Mineral Homeostasis Flashcards
activation of amino acid based hormones
through acitvation of cyclic AMP and cGMP with G-protein receptors and activating PROTEIN KINASE A
through PIP second messenger - uses phospholipase c and more rapid on/off responses
Protein kinase C
activation of steroid hormones
direct gene activation mechanism
- may take longer for effects to be seen but can LAST LONGER
- crosses membrane and gets into cell and to the nucleus for transcription of genes
phosphodiesterase
breaks down cAMP and cGMP
5 - types
type 5 phosphodiesterase
target for drugs for asthma, obstructive pulmonary disease, heart failure, and erectile dysfunction
what can inhibit phosphodiesterase
caffeine
what is the only thing PTH responds to
decrease in calcium
so released in response to low plasma Ca++
expanded epiphyseal growth plate
seen in rickets
rickets symptoms
deficient grwoth in long bones
chronic hypocalcemia
expanded epiphyseal growth plate
bowing of legs
primary action of vitamin D
increases Ca++ absorption by intestine
PERMISSIVE FACTOR WITH PTH
T/F if vitamin D deficient - you wont respond to PTH
TRUE
PTH works as a control factor for what
enzyme in the kidney
enzyme produces the 1-25 dihydroxy vit D and PTH stimulates this enzyme
will excessive vit D lead to higher levels of 1-25 dihydroxy metabolite?
NO
- but will see an increase in the precursor that is produced at the liver (25 hydroxy)
sudden drop in Ca++ results in
tetany of skeletal muscles
normal Ca++ level in the plasma
10mg/100ml normal plasma Ca++
possible sources of Calcium
diet supplement or from skeletal source
hypercalcemia
describe
when is it a problem
short term vs. long term
Problem on chronic, not acute level. so becomes a problem when there is long term high calcium levels and can get soft tissue calcification in heart/cardiac valves and kidney tubules
can see lethargy, digestive tract abnormalities, possible cardiac arrhythmia’s
what happens in calcitonin gene knockout in mice?
increased bone mineral content in these mice
pro-calcitonin implications if present
marker for sepsis
describe calcitonin
single chain polypeptide of 32 amino acids
secreted by the parafollicular cells of the thyroid and present in all vertebrate classes
normal function is UNKNOWN
when given intramembranous invusion of calcitonin
hypocalcemic
- calcium will be deposited into the bone - treatment method in osteoporosis?
calcitonin actions
hypocalcemic in mammals
no effect in other classes
secreted in response to high plasma Ca++, so causes Ca++ depositon in bone
high calcitonin or no calcitonin?
high - meduallry carcinoma of the thyroid or low due to thyroid removal - BONE AND CALCIUM METABOLSIM SEEM TO BE NORMAL
what does calcitonin inhibit?
release of sphingosine-1-phosphate from osteoclasts
cholecalficerol is also called…
Vit D3 - this is the type that is in supplements
sources of vitamin D
sunlight exposure - through skin
or ingesting it as a supplement
vitamin D from sun reaction
7-dehydrocholesterol converted to cholecalciferol (vit d3) in skin
does cholecalciderol have biological activity?
no
toxicity of Vit D?
starting to lean away from this and say not really
deficient in 1-alpha hydroxylase?
genetic deficiency in this enzyme causes rickets unresponsiveness to vit D but responds to exogenous calcitriol (vit d 1,25 version)
because cannot metabolize the vitamin d
so these individuals can resume normal growth when given the medication of exogenous calcitriol
systemic growth factors
growth hormone and thyroid hormone
thyroid hormone deficiency?
can lead to a syndrome known as cretinism
even if growth hormone is present - thyroid hormone is needed for it to elicit its effects and the child will have stunted growth and mental cognitive dysfunctions as well
IGF-1 stimulation
stimulated by growth hormone
so growth hormone stimulates IGF-1 from the liver
laron dwarfism
lack of GH receptors or mutations in IGF-1 receptor so even if have GH - these individuals cannot respond to it
-no treatments right now
- in comparison to children who have a lack of GH - if treated can resume ‘normal’ growth
excess GH in adults and children
adults - acromegaly and adults DO NOT INCREASE IN HEIGHT
children - gigantism
control of GH
both stimulatory and inhibitory at level of the hypothalamus
what type is PTH in terms of treatment for osteoperosis?
OSTEOANABOLIC
- stimualtes bone growth
- decreases the frequency / rate of fractures
GIVEN IN PULSES
Osteoantiresorptive agents
treatment method for osteoporosis but these DO NOT decrease/change the fracture rate - they just INHIBIT THE RESORPTION PROCESS
BISPHOSPHONATES
CALCITONIN
ESTROGENS
osteoclast activating factor is…
an inflammatory mediator (interleukin) and is a potent stimulator of bone resorption
effects of increased IL-1 and IL-6
why do they increase
increased bone resoprtion
due to the loss of inhibition by estrogen (post menopausale osteoporosis)
role of estrogen
inhibits inflammatory mediator syntehsis
without estrogen inhibiting - IL-1 and IL-6 will increase and causes increased bone resorption
what are osteoblasts role in osteoporosis?
they can produce Il-1 and IL-6 and TNF -alpha
do osteoclasts have PTH receptors?
NO
what controls the differentiation of osteoclasts?
osteoblasts mediate this
high PTH results in increased osteoclasts but effect is mediated through the osteoblasts
where is RANK-L and RANK
RANK-L is produced by osteoblasts and RANK is on the membrane of osteoclast pre cursor cells
what does binding of RANKl and RANK do?
this binding stimulates differentiation of osteoclasts
Osteoprotegrin
OPG
