Unit 3: Human Phys Ca2+ Homeostasis

What do hormones directly or indirectly play important roles in?

controlling growth

What are the 5 hormonal influences on growth?

1. Growth hormone and “insulin-like” growth factors

2. Thyroid hormones

3. Insulin

4. Sex hormones (testosterone, estrogen)

5. Cortisol

Insufficient amounts of _____ _____, _____ _____, ________, or ________ interfere with growth

amino acids, fatty acids, vitamins, minerals

At least how many or more hormones, vitamins, and growth factors affect osseous tissue?

20

When is bone growth especially rapid?

puberty and adolescence

During bone growth, specifically during puberty and adolescence, what happens that promotes ossification?

surges of growth hormone, estrogen, and testosterone occur

What does the surging of growth hormone, estrogen, and testosterone cause, especially during bone growth specifically during puberty and adolescence?

these hormones stimulate multiplication of osteogenic chondrocyte multiplication, matrix deposition by osteoblasts, chondrocyte multiplication, and hypertrophy in metaphyses

Define epiphyseal plate (growth plate)

area of hyaline cartilage that separates epiphyses and diaphyses of children’s bones

What does the epiphyseal plate (growth plate) allow?

enables growth in length

Define epiphyseal line

in adults, a bony scar that marks where growth plate used to be

What are the 6 features of bones?

1. Long bone

2. Epiphyses and diaphysis

3. Compact and spongy bone

4. Marrow cavity

5. Articular cartilage

6. Periosteum

Define bone

connective tissue that consists of cells, fibers, and ground substance

What are the four principal types of bone cells?

1. Osteogenic cells

2. Osteoblasts

3. Osteocytes

4. Osteoclasts

Define osteogenic cells

stem cells found in endosteum and inner layer of periosteum

What are 2 features of osteogenic cells?

1. Arise from embryonic mesenchymal cells

2. Multiply continuously and give rise to other bone cell types

Define osteoblasts

bone-forming cells

What are the 5 features of osteoblasts?

1. Form single layer of cells under endosteum and periosteum

2. Nonmitotic

3. Synthesize soft organic matter of matrix which then hardens by mineral deposition

4. Stress stimulates osteogenic cells to multiply rapidly and increase the number of osteoblasts which reinforce bone

5. Secret hormone osteocalcin

What are 2 features of osteocalcin?

1. Stimulates insulin secretion of pancreas

2. Increases insulin sensitivity in adipocytes which limits the growth of adipose tissue

Define osteocytes

former osteoblasts that have become trapped in the matrix they deposited

Define lacunae

tiny cavities where osteocytes reside

Define canaliculi

little channels that connect lacunae

What are the 4 steps that happen with osteocytes in bone cells?

1. Cytoplasmic processes of osteocytes reach into canaliculi and contact processes of neighboring cells

2. Gap junctions allow for passage of nutrients, wastes, signals

3. Some osteocytes reabsorb bone matrix while others deposit it

4. Act as strain sensors- when stressed, produce biochemical signals that regulate bone remodeling (shape and density changes that are adaptive)

Define osteoclasts

bone-dissolving cells found on bone surface

What are 6 features of osteoclasts?

1. Osteoclasts develop from same bone marrow stem cells that give rise to blood cells (different origin from other bone cells)

2. Very large cells formed from fusion of several stem cells

3. Have multiple nuclei in each cell

4. Ruffled border (large surface area) faces bone

5. Cells often resides in resorption bays (pits in bone surface)

6. Dissolving bone is part of bone remodeling

What does the histology of compact bone reveal?

osteons (haversian systems)

In regards to compact bone, what does the concentric lamellae do?

concentric lamellae surround a central (haversian) canal

In regards to compact bone, what are perforating (Volkmann) canal?

transverse or diagonal passages

In regards to compact bone, what does circumferential lamellae do?

fill outer region of dense bone

In regards to compact bone, what does interstitial lamellae do?

fill irregular regions between osteons

What is the matrix of osseous tissue, by dry weight, about what?

one-third organic and two-thirds inorganic matter

Define organic matter

synthesized by osteoblasts

What makes up organic matter?

collagen, carbohydrate- protein complexes, such as glycosaminoglycans, proteoglycans, and glycoproteins

What is inorganic matter?

85% hydroxyapatite (crystallized calcium phosphate salt), 10% calcium carbonate, other minerals (fluoride, sodium, potassium, magnesium)

What does it mean when it is said that bone is composite material?

bone is a combination of a ceramic and a polymer

What are the 3 features of bone being a composite material?

1. Hydroxyapatite and other minerals are the ceramic and collagen (protein) is the polymer

2. Ceramic portion allows the bone to support body weight without sagging

3. Polymer (protein) gives some flexibility

What is Rickets disease?

caused by mineral deficiency and resulting in soft, deformed bones

What is Osteogenesis imperfecta (brittle bone disease)?

results from a defect in collagen deposition

What (absorption and deposition) occurs throughout the life- 10% of skeleton per year?

bone remodeling

What does bone remodeling do?

repairs microfractures, releases mineral into blood, reshapes bones in response to use or disuse

Define Wolff’s law of bone

architecture of bone determined by mechanical stresses placed on it

Along with Wolff’s law of bone, what goes along with this process?

remodeling is a collaborative and precise action of osteoblasts and osteoclasts and bony processes grow larger in response to mechanical stress

A mature bone remains a what?

metabolically active organ

What are the features of a mature bone?

involved in its own maintenance of growth and remodeling and exerts a profound influence over the rest of the body by exchanging minerals with tissue fluid

What does the disturbance of calcium homeostasis in skeleton cause?

disrupts function of other organ systems, especially nervous and muscular

Define mineral deposition (mineralization)

process in which calcium, phosphate, and other ions are taken from the blood and deposited in bone

Describe the 4 steps of mineral deposition (mineralization)

1. Osteoblasts produce collagen fibers that spiral the length of the osteon

2. Fibers become encrusted with minerals

3. Hydroxyapatite crystals for at solubility product

4. First few crystals act as seed crystals that attract more calcium and phosphate from solution

Define solubility product in regards to mineralization

critical level of calcium times phosphate concentration

Define mineral resorption

process of dissolving bone and releasing minerals into blood

What are the 5 steps of mineral resorption?

1. performed by osteoblasts at ruffled border

2. hydrogen pumps in membranes secrete hydrogen into space between osteoclast and bone surface

3. chloride ions follow by electrical attraction

4. hydrochloric acid (pH 4) dissolves bones minerals

5. acid phosphatase enzyme digests collagen

6. Release of minerals into bloodstream

What are the 4 aspects (from the powerpoint) which describe calcium homeostasis?

1. calcium and phosphate are used for much more than bone structure

2. Phosphate is a component of DNA, RNA, ATP, phospholipids, and pH buffers

3. Calcium needed in neuron communication, muscle contraction, blood clotting, and exocytosis

4. minerals are deposited in the skeleton and withdrawn when they are needed for other purposes

Calcium storage, absorption into the body and excretion from the body occur at 3 main sites:

bone, kidneys, gastrointestinal tract

How much calcium is in the adult body?

total of about 1100 g of calcium in adult body with 99% of it in the bones

What are 2 things that can be said about the calcium in the adult body?

most exists as part of hydroxyapatite, but a little is in a form that is easily exchanged with the blood and about 18% of skeletal calcium is exchanged with blood each year

What is the normal calcium concentration in blood plasma?

9.2 to 10.4 mg/dL

What are 2 things that can be said about the normal calcium concentration in blood plasma being 9.2 to 10.4 mg/dL?

45% as Ca+ that can filter between cells of capillary walls and affect other tissues and rest in reserve, bound to plasma membrane

Define hypocalcemia

deficient calcium in blood

What are 3 1/2 aspects of hypocalcemia?

1. changes membrane potentials and causes overly excitable nervous system and tetany (muscle spasms)

1a. Laryngospasm can cause suffocation

2. caused by vitamin D deficiency, diarrhea, thyroid tumors, underactive parathyroid glands

3. pregnancy and lactation increase risk of hypocalcemia

Define laryngospasm

involuntary contraction of the vocal cords, leading to difficulty breathing

Define hypercalcemia

excessive calcium levels

What are 3 aspects of hypercalcemia?

1. makes ion channels less responsive and thus nerve and muscle are less excitable

2. can cause emotional disturbance, muscle weakness, sluggish reflexes, cardiac arrest

3. hypercalcemia rarely occurs

What does calcium homeostasis depend on?

the balance between dietary intake, urinary and fecal losses, and exchanges between osseous tissue

What 3 hormones is calcium homeostasis regulated by?

calcitriol, calcitonin. and parathyroid hormone

Describe how the 3 hormones: calcitriol, calcitonin, and parathyroid hormone. work together in regards to calcium homeostasis

These hormones work together to maintain calcium levels in the blood, where calcitriol increases absorption in the intestines, calcitonin reduces calcium levels by inhibiting bone resorption, and parathyroid hormone raises calcium levels by stimulating bone resorption and renal reabsorption.

What are the 2 hormones that regulate plasma calcium concentration?

parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol)

Does calcitonin play a major or limited role in calcium homeostasis?

limited

What is the most active form of vitamin D?

calcitriol

How is calcitriol produced?

by actions of skin, liver, and kidneys

Describe the 3 ways calcitriol is produced

1. epidermal keratinocytes use UV radiation to convert 7-dehydrocholestrol to previtamin D3; sun on skin

2. liver adds hydroxyl group converting that to calcitriol

3. kidney adds hydroxyl group converting that to calcitriol

Calcitriol is a hormone that does what?

raises blood calcium level

Specifically, what 4 aspects are associated with calcitriol raising blood calcium level?

1. it mainly increases calcium absorption by small intestine

2. it also increases calcium resorption from the skeleton

3. stimulates osteoblasts to release RANKL, a chemical that stimulates production of more osteoclasts

4. it weakly promotes kidney reabsorption of calcium ions, so less lost in urine

When calcitriol binds to Vit D receptors, what does it then function as?

functions as a transcription factor to upregulate genes coding for Ca2+ binding proteins

Define TRPV6

a cation channel highly selective to Ca2+

Define calbindin

a Ca2+ binding protein

Calcitriol is necessary for what?

bone deposition- helping provide adequate calcium and phosphate

Inadequate calcitriol results in what in children and what in adults?

results in abnormal softness in children (rickets) and in adults (osteomalacia)

Define calcitonin

secreted by C cells (clear cells or parafollicular cells) of thyroid gland when blood calcium levels rise too high

What 2 ways does calcitonin lowers blood calcium concentration?

inhibits osteoclasts thereby reducing bone resorption and stimulates osteoblasts to deposit calcium into bone

Why does calcitonin have more of an effect in children than in adults?

osteoclasts more active in children due to faster remodeling

Calcitonin may inhibit what in pregnant and lactating women?

bone loss

How does calcitonin directly inhibits activity of osteoblasts?

inhibits motility and cell shape, thus inactivating them

List the 6 hormones that favor bone formation and increased bone mass

1. insulin

2. growth hormone

3. insulin-like growth factor 1 (IGF-1)

4. estrogen

5. testosterone

6. calcitonin

List the 3 hormones that favor increased bone resorption and decreased bone mass

1. parathyroid hormone (chronic increases)

2. cortisol

3. thyroid hormone T3

Define parathyroid hormone (PTH)

secreted by parathyroid glands on posterior surface of thyroid

When is PTH released?

when calcium levels are low in the blood

PTH raises calcium blood level by four mechanisms, what are they?

1. stimulates osteoblasts to secrete RANKL, thereby increasing osteoclast population and bone resorption

2. promotes calcium reabsorption by kidneys, so less lost in urine

3. promotes the final step of calcitriol synthesis in the kidneys, enhancing calcium-raising effects of calcitriol

4. inhibits collagen synthesis by osteoblasts, inhibiting bone deposition

PTH indirectly stimulates what?

stimulates osteoclast production/activity

What three things maintain normal blood calcium concentration?

calcitriol, calcitonin, and PTH

What is the average amount of phosphorus doe adults have?

500 to 800 g of phosphorous with 85% to 90% of it in the bones

For phosphate homeostasis, what is the normal plasma concentration?

3.5 to 4.0 mg/dL

Phosphate homeostasis occurs in 2 forms, what are they?

HPO4²- and H2PO4^- (monohydrogen and dihydrogen phosphate ions)

Are phosphate levels more or less regulated than calcium levels?

phosphate levels not regulated as tightly as calcium levels

What does calcitriol do in regards to phosphate levels?

raises phosphate levels by promoting its absorption by small intestine

What does PTH do in regards to phosphate levels?

lowers blood phosphate levels by promoting its urinary excretion

Does estrogen or testosterone have a stronger effect on bone growth?

estrogen

What causes growth to stop?

anabolic steroids

What happens when anabolic steroids are administered to the body?

epiphyseal plate “closes” prematurely and results in abnormally short adult stature

Describe rickets and osteomalacia and why are these conditions caused?

Rickets (in children) and osteomalacia (in adults) are conditions in which mineralization of bone matrix is deficient, causing the bones to be soft and easily fractured. A major cause of rickets and osteomalacia is deficiency of vitamin D

What is osteoporosis and what does it result in?

an imbalance between bone resorption and bone formation resulting in decreases in bone mass and strength leads to an increased incidence of fractures

What type of people does osteoporosis occur in?

can occur in people who are immobilized, in people who have an excessive plasma concentration of a hormone that favors bone resorption, and in people who have a deficient plasma concentration of a hormone that favors bone formation

Osteoporosis is most commonly seen with what?

aging