Flashcards in Exam #4: Calcium and Bone Physiology Deck (40):
List the plasma forms of calcium.
There are three forms of Ca++ in the plasma:
1) Free/ ionized Ca++ (50%)
2) Calcium that is bound to protein i.e. albumin (40%)
3) Ca++ bound to small diffusible anions (10%)
In which form is ~ 50% of the total calcium?
Free/ ionized Ca++
*Note that this is the only form of Ca++ that is biologically active & regulated
Which forms of Ca++ are filtered in the glomerulus?
Ca++ that is NOT protein bound i.e. 60% of the total Ca++ in plasma is filtered at the glomerulus
How does pH effect Ca++ in the plasma?
Alkaline pH= more Ca++ bound to protein
Acidic pH= less Ca++ bound to protein
What are the symptoms of hypocalcemia?
Hypocalcemia causes threshold to become CLOSER to membrane potential (more negative), which makes nerves & muscles MORE excitable. Symptoms include:
1) Hypocalcemic tetany
2) Latent tetany revealed by Trousseau or Chvostek sign
6) Syncope, CHF, and angina
*Chovstek sign= tapping on the facial nerve that elicits twitching of the facial muscles
Trousseau sign= carpopedal spasm upon inflation of a blood pressure cuff
What are the symptoms of hypercalcemia?
Hypercalcemia causes threshold to more FARTHER from resting membrane potential (more positive), making nerves and muscles LESS excitable. Symptoms include:
2) Muscle weakness
5) Kidney stones
7) Cardiac arrest
Describe the regulation of plasma Ca++.
- Ca++ homeostasis involves the coordinated interaction of the: bone, kidneys, and GI tract
- Balance is attained when renal excretion= GI absorption of Ca++
On a daily basis:
- 1,000mg Ca++ ingested but only 350mg absorbed in the GI tract
- 150 mg secreted into the salivary, pancreatic, and intestinal fluids
- Net 200mg is absorbed, which much be excreted by the kidneys to be in balance
*Note that 1,25-dihydroxycholecaliferol (active Vitamin D) increases GI absorption of Ca++
What hormone increased GI absorption of Ca++?
Active form of Vitamin D
Describe the regulation of plasma phosphorus.
GI Tract: most of the dietary phosphorus is absorbed
- Vitamin D controls uptake
Bone: phosphorus is part of the major bone crystalline salt, hydroxapatite
Kidney: at low levels all phosphate is reabsorbed but at higher & higher levels some is excreted
- PTH increases phosphate excretion
- Fibroblast growth factor 23 (FGF 23) is a peptide hormone synthesized by osteoblasts and osteocytes that increases renal excretion of phosphate
Why does hydroxyapatite precipitate in bone and not in other tissues?
Inhibitors found in other body tissues including plasma prevent precipitation
Outline the mechanism of bone growth and calcification.
1) Osteoblasts secrete collagen and ground substance
2) Osteoblasts become trapped in osteoid and become osteocytes
3) Ca++ salts precipitate onto collagen and then hydroxyapatite crystals form
What cells are responsible for bone deposition?
Which cell type is responsible for bone resorption?
Describe bone remodeling.
Bone remodeling, or the deposition of new bone and reabsorption of old bone, is a continuous process
What is the general function of PTH in bone remodeling?
Stimulation of osteoclasts and bone resorption
How does PTH stimulate bone resorption?
PTH stimulates bone resorption indirectly:
1) Binds osteoBLASTS and causes them to release cytokines 2) Cytokines, osteoprotegerin ligand (OPLG) activate receptors on preosteoCLAST cells
3) PreosteoCLAST cells differentiate into osteoCLASTS that promote bone resorption
What are the roles and alternate names of: OPGL and OPG? Which increases bone resorption?
OPLG= "Osteoprotegerin Ligand" is a cytokine released from osteoBLASTS that induces the differentiation of osteoCLASTS in response to PTH binding to PTH receptors on osteoBLASTS
- OPLG thus increases bone resorption
- OPLG is also called "RANK Ligand"
OPG= "Osteoprotegerin," is a cytokine produced by osteoBLASTS that INHIBITS bone resorption by acting as a decoy receptor for OPGL
What is the name for this most active form of vitamin D?
Where is vitamin D3 converted (2 steps, 2 organs) into the most active form of vitamin D?
Kidney= PTH converts 25-hydroxycholcalciferol into 1,25-dihydroxycholecalciferol
- Enzyme= 1-alpha hydroxylase & is essential for the formation of ACTIVE Vitamin D
What hormone is required for the kidneys to convert Vitamin D into its active form?
What is the function of Vitamin D in the GI tract?
Stimulation of Ca++ & phosphate absorption
What is the function of Vitamin D in the Kidney?
Stimulation of Ca++ & phosphate reabsorption
What is the function of Vitamin D on the bones?
Promotes PTH activity on osteoclasts i.e. promotes PTH mediated bone resorption
What is the dose-dependent effect of Vitamin D on the bones?
Small amounts of Vitamin D promote calcification
What is osteomalacia?
Softening of new bone in adulthood due to deficient mineralization-->bending in weight-bearing bones
- Caused by a failure of a damaged kidney to produce the active form of Vitamin D
Describe how/why renal disease can cause osteomalacia.
- Kidney is required for the formation of the active form of Vitamin D
- Vitamin D promotes bone calcification
- Without Vitamin D, bones are soft due to deficient calcification/ mineralization
What is the primary stimulus for PTH secretion?
Low ECF Ca++
What is the general function of PTH?
PTH generally functions to regulate the concentration of Ca++ in the ECF; it increases Ca++ in the ECF BUT DECREASE phosphate
*****Note that a lack of PTH will lead to death from hypocalcemia tetany
Why is the action of PTH to decrease phosphate important?
Increase in Ca++ & decrease in phosphate prevents crystallization of calcium phosphate
What are the actions of PTH on the kidney?
1) PTH increases the amount of Ca++ reabsorbed in the distal portions of the nephron
2) PTH inhibits phosphate reabsorption from the kidney
3) PTH increases 1a hydroxylase, the enzyme in the kidney that forms active Vitamin D
What is the action of PTH in regards to Vitamin D?
1) Increases the enzyme that forms active Vitamin D in the kidney
2) By the action of Vitamin D (indirect), increases uptake of Ca++ & phosphorus from the GI
What is the function of Calcitonin (CT)?
Decrease bone resorption & Ca++ release
What is the stimulus for CT release?
Elevated plasma Ca++
What are the causes and symptoms of primary hyperparathyroidism?
Primary hyperparathyroidism is caused by enlargement of one or more of the parathryoid glands, leading to hypercalcemia and hypophosphatemia. Symptoms include:
- Ca++ kidney stones
- Weak bones & bone fractures from bone resorption
- Constipation & excessive urination
What are the causes and symptoms of secondary hyperparathyroidism?
- Secondary hyperparathyroidism occurs in patients with diseases that cause chronically low plasma Ca++
- Low ECF Ca++ leads to COMPENSATORY hyperstimulation of the parathyroid gland, hypertrophy, & HYPERPARATHYROIDISM
- Symptoms are the same as for primary hyperparathyroidism
What are the causes and symptoms of hypoparathyroidism?
Hypoparathyroidism is caused by parathyroidectomy i.e. accidental damage during thyroid surgery, and can lead to a steady decline in plasma Ca++. Symptoms include:
- Neuromuscular excitability
- Hypocalcemia tetany
What are the causes and symptoms of pseudohypoparathyroidism?
Pseudohypoparathryoidism occurs when patients have signs and symptoms of hypoparathyroidism, but PTH levels are normal or elevated. This is caused by a defect in the PTH receptor, or in the tissue response to PTH. Symptoms include symptoms of hypocalcemia.
What is the difference in the effects of PTH and FGF23 on PTH and Calcitriol?
BOTH increase phosphate excretion by the kidneys
Opposite effects on calcitriol
- PTH= increases renal production of calcitriol
- FGF23= decreases renal production of calcitriol
What is the role of estrogen in bone remodeling?
Estrogen stimulates OPG production, which is a cytokine that acts as a decoy for OPGL
****Thus, estrogen PREVENTS bone resorption, which is why post-menopausal women are at increased risk for osteoporosis