Calcium homeostasis Flashcards

1
Q

Why do we need calcium?

A
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)
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2
Q

Calcium functions

A

Communication between neurons
Muscle contraction
Exocytosis
Blood clotting

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3
Q

Calcium pools

A

Intracellular in organelles e.g. SER, mitochondria
Extracellular in blood and lymph
-controlled by intake (GI) and excretion (kidney)
Bone: dynamic, daily turnover

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4
Q

Phosphate

A
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-
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5
Q

Phosphate plasma conc.

A

3.5-4mg/dL

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6
Q

Plasma conc.

A

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
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7
Q

Dietary calcium

A
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
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8
Q

Diet: adult and children requirement

A

Adults: daily intake to overcome losses - GI and kidney
Children: uncontrollable losses, needed for construction of new tissues
Teenagers need most

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9
Q

G.I. tract

A

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

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10
Q

Kidneys

A

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

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11
Q

Summary intake/ losses calcium balance

A

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
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12
Q

Bone composition provides for strength and resilience

A

Minerals resist compression, collagen resists tension

-bone adapts to tension and compression by varying props of minerals and collagen fibres

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13
Q

Bone mineralisation

A

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

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14
Q

Ectopic ossification

A

Abnormal calcification

-may occur in lungs, brain, eyes, muscles, tendons, arteries (arteriosclerosis)

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15
Q

Demineralisation

A

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

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16
Q

Most of adult skeleton replaced

A

~every 10 years

17
Q

Inadequate load and weight bearing will cause

A

bones to weaken

18
Q

No load (e.g. space travel)

A

Rapid bone loss can occur

‘use it or lose it’

19
Q

Orthodontics PDL

A

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

20
Q

Ortho time course

A

Ocs take ~72 hours to get fully activated
Obs rebuild process takes ~90 days
Stabilising result takes ~10 months

21
Q

Hormones

A

Calcitonin - thyroid
Parathyroid hormone (4 glands)
Calcitriol (Vit D) - related to bone

22
Q

Resorption pits

A

Howships lacunae

23
Q

Calcitriol

A

Intestine - stimulated Ca, PO4 and Mg absorption (calbindin)
Kidney - promotes reabsorption of Ca ions
Oc - promotes activity

24
Q

Lack of calcitriol

A

Abnormal softness of bones

  • rickets in children
  • osteomalacia in adults
25
PTH
Parathyroid glands found on posterior surface of thyroid gland PTH released when calcium blood level too low Essential
26
Ion imbalance
Changes in phosphate conc have little effect | Change in calcium can be serious --> hypocalcemia, hypercalcemia
27
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
28
Carpopedal spasm
Hypocalcaemia - overexcitability of NS - muscle spasm of hands and feet
29
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 ```
30
Osteoporosis
``` Severe reduction in bone mass Risk factors: -age: women >50, men >60 -gender -size: tall, small frame -smoking -alcohol ```
31
Osteopenia
Partial reduction in bone mass
32
Those at greatest risk of osteoporosis
Postmenopausal white women | < oestrogen > number of Oc progenitors, life span of mature osteoclasts
33
Other hormones involved in osteoporosis
Inadequate levels of vit D Thyroid hormone Cortisol Gonadal steroids - reduced oestrogen and testosterone promote osteoclastogenesis
34
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