Midterm 3 - Lecture 15 Flashcards
What are 5 roles of bones?
- framework and levers allowing conversion of muscle contraction to movement
- protection of internal organs such as brain, lungs and heart
- mineral storage (calcium, phosphate, magnesium and sodium)
- fat storage in marrow (bird marrow cavities contain air sacs)
- production of blood cells
What are 3 types of bones?
- long bones
- flat bones
- irregular bones
Long bones
- elongated cylindrical form
- shaft (diaphysis) and ends (epiphyses)
- supporting columns and levers for muscles
Flat bones
- protect internal organs
- ribs, sternum, pelvic bones and cranium
- attachment for muscles
Irregular bones
- irregular shape, such as vertebrae
What are bones first formed as?
- cartilage; replaced by bone tissue through endochondral ossification
When is the replacement of cartilage by bone tissue (endochondral ossification) complete?
- after puberty
Do bones remain metabolically active after development is complete?
- Yes!
- Calcium and phosphate are mobilized during pregnancy, lactation and other
What is bone mobilization under control of?
- endocrine control
What is the composition and the function of each composition of bone?
40% organic components by weight
- mostly collagen
- withstands tensile forces (bending)
60% inorganic compounds
- mostly calcium phosphate crystals
- withstands compressive forces
When does endochondral ossification start?
- last third of pregnancy from center and the ends
- 3 points of ossification: 2 secondary centers, 1 primary center
Where does growth in bone length occur? What is growth stimulated by?
- at epiphyseal or growth plates
- growth of cells in epiphyseal plate are stimulated by IGF-1
- sex hormones speed up bone growth and mineralization
What happens to bones once an animal is fully mature?
- epiphyseal cartilages become completely ossified
- bone length becomes fixed; growth plates calcify
What 4 cells are involved in bone formation?
- osteoblasts
- osteocytes
- osteoclasts
- osteoprogenitors
Osteoblasts
- synthesize collagen and other organic components to make osteoid
- release calcium salts to form bone (hydroxyapatite)
Osteocytes
- osteoblasts become trapped and become osteocytes
- they maintain bone as living tissue
- long thin cytoplasmic extensions that connect nearby osteocytes by gap jxns
- revert back to osteoblasts as bone matrix dissolved
Osteoprogenitors
- progenitor cells of the bone important in repair and fracture
What are osteoclasts essential for?
- remodeling and removal of mineralized bone
How many nuclei do osteoclasts contain?
- giant cells containing 5-10 nuclei
Where do osteoclasts form?
- on inner and outer bone surfaces by fusion of the monocyte-macrophage cell line
What do osteoclasts do?
- release organic acids to digest bone matrix
- take up minerals by endocytosis and transport them to blood
When and how is bone resorption induced?
when plasma calcium levels drop parathyroid hormone (PTH) induces bone resorption
What is bone remodeling?
regulated degradation and renewal that occurs over longer timescale
- in adults this is a local process where osteoclasts resorb bone, then osteoblasts deposit new bone
- can alter shape and size in accordance with mechanical strain; greater force on bones = greater amount of deposition
What is bone resorption also referred to as?
bone mineralization
Is bone turnover faster in young animals?
- yes!
- complete turnover in 1 year as compared to 20% turned over in adults/yr
- important reason why hypocalcemic conditions such as milk fever is less frequent in young cows
Osteon
- basic functional unit of compact bone; an osteon refers to osteocytes arranged in concentric layers around a central canal
- canals run in parallel to bone surface and contain blood vessels
What do bones of older animals contain a mixture of?
- new and old osteons, and partially resorbed osteons
Where is the majority of body calcium found?
- in bone as hydroxyapatite
What is the composition of plasma calcium?
- 45% free ionized (active)
- 45% bound to proteins
- 10% complexed with anions
What does calcium in extracellular fluid impact?
- signal transduction
What is the concentration of calcium and phosphate regulated by?
- intestinal absorption
- renal excretion/reabsorption
- bone uptake/bone resorption
- all processes hormonally regulated by vit D, PTH, and calcitonin
What is parathyroid hormone produced by?
parathyroid glands
- 1 embedded in the thyroid
- 2nd localized in cranial part of thymus
What happens to PTH if there is low plasma calcium?
increase
What happens to PTH if there is high plasma calcium?
decreases
What role does magnesium play with calcium?
- magnesium plays parallel role to calcium, but with significant Mg depletion there is decrease in PTH leading to hypocalcemia
- magnesium depletion results in tetany
What does PTH promote?
- bone resorption, intestinal absorption and reabsorption in the kidney
- increases synthesis of active form of vitamin D
What does the removal of the parathyroid gland result in?
tetany
What is calcitonin produced by?
C-cells in the thyroid gland
When is calcitonin released?
In response to elevated calcium levels in the plasma
- also stimulated by CCK, gastrin and secretin
What is the fxn of calcitonin?
- reduces calcium concentration in extracellular fluid by inhibiting bone resorption and increasing urinary excretion
- elevated levels reduce population of osteoclasts on bone surface
Is calcitonin essential in terrestrial animals? marine mammals?
Not essential in terrestrial animals, but probably essential for marine mammals due to high calcium concentrations in sea water
Where does vitamin D come from?
consumed in the diet or produced in skin with UV exposure
What type of molecule is Vitamin D?
steroid molecule with open ring structures
What is the most active form of vitamin D?
- Calcitriol (Vit D3)
- Forms of vit D vary in activity
What happens to vitamin D when calcium levels are adequate?
- Vit D is converted to an inactive form and excreted
What happens to vitamin D when calcium levels are low?
- Vit D is converted to calcitriol (the most active form) resulting in increased calcium uptake in the intestine
What is calcitriol considered to be?
Calcitriol is considered to be a hormone as it is produced in one location (kidney) and acts at a different location
How does calcitriol ‘act’?
by binding intracellular receptors in cells that transport Ca2+
Why does supplementation with calcitriol need to be done carefully?
can lead to hypercalcemia
Rickets
- caused by vitamin D deficiency
- young animals continue to produce organic bone matrix (osteoid), but mineralization of matrix doesn’t occur
- results in reduced bone strength and deformation
What can excess vitamin D induce?
- toxicity
- calcium phosphate can precipitate in soft tissue
- high levels in some plants consumed by grazing livestock
How are hindgut fermenters different in terms of the relationship btw Ca2+ and vit D?
- all calcium absorption is independent of Vit D
- Ca2+ pumps in SI are turned on all the time
- since there is no gate controlling Ca2+, removal by the kidney is particularly important
- hypercalcemia is a hallmark of renal failure
What does low blood Ca2+ induce?
- PTH which acts on osteoclasts to mobilize more calcium from bone
- PTH also acts on kidney to reduce urinary excretion of calcium and increase production of calcitriol which increases absorption from the intestine
Why is a cow sometimes unable to mobilize and absorb enough calcium?
- due to the cow having a non-responsive state to PTH
- PTH is not able to go out and act on bone, intestine and kidneys to normalize calcium levels
What is it called if a cow has the inability to normalize calcium levels?
hypocalcemia = milk fever
How is milk fever (hypocalcemia) treated?
- easy to treat if you catch her early by injecting calcium into the milk vein
How can hypocalcemia (milk fever) be prevented?
- feed anionic salts (S or Cl) to induce mild metabolic acidosis
- PTH receptors recognize PTH better at low blood pH
- side effect: feed intake depression
DCAD
Dietary Cation Anion Difference
- different diets vary in proportions of cations and anions, which we are concerned about
- cations: K and Na
- anions: Cl and S
- DCAD = (K+Na) - (Cl+S)
What does a lower DCAD indicate?
- low blood pH and urine pH (mild metabolic acidosis)
- greater capability to maintain Ca homeostatis due to being more responsive to PTH
How low should the DCAD be?
- if negative, we may need a supplement (anionic salts)
- if slightly positive we may be able to use low-DCAD forages
