Calcium, phosphate and bone homeostasis
From Iusmphysiology
- started here on 02/28/11 at 11AM
[edit] Calcium, phosphate, and bond homeostasis
[edit] Objectives
- He will take exam questions from these!
[edit] Overview of Ca
- Almost all Ca of body is locked up in the bone.
- Ca is required for many physiological things like:
- Maintaining Na permeability
- Triggering release of NTs
- Excitation-contraction coupling
- An intracellular signalling molecules
- Co factors for many enzymes
- Required for exocytosis
- Must know the fxns!
[edit] Overview of Phosphate
Missed this slide
- Much phosphate in intracellular fluid and not much in extracellular fluid.
[edit] Bone inorganics
[edit] Distribution of plasma calcium
- About half of one's plasma calcium is filterable.
- Easiest to regulate is that which is filterable
- Also called ionized
- The rest of the calcium is unfilterable
- Some is complexed to other molecules
- About 40% is bound to proteins
- These are regulated only in emergency situations
- Ca levels are very tightly regulated.
[edit] Phosphorous in plasma
- Vary dramatically
- 3.0 mg/dL - 4.5 mg/dL
- As blood becomes more acidic (pH goes down), more phosphate will be converted to dihydrogen phosphate (H2PO4-).
- Unlike calcium, all inorganic phosphate is filterable.
[edit] Where do we get ca?
- Most is in our bones and ofr the most part we try to keep it that way
- We only reabsorb it when the body needs it.
- Usually we get Ca through intestinal absorption of Ca from diet.
- Ca can move pericellularly but this is restricted by tight junctions so it is not just random diffusion.
- But most of the Ca we absorb is through active transport into the epithelial cell on the apical layer, then get bound by regulatory proteins that buffer the Ca levels witn the epithl cell, and then dumped out of the cell via Ca transporters (often H-Ca or Na-Ca exchangers).
- 1,25 dihydroxy vitamin D is important b/c it acts as a txn factor to regulate genes that help transport Ca from lumen to blood.
- Includes calbindin.
[edit] Where do we get phosphate?
- Hyrdrogen phosphate and dihydrogen phosphate are the two major forms absorbed.
- Into epith via Na-Phos cotransporter
- Uses Na gradient
- Outof epith via Na-K exchanger and some relatively unknown transporters.
[edit] Calcium homeostasis and bone turnover
[edit] Mechanisms of action of caclcitropic hormones
- PTH
- VitD
- Calcitonin
[edit] PTH
- Comes from parathyroid
- Well studied, well understood.
- Eli Lilly developed synthetic PTH
- Used to treat bone and other disease
- Made in parathyroid gland
- Made as preprotein
- Has a singal sequence for moving protein over membrane and out of the cell
- Cleaved off to become prosequence
- Fxn?
- Then prosequence gets cleaved off to form ?
- This is the drug form is PTH 1-33 or 1-34.
- PTH increased in response to low serum Ca levels.
- PTH then acts on various targets to return Ca to normal range.
[edit] Calcitonin
- As Ca gets too high calcitonin is secreted
- CT = calcitonin
- Removes calcium from the blood
- Increases bone formation by reincorporating Ca into bone
- INcreased Ca loss at urine
- Decreased Ca absorption at the gut
[edit] VitD
- Bio active form is 1,25 dihyroxy VitD
- We can injest vitD
- We can create vitD at our skin from 7-dehydroxycholeterol (de novo)
- 7-dehydroxycholesterol -> cholecalciferol -> 25 OH D2 at liver -> 1,25 OH D3 at kidney (PTH can increase this)
- PTH increases by increasing 1alpha l-hydroxylase which acts at the kidney to add the second OH group
- So decreasing phophate in serum stimulates PTH and stimulates 1alpha-hydroxylase activity at the kidney.
[edit] Roles of hormones at targets
- MOst important slide!
[edit] Pathway
- See chart if this is confusing.
- Note that calcium regulation is more important than phosphate.
[edit] Osteoporosis
Got distracted at about 11:34AM.
[edit] Osteoporosis definition: NIH concensus conference
- Strength = density + quality
- Quality is a fxn of
- architecture
- Damage accumulation
- turnover
- etc.
[edit] Symptoms
- Called the silent disease
- Bone loss usually occurs without disease
- First symptom is usually a non-traumatic bone fracture
- Like when old people fall, it is often because the hip breaks (first) and thus causes the fall (second).
- Look for osteoporosis in the vertebrae
- Can lead to severe back pain.
[edit] Epidemiology
- Not going to be tested
[edit] Risk factors
- Personal histroy of fracture after 50
- Low bone mass, even without fracture
- Genetics, family history
- Being female
- Being thin or having small frame
- Advanced age
- Estrogen deficiency following menopause
- Especially surgically induced or early onset
- Women can lose up to 20 percent of their bone mass in 5 to 7 years following menopause
- Abnormal menstrual cycle
- Long distance runners
- Anorexia
- Low lifetime calcium intake
- VitD deficiency
- Low testosterone levels in men
- Inactivity
- Excessive use of alcohol
- Caucasians or asian
[edit] Diagnosis
- BMD test
- Gives T score: pt's score - young adult's average score then divided by 1 SD of mean of young adult BMD
- Gives Z score: pt's score - mean aged matched BMD / 1 SD of aged matched BMD
- If T score = -1 to +1
- Means you are within on SD
- If T score = -2.5 to -1
- Means you have low bone mass
- < 2.5
- Osteoporotic
[edit] Other bone disorders
- NOT ON THE EXAM!
- Osteomalacia
- Poor nutrition
- Poor mineralization
- Rickets is childhood form
- Prevalent in 20s and 30s
- Making a bit of a come-back.
- Supplement with vitD
- Paget's disease:
- stopped here on 02/28/11 at 12PM.
