BSI Lecture 47-48 Bone Physiology Flashcards
What is bone remodeling?
The process of breaking down and replacing bone tissue
What is the purpose of bone remodeling?
- Renew bone before it deteriorates
- Redistributes bone matrix along lines of stress
- Repairs injured bone
- Calcium and phosphate homeostasis
What does BMU stand for?
Bone multicellular unit
What is the BMU composed of?
Osteoblasts and osteoclasts
What do osteoclasts do?
They break down bone and carve small tunnels in the bone
What is the purpose of the ruffled border of osteoclast?
It forms a seal with bone surface
What are the catabolic substances that breaks down bone within Osteoclasts?
Lysosome enzymes and acid
What do the lysosomes inside the osteoclast do?
They digest proteins in the matrix
What does the acid inside the osteoclast do?
Breaks down calcified mineral salts
How is bone resorption or bone turnover measured?
- Collagen breakdown products have pyridinoline structures which can be measured in the urine as an index of rate of bone resorption.
- Serum bone-specific alkaline phosphatase levels are sometimes used in the index of bone turnover.
______ re-build bone.
Osteoblasts
What does osteoblast secrete?
Organic matrix (aka osteoid) and alkaline phosphatase
What are osteoid most made of?
Collagen
What does alkaline phosphatase do?
Initiate calcification of mineral salts
How much of bone mass is being remodeled at any one time?
About 5% by ~2 million BMUs
How do the BMU’s communicate?
By using RANK/RANKL/OPG
Where are RANKL (Receptor Activated of NF-kB ligand) expressed?
In the membrane of osteoblasts and some immune cells
What does RANKL bind to?
RANK on osteoclast precursor cells and osteoclasts to stimulate their activity.
What does binding of RANKL to RANK on osteoclast precursor cells stimulate?
Osteoclastogenesis
What is Osteoclastogenesis?
The formation of new osteolclast
Which BMU produces Osteoprotegerin (OPG)?
Osteoblast and various immune cells
What does OPG do?
Inhibits osteoclastogenesis by binding to RANKL, which prevents them from binding to RANK.
The balance of ______/_______ expression apprears to control the remodeling process.
RANKL/OPG
Name some hormones or cytokines that regulate RANKL/RANK/OPG system?
- PTH (Parathyroid hormone)
- IL-6
- Estrogen
What does PTH do?
Increases RANKL expression and suppresses OPG expression in osteoblasts and some immune cells. (increases bone resorption)
What does IL-6 do?
Increases RANKL expression and suppresses OPG. (increases bone resorption)
What does estrogen do?
Stimulates OPG expression and suppresses RANKL expression. (Decreases bone resorption)
What is bone resorption?
The process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.
Bone is a major reservoir for ____ and _____.
Calcium; phosphate
99% of ______ is stored in the skeleton.
Calcium
Where is the 1% of calcium that is not in the skeleton?
In the plasma
What are glucocorticoids and what do they do?
They are steroid hormones that increases resorption. (Used in organ transplants that suppress immune system)
What is the biologically active form of Calcium?
Ionized-not bound to anything
What are the inactive forms of Calcium?
Bound form (to albumin (41%) and anions(9%)
Why is calcium important?
Important in
- Blood clotting
- Muscle contractions
- Nerve Function
What are the signs and symptoms of hypocalcemia?
- Spontaneous action potentials due to increased Na permeability
- Paresthesias (tingling)
- Tetany (first see in hands, wrists; occur in laryngeal muscles which can kill you)
- Cardiac arrythmias
- Seizures.
What are the signs and symptoms of more severe hypercalcemia?
- Nervous system depression
- Sluggish reflexes
- Muscle weakness
- Lethargy and fatigue
- Constipation
- Decreased appetite
- Nausea and vomiting
- Frequent urination (polyuria)
- Excessive thirst (polydipsia)
What is polyuria?
Production of abnormally large volume of dilute urine. Kidneys become insensitive to ADH (Anti-Diuretic Hormone(from pituitary gland)) which causes excess urination.
__________ is a monoclonal antibody that binds to the RANKL (acts similary to OPG)
Denosumab
What does ADH (Anti-Diuretic Hormones (from pituitary gland)) do?
It causes the kidneys to reabsorb water to be put back into the blood.
What are the signs and symptoms of most severe hypercalcemia?
a. Nervous system depression
b. Sluggish reflexes
c. Muscle weakness
d. Lethargy and fatigue
e. Constipation
f. Decreased appetite
g. Nausea and vomiting
h. Frequent urination (polyuria)
i. Excessive thirst (polydipsia)
j. Kidney stones
What are the symptoms of hypophosphatemia?
a. Muscle dysfunction and weakness
b. Mental status change, from irritability to gross confusion, delirium and coma.
c. Instability of cell membranes due to low ATP levels; this may cause rhabdomyolysis and hemolytic anemia.
What is a major sign of hyperphosphatemia?
Calcium levels will be lowered due to precipitation of phosphate with the calcium in tissues.
What is ectopic calcification?
A pathological deposition of calcium salts in tissues or bone growth in soft tissues.
85-90% of _______ is stored in the skeleton?
Phosphate
2/3 of plasma phosphate is in _______ compounds.
Organic
1/3 of plasma phosphate as _______ phosphate.
Inorganic (Pi)
PTH _______ plasma calcium and ______ plasma phosphate.
Increases; decreases
What stimulates PTH release from the parathyroid gland?
Low plasma calcium levels
What can act directly on the parathyroid glands and decrease PTH secretion?
1,25 hydroxyvitamin D3 (1,25(OH)2D3 )
PTH _________ bone resorption.
Increases
T or F? PTH decreases intestinal absorption of calcium and phosphate via activation of vitamin D.
False, increases
PTH increases activity of 1-alpha-OHase in the ________
Kidneys
PTH increases the reabsorption of _____ by the kidneys
Calcium
How does PTH decrease blood phosphate levels?
By decreasing reabsorption by the kidneys
Calcitonin __________ plasma calcium and phosphate.
Decreases
Where is calcitonin secreted from?
Parafollicular cells of thyroid gland
What causes stimulation of calcitonin release?
High plasma calcium levels
Does calcitonin increase or decrease bone resorption?
Decrease
T or F? Calcitonin decreases reabsorption of calcium and phosphate by the kidneys?
True, the body gets rid of it in the urine
Vitamin D _________ plasma calcium and phosphate.
Increases
What effect does Vitamin D have on intestinal absorption of calcium and phosphate?
It increases intestinal absorption
What minor effect does vitamin D have on kidneys?
Increases reabsorption of calcium and phosphate
How is vitamin D metabolized?
It is converted in the liver by Vitamin D-25-hydroxylase to 25-hydroxyvitamin D3 [25(OH)D3]
Where does vitamin D2 and D3 come from?
From the coversion of 7-dehydrocholesterol in the skin by solar ultraviolet B radiation of from dietary sources.
What is the major circulating form of vitamin D in the blood that is measured to assess vitamin D status of an individual?
[25(OH)D3]
25(OH)D3 is an inactive form of Vitamin D that must be converted in the ____________.
Kidneys
How is 1,25 hydroxyvitamin D3 formed?
It is formed by the the enzyme 25-hydroxyvitaminD-1-alphahydroxylase(1-alpha-OHase)
What is another name for 1,25 hydroxyvitamin D3?
Calcitriol
T or F? PTH stimulates activity of 1-alpha-OHase in the liver and therefore is integral in the activation of vitamin D
False, kidney
The renal production of 1,25(OH)2D3 is used for regulating ________ and _________ metabolism.
Calcium; phosphorous
T or F? There appears to be a hierarchy in utilization of vitamin D in the body.
True
What are the hierarchy levels of calcium?
- Vitamin D maintains plasma calcium levels primary by increasing intestinal calcium absorption.
- Only when extracellular ionized calcium requirement is met will 25(OH)D3 be used by other tissues and be converted locally to 1,25(OH)2D3
What does Vitamin D reduce?
a. Risk of variety of cancers
b. Hypertension
c. Heart disease
d. Infectious disease
e. mmultiple sclerosis
f. rheumatoid arthritis
g. asthma
h. depression
i, type 1 diabetes
j. metabolic syndrome
How has vitamin D been linked to the aging process?
Higher vitamin D levels associated with longer telomeres.
T or F? HIgher vitamin D levels has been associated with greater weight loss in dieting individuals.
True
T or F? More the 50% of population gets insufficient vitamin D.
True