Calcium & Calcitrophic Hormones Flashcards
briefly, what is the calcium concentration inside and outside the cells how does it stay that way
3 ways calcium exists in the plasma
Calcium concentration outside: HIGH
calcium concentration insdie: LOW
remains low like this inside cells through a Ca+ pump in the ER, which sequester calcium inside teh ER via using ATP
remains high outside and low inside: because calcium constantly pumped out while H+ pumped into the cell (using ATP) & cacium out and Na+ in exchanger
Calcium in the plasma
- ionized form: (Ca2+) used for APs, motlitiy, contraction, etc. majority in ionized
- protein-bound: to globulin and albumin (for it to not be broken down quickly) lots here too
- complexed: with other moelcules (like phosphate, biacarb, etc.)
(increase amount of calciumbound to phosphate –> less ionized calicum to be used)
how does the body take in and use calcium and phosphate
Calcium
- the action of VitD allows for calcium to be taken in through the diet
- absorbed into the body; used (99%) in the bones for remodeling
- urinary excretion or fecal excretion
Phosphate
- 2/3rds of taken in phosphate and absorbed and go to muscle mass for storage, or to the bone
- excerete via feces, or excreted through kidneys (majority) hence with CKD: this cannot occur
Bones
- cortical v tabecular bone
- resorbtion v formation
- osteoblast v clast
Cortical bone: hard outside, making 80% of bone mass, but less metabolically active
Trabecular bone: 20% of mass; but 5x surface areas of cortical & metabolically active main site of calium turnover
Resorbtion: bone breakdown
formation: bone making
formation until 20s
peak bone mass at 25-35
bone resorbtion 40+
Osteoblasts: bone builders
- secrete collagen and form osteoid
- have PTH and vitD receptors
- regulate clast activity
Osteoclasts: breakdown the bone
- macrophage like activity
- excress calcitonin and PTH receptors
Osteocytes: the blasts which get calcified from the matrix they form, so theyre the connection between bone surfaces to one another : through canaliculi (tunnels)
- mild clast activity
The Process of Bone Formation & Resorbtion
Formation
- Blasts are recruited
- they synthesize collagen fibrillar matrix, osteoid = scaffold for calcium phosphate deposits
- hydroxide and bicarb add to calcium phosphate = hydroxapatie and mineralization of osteoid
- the osteocytes are connected to each other via canaliculi: allows transfers bone from interior to exteroid
Resorbtion
- osteoclasts singaled by osteoblasts
- clasts attach to bone
- they dissolve via lysosomal enzymes, collagenase, phopahtase and release phospahte and calcium
- macrophages clean up excess
- blasts are recruted to fill in
Vitamin D synthesis
7-dehydroxycholesterol converted to inactive Vit D (cholecalciferol/ergocalciferol)
this goes to the liver
converted to cacidiol
calcidiol goes to the kidney: through the action of 1 alpha hydroxylase becomes active Vit D3 (calcitriol)
active Vit D = 1, 25 OH vitD3
measured in the blood = calidiol 25(OH)D (the one which comes from the liver conversion)
The process of Vit D prodcution is regulated
- in times of low active Vit D, low Calcium and low phosphate, triggered Vit D production
- in times of enough calcium and phosphate, the breakdown of active to inactive via 24-hydroxylase is active
Vit D Receptors
where are they
what are they more affinity form
Receptors for Vit D are intracellular: since Vit D is fat soluable
Affinity: more affinity for active Vit D than inactive ; even though there is more inactive VIt D circualting than Vit D
Vit D receptor = VDR
when bound,
- increased calbinding aka more calcium uptake at SI brush boarder
- bound to osteoblasts: increase syntehsis and recruiting clasts
- bidning on the PTH gene supressed the PTH (decreased about of PTH)
The role of VIt D
- increase plasma Calcium and phosphate
- increase reabsorbtion of calcium and phosphate via kidneys
- increase calcium reabsorbtion in GI
Parathyroid hormone
- type of homrone
- what does it trigger
- where does it act
PTH = parathyroid hormone
- water-soluable hormone produced by the chief cells on parathyroid glands
- released in a pulsitile function
- PTH will regulate the level of calcium in the serum: low levels of serum calcium will trigger PTH action
- when calcium is high, calicum binds and turns off the PTH hormone so that it cant elicit its effects
Actions
- osteoblasts: increase proliferation, decrease collagen syntehsis
- osteoclasts: increase resorbtion and proliferation: released more CA+ from the bones
- increase calcium reabsorbtion in the distal tubule
- decrease phosphate reabsorbtion: let it go: to decrease amount able to bind to calcium
Role of calcitonin
- preprohomrone calcitonin is syntehsized by thyroid parafolliculra cells
- it is secreted in response to elevated plasma calcium
- binds to clasts, and causes them to de-attach and therefore decreases bone resorbtion
what is osteogenesis imperfecta
osteopetrosis
Imperfecta
- a defect in collagen genes: mutations leads to brittle bones
Osteopetrosis
- defect in carbonic anhydrase: decreased ability of bone resorbtion: leads to too much bone laydown and not enough breakdown
- results in bone density increased
- increase neurologica disorders because bone compression on nerves
- dimished bone marrow (anemic)
What is Osteoporosis
Osteoporosis
- loss of collagen matrix, loss of calcium phosphate and decreased bone mass
- increased fracutre risk (hips)
- role of bisphosphantes, estrogen and VItD
prevention this via calcium and vit D sup and weight lifting
Vit D Disorders
Excessive
Deficiency
Excessive
- too much intake or over production
- leads to hypercalcemia and toxicity
- leads to elevated plasma phosphate (to counteract)
- treat via: calcitonin or cortisol to block calcium absorbtion from gut
Deficiency
- ricketts: osteomalacia
- inadequate diet, sunlihgt or defect in bodily conversion to proper VIt D
- low calcium and phosphate
- growth failures and deformities
- softening and bending bones
- supplemetn vit D and calcium
Hypoparathyroidism
- autoimmune atrophy of the parathyroid glands or due to surgical removal of the glands
lack ability to make PTH to increase calcium
- hypocalcemia
- elevated phosphate
- hyperactive reflexes, convulsions and excitability of neurons
treatment = clacium and VIt D
Primary Hperparathyroidism
v
Secondary
= a problem with parathyroid galnds themselves: enlargement and overactivity of release of PTH
leads to
- hypercalcemia
- depressed neuromusclar excitability
- massive bone resporbtion (loss)
removal of gland is best treatment
Secondary Hyperparathyroidism
- HIGH PTH due to chornic kidney disease causes high bone turn over
- kidneys dont work: cant convert vit D to its active form
- kidneys odnt work: cant excrete phosphate = increase phosphate
- phosphate binds to calcium: decreaes calcium level in th eserum: triggers PTH to activate
- breaks down bones and increased GI absorbtiion
very common in CKD and gets worse and CKD declines
Symptoms
- osteitis fibrosis cystica: bone pain & subperiosteal bone resorbtion
- brown tumors: from excess clasts breaking down bone and poorly mineralized bone
Treament
- active VIT D & phosphate binders
- calcimimics: to bind to parathyroid and turn off the PTH signal
