L8 Parathyroid and calcium regulation Flashcards
0
Q
What are the cells in parathyroid glands actively releasing parathyroid hormones?
A
- Chief cells
1
Q
What is the function of parathyroid glands?
A
- to regulate calcium level in blood at a very narrow range
2
Q
How are chief cells regulated?
A
- regulated by serum calcium and vitamin D
- parathyroid hormones are secreted in response to hypocalcaemia
- it can be continuously secreted
- secretion requires Mg ions in blood
3
Q
What is parathyroid hormone?
A
- it is a made as 110 AA precursor and being processed in ER to 84 AA precursor
- removal of single NH2 terminal AA reoves 90% of bioactivity (its activity is based on number of NH2 terminals)
- serum half life is 20 mins
- rapidly inactivated in liver and kidney
- normal range= 10-60 pg/ml
4
Q
What are the functions of parathyroid hormones?
A
- parathyroid glands monitor calcium level in blood (chief cells have sensors)
- when blood calcium level is low, the parathyroid glands make more PTH
- increased in PTH causes the body to put more calcium into blood
- PTH acts as negative feedback to reduce level of calcium in blood
- release of calcium in blood is by bone erosion and absorption of blood calcium is done by kidneys
5
Q
What are the roles of calcium? (7)
A
1) exocytosis at synaptic transmission & hormone release
2) bone formation & maintenance
3) muscle contraction, including cardiac muscles
4) primary role in blood coagulation (cofactor in conversion of prothrombin to thrombin)
5) enzyme regulation
6) contributes to electrical properties of membrane
7) reduction in ionised calcium increases NA permeability & enhances excitability of excitable tissues
6
Q
Where are the main source of calcium come from?
A
- 99%= skeletal (from hydroxyapatite); 1%= extracelluar ; 0.1%= intracellular
7
Q
What are the 2 states of calcium found in blood?
A
- ionised (50%) and bound (50%)
- 35-40% is bound by plasma protein and 10-15% is bound by complexed with anions
8
Q
What do calcium ions bind to in serum?
A
- binds to carboxyl groups of albumin and the binding is highly pH dependent as calcium competes with H+
- acute acidosis (more H+ in blood= competes with Ca for albumin) decreases binding and increases ionised calcium ( does not alter the total level of calcium so has to measure the ionised calcium level to see this effect)
- acute alkalosis occurs when there is an increase in protein binding to calcium
9
Q
What would happen if it is hypocalcaemia?
A
- increases membrane permeability to NA+, resulting in hyperactivity of axons
- tetany
10
Q
What would happen if hypercalcaemia occurs?
A
- high level of calcium causes a decrease membrane permeability to Na+ so axons become more difficult to depolarise
- calcium can deposit in soft tissues = painful and can lead to failure
11
Q
What is the normal serum calcium range?
A
- 2.2-2.6 mmol/L
- for non-pregnant adults, there should be no daily gain/loss of calcium, magnesium or phosphate = zero calcium balance
12
Q
What is the calcium level in ECF and ICF?
A
- ECF contains 10 to the power of -3 M; ICF contains 10 to the power of -6M of calcium
- 90 -99% calcium found in mitochondria bound to phosphate
13
Q
How is low cytosol calcium level (in ICF) achieved?
A
- it is being maintained by 3 pump transport systems: in plasma membrane, in inner mitochondrial membrane and in microsomal membranes (eg sarcoplasmic reticulum)
- calcium diffuses across these 3 membranes into cytosol
14
Q
What individuals would have a mineral homeostasis in positive balance?
A
- growing child
15
Q
What individuals would have a mineral homeostasis in a negative balance?
A
- immobilised patients= lose bone
16
Q
What organs are involved in calcium regulation?
A
- intake in gut; output in kidney ; storage in bones
17
Q
What hormones are needed for Calcium homeostasis?
A
- PTH, calcitonin and vitamin D
* precisely controlled (within 3% in humans)
18
Q
What actions do PTH bring?
A
- efflux of calcium from bone; increases uptake of calcium in blood and reduces loss of calcium in kidneys
- calcium can activates the inactivated form of vitamin D in kidneys so the active vitamin D can have effects in guts and further increases absorption of vitamin D
19
Q
What is the action of PTH on bones?
A
- releases calcium from rapidly turning over calcium pool from surface of bone and several hours later, releases calcium from slowly turning over pool in bone
- calcium release is accompanied by release of matrix degradation products and phosphate
- when there is a continually high does of PTH present, acute effect on osteoblasts, ie. reduce mineralisation then inhibit formation ( DIRECT EFFECTS as osteoblasts contain PTH receptors); chronic effect on osteoclasts, ie stimulate bone resorption by increasing number of osteoclasts ( INDIRECT effect due to osteoclasts do not have PTH receptors)
20
Q
What is the action of PTH on bone cells?
A
- PTH binds to PTH receptors on osteoblasts and RANKL is attached on osteoblasts ( some RANKL is masked by osteoprotegrin)
- RANKL is recognised by osteoclast precursors by using RANK receptors on them so osteoclast precursors become matured and enlarged
- osteoprotegerin can mask RANKL so osteoclast precursors can no longer bind to RANKL so no maturation
- the balance between RANKL and osteoprotegerin is important to achieve balance in bone absorption and formation
- increase level of PTH = more interaction between osteoblasts and osteoclasts
21
Q
What are the actions of PTH on KIDNEYS?
A
- direct effects: increases Ca reabsorption so fewer calcium ions lost and inhibit phosphate reabsorption in tubules
- increases production of 1,25 dihydroxycalciferol increases the enzyme activity (which is needed for conversion)
- so the active from of vitamin can induce effects on guts
22
Q
What are the actions of PTH on guts?
A
- produces indirect effects: enhances calcium absorption via 1-25,dihydroxycalciferol and calcium binding proteins
- very slow, takes more than 24 hours to act
23
Q
What is calcitonin?
A
- it is a 32 AA peptide hormone secreted by thyroid gland parafollicular C cells, from other cells in parathyroid, adrenal medulla and thymus
- they are ultimobranchial cells (embryonic structure that gives rise to parathyroid producing cells)
- normal basal serum level = s degraded in kidney and liver
24
When is calcitonin secreted?
- when it is hypercalcaemia, it lowers serum calcium level and inhibits bone resorption
- it is used as a treatment for osteoporosis, Pagets disease (where osteoclast break down bone more quickly than osteoblast)
25
What are the actions of calcitonin on BONE?
- produce major effects: reduces bone resorption and take effect within minutes of administration. Acts on osteoclasts (have receptors for calcitonin)
26
What are the actions of calcitonin on GUT?
- no effect
27
What are the actions of calcitonin on KIDNEYS?
- decreases reabsorption of calcium and phosphate
28
What are the actions of calcitonin on other body parts? (4)
- anti-hypertensive
- ani-inflammatory
- promote fracture healing
- promote wound healing
29
What is vitamin D?
- a steroid hormone that binds to nuclear receptors on cells so have direct effects on DNA and RNA synthesis
- small in size and it is lipid soluble
30
What are the main sources of vitamin D?
1) intestinal absorption from diet: foods with ergocalciferol is absorbed with fats ( impaired fat absorption= impairs D2 uptake)
2) dermal production: photoconversion of 7-dehydro cholesterol to cholecalciferol in skin
31
How is vitamin D being metabolised?
- vitamin D usually presents in an inactive form and has to be converted (takes 12-24 hours)
- has to undergo 25-hydroxylation in liver and 1-hydroxylation in kidney to form 1,25-hydroxycalciferol (ACTIVE FORM)
(can INACTIVATE by 24-hydroxylation)
* majority source of 1-hydroxylase is from kidneys to achieve 1-hydroxylation (minor source= bone; placenta)
half life of vitamin D is between 1-6 weeks
32
What are the actions of vitamin D?
- increases serum calcium and phosphate level
- acts primarily on gut (after activated in kidneys)
- acts secondarily on bones
- it can reduce secretion of PTH
33
What are the actions of vitamin D on BONES?
- powerful stimulant of bone resorption
| - has to presence in order to achieve a maximum response to PTH
34
What are the actions of vitamin D on GUT?
- increases calcium and phosphate absorption
- enhances alkaline phosphatase production and production of calcium binding proteins
- anephric (no kidneys) patients cannot convert 25-hydroxycalciferol into 1,25-dihydroxycalciferol (as the reaction takes place in kidney!)
35
What would vitamin D deficiency lead to?
- hypomineralisation
| - impaired skeletal growth, eg rickets
36
What are the consequences of primary hyperparathyrodisim? ( caused by a parathyroid adenoma or general hyperplasia)
- leads to distribution of calcium ions in soft tissues, e.g renal calculi, tissue calcification, fragile bones
* treat with calcitonin or surgery
37
What are the consequences of hypoparathyroidsim?
- usually it is an autoimmune disorder
- leads to low calcium level and causes tetany (due to hyperactivated axons)
* Treat with diet supplements or PTH
38
What are secondary hyperparathyrodism?
- occurs in renal diseases or vitamin D deficiency
