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Week 8 Calcium Flashcards

1
Q

Intracellular Ca2+ concentration and function

A

very low concentration (1microM)
reversible increase of Ca2+ can bind proteins -> cell processes

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2
Q

Extracellular Ca2+ concentration and function

A

High concentration (1mM)
1. bone mineralisation
2. maintain activity of excitable tissue

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3
Q

2 main types of Calcium in plasma

A
  1. ionised Ca2+ (free)
  2. albumin-bound Ca2+ (inactive)
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4
Q

which type of calcium is actively regulated

A

ionised calcium:
Its concentration is constant

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5
Q

which organs contribute to calcium balance

A

GI, Kidney, Bone

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6
Q

negative calcium balance leads to….

A

decrease in bone density

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7
Q

osteocytes

A

mechanosensor cells for bones
stimulates bone growth
may become osteoblasts

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8
Q

osteoclasts

A

bone resorption

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9
Q

osteoblasts

A

make bone

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10
Q

osteoblast - bone formation process - osteoid (bone matrix)

A
  1. osteoblast precursor
  2. osteoblast
  3. osteoid
  4. calcified osteoid
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11
Q

how long does it take for osteoid to mineralise

A

several days

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12
Q

how long for full mineralisation

A

several months

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13
Q

mineralisation main component

A

hydroxyapatite(calcium phosphate)

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14
Q

what is hydroxyapatite

A

calcium phosphate (& OH)
tiny crystals around collagen fibres, provides rigidity

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15
Q

what does mineralisation depend on?

A

calcitriol (active form of Vitamin D)

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16
Q

calcitriol deficiency leads to??

A

osteomalacia
rickets (kids)

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17
Q

alkaline phosphate (ALP) and mineralisation

A

An enzyme expressed by osteoblasts:
1. hydrolysis and releases inorganic phosphate ions
2. hydrolyses pyrophosphate (2 phosphate - inhibitor of mineralisation

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18
Q

osteoclast and bone resorption

A

multinucleate:
border adjacent to bone releases H+ and enzymes
enzyme:
carbonic anhydrase II, H+ generation.

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19
Q

which cells have RANK ligand

A

bone marrow stromal cells

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20
Q

which cells have RANK (receptor)

A

precursor osteoclasts

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21
Q

Characteristics of osteopetrosis

A

Increased bone density/mass
Increased fragility due to brittle structure.

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22
Q

cause of osteopetrosis

A

failure of matrix degradation by osteoclasts.

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23
Q

most common cause of osteoporosis

A

oestrogen drop after menopause

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24
Q

main cause of osteoporosis

A

increased bone resorption

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25
what is Paget's disease
overactive osteoclasts
26
calcitriol comes from?
steroid hormone -> from vitamin D
27
what does PTH regulate/how fast
-regulate ionised calcium levels -minute-by-minute increased in response to falling Ca2+
28
what controls PTH secretion
calcium receptors on cell -> senses calcium concentration
29
what receptor is the calcium receptor
G protein coupled receptors
30
PTH biochemical effects and what organs:
1. **calcium efflux from bone** 2. **Ca2+ reabsorption** (distal) 3. **bicarbonate** and **phosphate loss** (proximal) 4. **Ca2+ absorption** (intestinal)
31
what stimulates/suppresses PTH system
(urinary calcium loss, decreased bone resorption, decreased calcitriol) will stimulate PTH release -> to reverse this action.
32
principal function of calcitonin
to reduce osteoclast activity, treat high serum calcium.
33
calcitonin as a biomarker(where is it secreted)
Secreted from **thyroid gland**: 1. medullary cancer of the thyroid 2. will **increase** when serum Ca2+ **increases**
34
cholecalciferol (Vitamin D) to calcitriol production pathway
1. Has a precursor on skin, converted through sunlight UV 2. cholecalciferol is converted to calcitriol in the **liver** and **kidney**
35
calcitriol synthesis pathway
1. 25 hydroxylase adds OH to cholecalciferol (***Liver***) 2. 25-OH vitamin D functions **constitutively** 3. 1alpha-hydroxylse adds another OH to 25-OH vit D. (***Kidney***) 4. 1,25 (OH)2 vitamin D is **stimulated by PTH**, calcium can affect its activity.
36
calcitriol effect, and affect what organs
Maintain calcium and phosphate levels: *By itself*: - **increase Ca2+ and PO4-** absorption (GI) *with PTH*: - Increases **bone resorption** and stimulate osteoclast (RANKL). - Increases renal **Ca2+ reabsorption**.
37
difference between calcitriol (VitD) and PTH
PTH leads to phosphate loss (renal - proximal tubule) Calcitriol leads to phosphate increase (GI absorption) PTH is short term, calcitriol is long term Ca2+ regulation.
38
how does PTH affect calcitriol
PTH stimulates 1alpha hydroxylase
39
how does calcitriol affect PTH
**calcitriol deficiency** -> impaired PTH signalling calcitriol can **switch off PTH gene transcription** via vitamin D receptor.
40
how does calcitriol promote its own inactivation
activates 24 hydroxylase
41
hypercalcaemia clinical manifestations
stones: renal stones bones muscle weakness: competition with inward Na+ flux. abdominal moans: pain psychic groans: depression...
42
non-pathological hypercalcaemia
Due to high plasma albumin -> raised calcium: 1. dehydration 2. intravenous injection albumin 3. venous stasis
43
Primary hyperparathyroidism causes
(90%) solitary adenoma hyperplasia (rare) carcinoma
44
Secondary hyperparathyroidism cause
PTH increase due to low calcium. (appropriate)
45
Tertiary hyperparathyroidism causes
Results from chronic secondary hyperparathyroidism: secondary gland becomes overactive
46
1y hyperparathyroidism biochemistry
Increased calcium, Increased PTH Low bicarbonate and phosphate normal ALP moderately elevated ALP when severe
47
treatment of 1y hyperparathyroidism
Immediate - treat high calcium: 1. rehydration 2. drugs Definitive: Remove of adenoma
48
imaging of hypercalcaemia
renal stones
49
treatment of hypercalcaemia
1. calcitonin - **reduce osteoclast** activity 2. **bisphosphonates** - inhibits bone resorption and osteoclast activity. 2. furosemide - **diuretic**, inhibit Ca2+ reabsorption 3. glucocorticoid: **prolong calcitonin** effect
50
why are hypercalcaemias common in malignancies
1. Metastasis deposit on bone and directly activate osteoclasts 2. release endocrine factors that act on bone
51
what disease affects calcitriol levels
Hodgkin's lymphoma and Sarcoidosis Has 1 hydroxylase activity, so it will contribute to calcitriol synthesis.
52
solid tumours and endocrine factors
some solid tumours secrete **PTH-related peptide** but PTHrP is difference from PTH, **PTH level is also suppressed**.
53
name when PTHrP is the cause of hypercalcaemia
humoral hypercalcaemia of malignancy
54
metastatic breast tumour and hypercalcaemia
locally produce PTHrP
55
multiple myeloma and hypercalcaemia
activate osteoclasts through cytokines like RANKL
56
Malignancy biochemistry diagnosis - hypercalcaemia
Raised calcium & ALP High phosphate Low PTH
57
Hypercalcaemia - malignancy vs adenoma - biochemistry
Adenoma will have **high PTH**, low phosphate Malignancy will have **low PTH**, high phosphate. **Adenomas rarely have elevated ALP** due to a modest **bone turnover**. Whereas **malignancy may have very high ALP** due to a much less controlled bone turnover.
58
sarcoidosis and hypercalcaemia
has 1hydroxylase activity, synthesise calcitriol, high calcium, **normal PTH**.
59
familial hypocalciuric hypercalcaemia (FHH)
Ca2+ sensing **receptors are less sensitive**. PTH and Ca2+ have a **higher set point** now. elevated PTH and Ca2+ in blood. Low urine calcium (excretion) is due to PTH elevation.
60
factitious hypocalcaemia
low albumin, less calcium: 1. **nephrotic** syndrome 2. liver disease, **less protein synthesis** 3. **malnutrition**
61
causes of low 1,25 vitamin D
1. malabsorption 2. inadequate sunlight 3. diet factors 4. chronic renal disease rarely enzyme issues
62
what does calcitriol deficiency lead to (steps)
1. low calcium 2. high **PTH** (2ndary hyperp) 3. low phosphate 4. high bone resorption 5. high **ALP**
63
osteomalacia and calcitriol
low calcitriol meaning that osteoid cannot be calcified properly
64
inherited causes of osteomalacia
1. deficient 1 hydroxylase (low calcitriol) 2. low ALP 3. low phosphate 4. defective calcitriol receptor
65
causes of hypoparathyroidism
1. surgical damage or removal of parathyroid. 2. suppressed secretion (maternal hypercalcaemia)
66
hypocalcaemia biochemical effects
low Ca2+ and low PTH. Phosphate may be elevated
67
treatment of hypocalcaemia
doses of **calcium** and **vitamin D** or **calcitriol**
68
(aging) osteoporosis vs osteomalacia
osteoporosis has a normal histology (less bone density) and relatively normal biochemistry. **osteomalacia** has an **abnormal histology and biochemistry**
69

CBE (16 decks)

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