in adults
PTH
Parathyroid glands found on posterior surface of thyroid gland
PTH released when calcium blood level too low
Essential
Ion imbalance
Changes in phosphate conc have little effect
Change in calcium can be serious –> hypocalcemia, hypercalcemia
Hypocalcaemia
Causes
respiratory alkalosis (hyperventilation)
Symptoms
-excessive excitability of NS –> muscle spasms, tremors or tetany
-Ca normally binds to cell surface contributing to resting membrane potential
-with < Ca, Na channels open more easily
-laryngospasm may cause suffocation
Carpopedal spasm
Hypocalcaemia
- overexcitability of NS
- muscle spasm of hands and feet
Hypercalcaemia
Causes: hyperparathyroidism Symptoms >calcium bone mobilisation -painful softening and fracture > excretion -renal stones -headaches & decreased muscle tone -Na channels less likely to open, depressing NS -near saturation point, ectopic ossification
Osteoporosis
Severe reduction in bone mass Risk factors: -age: women >50, men >60 -gender -size: tall, small frame -smoking -alcohol
Osteopenia
Partial reduction in bone mass
Those at greatest risk of osteoporosis
Postmenopausal white women
< oestrogen > number of Oc progenitors, life span of mature osteoclasts
Other hormones involved in osteoporosis
Inadequate levels of vit D
Thyroid hormone
Cortisol
Gonadal steroids - reduced oestrogen and testosterone promote osteoclastogenesis
Osteoporosis: treatment
Best treatment is prevention
-exercise and calcium intake
-1000mg/day between 25-40
HRT slows bone reabsorption
Bisphosphonates related to pyrophosphate
-inhibiting Oc activity and inducing Oc apoptosis
SERM (selective oestrogen receptor modulator)
Calcitonin administered by injection or as nasal spray
Teriparatide stimulates bone deposition
