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ENDO > ENDO Week 7 > Flashcards

ENDO Week 7 Flashcards

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1
Q

what are some functions of calcium in ecf?

A

-synaptic transmission
-nerve excitability
-muscle contraction
-blood coagulation

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2
Q

what are some functions of calcium in icf?

A

-muscle contraction
-second messenger

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3
Q

what is the structure and location of the parathyroid gland

A

-four small glands
-location behind the thyroid gland

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4
Q

what kind of hormone is PTH and what is it secreted by

A

peptide hormone
chief cells of parathyroid gland

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5
Q

what pathway does PTH use and where are its target cells

A

G protein coupled receptor
target cell: bone and kidney

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6
Q

what is PTH biosynthesis

A

-prepro, cleaved in rough ER, cleaved to
-pro, cleaved in Golgi complex to
-active PTH

PTH is preformed readily available, stored in vesicles of chief cells

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7
Q

describe ionized, protein bound and complex calcium

A

ionized
-diffusible through membrane
-biologically active

protein bound
-not diffusible
-in circulation
-90% albumin, 10% globulin

complex calcium (active)
-ex: calcium phosphate

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8
Q

what tissues are involved in maintaining calcium homeostasis

A

bone, intestine and kidney

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9
Q

what are the hormones involved in calcium regulation/homeostasis

A

PTH, calcitonin and vitamin D

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10
Q

what are the cell types involved in calcium homeostasis

A

osteoblasts, osteocytes, osteoclasts

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11
Q

how does the intestine regulate calcium and where does it occur in the intestine

A

intestinal absorption is dependent on vitamin D and occurs in the duodenum and proximal jejunum

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12
Q

how does the kidney regulate calcium

A

renal tubular reabsorption
- kidneys reclaim substances from the filtrate (the fluid that has been filtered from the blood) back into the bloodstream, preventing their loss in urine

excretion
-through urine

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13
Q

how does bone regulate calcium

A

bone remodelling: exchange between plasma and bone

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14
Q

what is plasma calcium homeostasis dependant on?

A

 Calcium intake
 Hypocalcaemic effects of calcitonin
 hypercalcaemic effects of PTH and vitamin D

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15
Q

what does decreased blood calcium cause?

A

increased vitamin D and PTH

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16
Q

what is the action of PTH on bone and where are there receptors located

A
  • bone resorptive effect (breakdown of bone to release calcium to bloodstream)
  • removes calcium and phosphate from bone
  • receptors located on osteoblasts
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17
Q

what does the binding of PTH on osteoblasts trigger

A

triggers synthesis of RANKL in osteoblasts that increase number and activity of osteoclasts

RANKL (in osteoblasts) binds to RANK (in osteoclast precursors) and produces functioning osteoclasts

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18
Q

what is the rapid phase of the effect of PTH on bone

A

PTH binds to receptors on osteocytes making them pump calcium from bone, increasing blood calcium levels rapidly.

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19
Q

what is the slower phase of the effect of PTH on bone

A

increase activity of osteoclasts

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20
Q

what is PTH action on intestine

A

-indirect action
- acts synergistically with vitamin D to absorb calcium and phosphate

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21
Q

how is PTH affect on absorption of calcium in intestine indirect

A

PTH stimulates the production of active vitamin D (calcitriol) in the kidneys. Calcitriol then promotes calcium absorption in the small intestine)

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22
Q

what is PTH on kidney and where does it occur

A
  • increased calcium reabsorption, occurs in late distal tubules
  • decreased tubular phosphate reabsorption
    (increased phosphate excretion)
  • stimulates vitamin D3 synthesis to 1,25-dihydroxyvitamin D3 (calcitriol)
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23
Q

how is PTH secretion regulated

A

-low calcium stimulates PTH

-high calcium decreases PTH (by calcium binding to calcium sensing receptor CaSR (a GPCR) in parathyroid)

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24
Q

what can a persistent decrease of PTH cause

A

PT to shrink

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25
what is the net effect of PTH
increased blood calcium decreased blood phosphate
26
what kind of hormone is calcitonin and where is it secreted from
protein hormone secreted from parafollicular or s from thyroid
27
what is the relationship between calcitonin and PTH
antagonistic action calcitonin has a hypocalcemia effect
28
when and how is calcitonin secreted
stored in secretory vesicles in C cells, released when increased calcium
29
calcitonin action in bone
-decreases bone resorption -decreased bone calcium and phosphate release
30
calcitonin action in kidney
-decrease calcium and phosphate reabsorption (increase excretion of calcium and phosphate)
31
calcitonin action in intestine
decreased calcium absorption
32
what are the target cells of calcitonin and what does it do
osteoclasts - decreases osteoclast formation -increased deposition of calcium in bone to lower calcium in blood
33
what is calcitonin used to treat
Paget disease
34
what is the net effect of calcitonin
decreased plasma calcium decreased plasma phosphate
35
what kind of hormone is vitamin d and what is it synthesized from
a sterol hormone; synthesized from cholesterol
36
is vitamin d fat or water soluble
fat soluble
37
what is vitamin d's biologically active form and where is it produced
Calcitriol or 1, 25 dihydroxycholecalciferol - produced in the kidneys
38
why is vitamin d important
crucial for calcium absorption and bone health
39
how is 1, 25 dihydroxycholecalciferol synthesized
7- dehydrocholesterol + sunlight --> previtamin D3 --> Cholecalciferol (Vitamin D3) --> 25 -Hydroxycholecalciferol (converted in liver) --> 1,25- Dihydroxycholecalciferol (converted in proximal tubule)
40
what enzyme does PTH stimulate in the kidney to make calcitriol
1 alpha hydroxylase*** is the enzyme which PTH stimulates in the kidney to make calcitriol (last step 25-hydroxycholecalciferol to calcitriol)
41
what hormone is required for the formation of 1, 25 dihydroxycholecalciferol
PTH
42
what is 1, 25 dihydroxycholecalciferol/calcitrol biosythesis
 Starts in skin  conversion occurs in liver Active hormone synthesized in the kidney, PTH activates synthesis of vit d in kidney
43
what class of hormone is vitamin d similar and how
similar to steroid hormones in terms of structure and mechanism of action
44
how does PTH and calcium affect Vitamin D synthesis
increased PTH --> increased vitamin D synthesis increased calcium --> decreased vitamin D synthesis
45
how does vitamin D affect PTH synthesis
increased vitamin D --> decreased PTH synthesis
46
action of vitamin D on bone
vit d acts synergistically with PTH to cause demineralization and bone resorption via osteoclastic activity
47
action of vitamin D in intestine
increases calcium absorption increases phosphate absorption
48
action of vitamin D in kidney
- increased calcium reabsorption - increased phosphate reabsorption
49
vitamin D net effect
increased plasma calcium increased plasma phosphate
50
what does bone remodelling mean
removal of old bone (resorption) and formation of new bone
51
what cells are involved in bone remodelling and their responsibilities
 Osteocytes = bone cells  Osteoblasts = bone forming  Osteoclasts = bone resorption
52
what are the effects of PTH and vitamin D on bone
increased bone resorption
53
what are the effects of calcitonin on bone
decreased bone resorption
54
what factors increase bone formation
- low PTH or intermittent increase in PTH --> facilitates osteoblast proliferation --> increased bone formation - low concentration of vitamin D --> increased bone formation
55
what factors increase bone resorption
high concentration of vitamin d and PTH --> increases bone resorption
56
how does increased blood calcium lead to decreased PTH
increased blood calcium--> calcium binds to CaSR --> activation of G signalling pathway in parathyroid chief cells --> decreased synthesis and release of PTH
57
what are some other hormones that effect calcium homeostasis
increased cortisol= increased bone resorption increased estrogen=decreased bone resorption decreased estrogen = increased osteoclastic activity --> osteoperosis
58
how does hypoparathyroidism cause increased neuronal excitability
decrease PTH --> decreased bone resorption --> decreased blood calcium --> increase neuronal excitability
59
what are titanic muscle contractions and what are they caused by
caused by hypoparathyroidism - rapid, continuous stimulation of motor neurons
60
what is tetany in the hand
carpopedal spasm
61
how is tetany caused
decreased PTH --> hypocalcemia --> increased excitability of the nerve and muscle --> tetany
62
how does hypoparathyroidism effect and ECG
prolonged QT interval
63
what is twitching of facial muscle (caused by hypoparathyroidism)
Chrostek’s sign
64
what is psuedohypoparathyroidism
rare familial disorder Target organs are resistant to PTH non-functioning PTH receptor - defect in G protein of PTH receptor
65
what does pseudohypoparathyroidism cause
low serum calcium levels defects in bone growth plasma calcium is low plasma phosphate is high
66
what is hypo and hypercalcemia effect on nerve excitability
hypocalcemia=increased excitability hypercalcemia=decreased excitability
67
what is primary hyperparathyroidism caused by and its effects
 Caused by adenoma tumour  Increases PTH secretion  Increases blood calcium  Decalcification of bone (bone resorption)  Causes renal stones
68
what is secondary hyperparathyroidism caused by and its effect
 Compensatory response to hypocalcaemia*  Increases PTH secretion
69
what can renal failure cause
Renal failure induced decreased vitamin D will reduce blood calcium and cause secondary hyperparathyroidism
70
does primary and secondary hyperparathyroidism related to its gland axis?
No
71
what form of calcium is filtered in the kidney
only ionic and complex form is filtered (active form)
72
what percent of filtered calcium reabsorbed and where does this reabsorption take place
99% of filtered calcium is reabsorbed  60% reabsorption takes place in the proximal convoluted tubule (PCT) - No hormone required  40% reabsorption takes place in the TAL (thick ascending limb) and DCT (distal convoluted tubule) - Hormone dependent
73
what happens to the remaining calcium
1% of calcium is excreted in urine
74
how does lactation affect calcium balance for the mother
o Rapid and transient demineralization of maternal skeleton mediated by parathyroid hormone o Lactation → considerable stress on maternal calcium homeostasis
75
how does increased plasma calcium decrease PTH secretion
Increase calcium activates calcium sensors (CaSR) on parathyroid cells --> GPCR (activates phospholipase C --> generates IP3 and DAG) --> results in calcium release from internal stores
76
The active form of calcium that helps in blood coagulation is
ionized calcium
77
Hypocalcemic hyperexcitability in the nerves is due to
Increased permeability to sodium ions

ENDO (8 decks)

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