Module 1 Section 6 (Growth and Calcium Metabolism)

Question 1

Describe how growth hormone is secreted and outline its anabolic effects on bone and tissue.

Answer 1

.

Question 2

Explain the process for elongating the long bones and how it is hormonally regulated.

Answer 2

1) In this region, there are cartilage forming cells called chondrocytes. When they divide, they stack themselves in columns with newer cells towards the epiphysis and older cells near the diaphysis.
2) This division and increase in the # of chondrocytes = long bones elongation. As chondrocytes mature, they hypertrophy (which further pushes the epiphysis away from the diaphysis and the matrix around them calcifies).
3) However, cartilage itself is not highly vascularized and eventually the older chondrocytes are too far away from the nearest nutrient supply and they die.

4) Osteoclasts will now remove the dead chondrocytes and the calcified matrix, allowing
osteoblasts (and their capillary supply) to invade this new space and start depositing bone through the process of ossification.

5) The formation of new chondrocytes is matched to the removal of dead chondrocytes such that the width of the epiphyseal plate remains fairly constant as the bone lengthens.

At the end of adolescence, sex hormones cause the epiphyseal plates to completely ossify and linear bone growth ceases. Thickening of bone can occur throughout life, though.

Question 3

Describe the hormonal regulation of plasma calcium. **

Answer 3

Ca is under hormonal control to ensure the proper conc is maintained.

It can be ingested through your diet to enter the plasma and excess Ca is generally stored in the bones.

• During periods of high dietary intake of Ca, excess Ca is avoided by decr absorption.
• When there is a need for incr Ca in the plasma, Ca can readily be removed from the bones.

There are 3 hormones that regulate the plasma concentrations of Ca. They are:

1) Parathyroid hormone (PTH)
2) Calcitonin
3) Vitamin D

Question 4

What are the 2 main periods of rapid growth?

Answer 4

1) The first 2 yrs of life

2) Puberty

Question 5

Discuss the differences in hormones secreted during puberty growth for males and females.

Answer 5

In both males and females, pubertal growth is supported by growth hormone and androgens.
- DHEA is the primary androgen responsible for stimulating growth in females. Meanwhile, in males it’s testosterone

Question 6

What actions does GH have?

Answer 6

Metabolic actions
1. Incr rate of protein synthesis
2. Incr FA mobilization and use
3. Decr rate of glucose use by body tissues
- Shifts body to primarily use fat stores for metabolism while sparing
glucose (can be important during prolonged fasting as it preserves glucose for the brain).

Soft tissue actions
- For soft tissues that’re sensitive to GH stimulation, GH can incr the # of cells (hyperplasia) by stimulating cell division or cells to grow larger (hypertrophy) by promoting protein synthesis.

Question 7

True or false: bone is inert (lacking the ability or strength to move).

Answer 7

False

It’s actually a very active and dynamic tissue

Question 8

Bones are highly vascularized and dynamic. They are almost constantly being remodeled due to the activity of two cell types. What are they?

Answer 8

1) Osteoblasts that deposit new bone

2) Osteoclasts that dissolve bone.

Question 9

What are the 2 types of bone growth?

Answer 9

1) Bone Growth in Thickness
- It occurs by adding new bone to the outer layer of existing bone.
- As osteoblasts are depositing new bone on the outer surface of a bone, osteoclasts on the inside of the bone are removing bone.
- Thus, both the diameter of bone and the marrow cavity will increase.

2) Bone Growth in Length
- It’s the lengthening of long bones only occurs at its ends b/w the epiphysis (the knob at the end) and the diaphysis (the shaft of the bone) in the epiphyseal plate.

Question 10

Define marrow cavity

Answer 10

The central cavity of bone shafts where red bone marrow and / or yellow bone marrow
(adipose tissue) is stored. It is also called the medullary cavity.

Question 11

True or false: during puberty, there’s a large acceleration in the lengthening of long bones.

Answer 11

True

Especially in males

Question 12

The effects of GH are actually mediated through peptides known as somatomedin, also called insulin-like growth factors (IGFs). There are two IGFs. What are they?

Answer 12

IGF-I

• GH stimulates the synthesis and release of IGF-I (primarily in the liver).
• Most other tissues can also produce IGF-I when stimulated by GH but don’t release it into the
  blood. However, this IGF-I may have paracrine actions.
• It mediates most of the growth promoting actions of GH.

IGF- I I

• GH doesn’t stimulate the production of IGF-II.
• IGF-II is important during fetal development.
• It’s produced in adults but its role is not clear

Question 13

Growth hormone has two regulatory hormones from the hypothalamus. What are they?

Answer 13

1) Growth hormone-releasing hormone (GHRH) stimulates its release.
2) Growth hormone-inhibiting hormone (GHIH; aka somatostatin) inhibits its release.

Having these 2 modulatory factors incr the #of ways that you can affect GH release.

• Ex: to incr GH secretion, you can either incr GHRH or decr GHIH.
• Like cortisol, GH = diurnal pattern of secretion.
• In contrast to cortisol secretion, GH reaches peak levels about an hour after entering deep sleep.

Question 14

True ot false: negative-feedback loops participate in the regulation of GH secretion.

Answer 14

True

*Look at diagram pg 7 of Section 6

Question 15

What are some other factors that can incr the release of GH?

Answer 15

Other factors that can

incr the release of GH = exercise, stress, low blood glucose, and high blood AAs.

Question 16

What can occur as a result of GH deficiency?

Answer 16

GH deficiency can be the consequence of dysfunction either at the level of the hypothalamus, the pituitary, or even at the tissue level.

What’s important is timing
- Dwarfism -> if
there’s a deficiency of GH during childhood, then this is the result, since GH is necessary for full growth potential.
• Can be treated w/ GH if detected early enough.
- Laron dwarfism -> caused by the lack of
response from tissues to GH.
• It responds to IGF-I treatment.
- GH deficiency in adults has less symptoms, but those affected can experience reduced
skeletal muscle mass and strength, decr bone density, and an incr risk of developing HF.

Question 17

What can occur as a result of GH excess?

Answer 17

It’s typically caused by a tumour in the anterior pituitary.

Like GH deficiency, the effects of GH excess are dependent upon when it occurs.
- If it were to occur in childhood, it would have a pronounced effect on the epiphyseal plates = causing rapid growth and producing what is known as gigantism.
- If it were to occur after epiphyseal plate closure then height is not affected. • However, bones can still thicken and cause the condition of acromegaly (characterized by a marked coarsening of the jaw and cheekbones, the
hands and feet enlarge, and the fingers and toes become very thickened).

Question 18

What is the importance of Ca in the human body in regards to growth?

Answer 18

Ca is the most abundant and highly regulated mineral in the human body.

It acts as an electrolyte and is vital to the health of the muscular, circulatory, and digestive systems.

It’s indispensable to the building of bone, and supports the synthesis and function of blood cells.

Question 19

Calcium within the human body is divided into three pools. Predict the percentage of calcium stored by each calcium pool.

• Extracellular calcium
• Calcium in the bone matrix
• Intracellular calcium

99% =

0. 9% =
1. 1% =

Answer 19

99% = Calcium in the bone matrix

0. 9% = Intracellular calcium
1. 1% = Extracellular calcium

Question 20

Which of the following statements about the physiological process that involve calcium are true?

1. Neuromuscular excitability
2. Secretion of vesicles
3. Immune system activation
4. Excitation-contraction coupling in cardiac and smooth muscles
5. Release of neurotransmitters
6. Gas exchange
7. Role as a second messenger

Answer 20

1. Neuromuscular excitability
2. Secretion of vesicles
3. Excitation-contraction coupling in cardiac and smooth muscles
4. Release of neurotransmitters
5. Role as a second messenger

Question 21

How does the parathyroid hormone (PTH) regulate plasma Ca?

Answer 21

Secreted by parathyroid glands. Removing this gland causes death due to hypocalcemia in a few days.

Primary action = incr plasma Ca levels by its effects on bone, the kidneys and intestines

Effect on the bones
- Primary storage of Ca = within the bones, where it’s stored as hydroxyapatite crystals, which essentially is precipitated Ca3(PO4)2.
- The constant remodelling of the bone allows for very rapid changes in free Ca just
by regulating the activity of these cells.
- Osteoclast activity = slightly enhanced
- Osteoblast activity = slightly inhibited
- This means there’s more breakdown of bone than
build up.
- The incr in plasma Ca by PTH is the intended effect, but, the incr in PO4 isn’t.

Effect on kidneys
- PTH stimulates the reabsorption of Ca. W/o this, the body would be forced to keep degrading bone to maintain plasma Ca levels.
- It also stimulates
the kidneys to remove PO4. Important b/c as high levels of plasma PO4 levels cause bone to incr hydroxyapatite precipitation, which would further remove Ca from the plasma.
- It also stimulates the kidneys to activate vitamin D.

~ Review regulation of PTH release slide 14 ~

Question 22

How does calcitonin regulate plasma Ca?

Answer 22

The actions of calcitonin are opposite to those of PTH.
- Calcitonin is secreted in
response to incr plasma Ca levels.

Calcitonin acts on osteoclasts to decr their activity, which prevents the release of Ca and PO4
from the bone.

~ Review negative feedback slide 15 ~

Question 23

How does vitamin D regulate plasma Ca?

Answer 23

It’s properly called cholecalciferol.

This vitamin is further hydroxylated by the kidneys to form calcitriol (the biologically active form of vitamin D).

Vit D functions as a hormone as it can be produced by the skin.
- Using cholesterol as a precursor, the actions of UV light on the skin causes the formation of 7-dehydrocholesterol.
- In colder climates, we don’t have daily skin exposure to sunlight, so
the majority of our vitamin D comes from dietary supplements.

The main function of vitamin D is to incr the intestinal absorption of Ca
- Dietary Ca is not
freely absorbed and w/o vitamin D, dietary Ca is excreted in the feces. Vitamin D also incr
the responsiveness of bone cells to PTH.

Question 24

Regardless of whether the precursors come from the diet or from the skin, vitamin D needs to become
activated by two sequential steps. What are they?

Answer 24

The first step occurs in the liver.

The second step occurs in the kidneys, and each step adds a hydroxyl group to the compound.

PTH plays a role in its formation by stimulating the enzymes in the kidney.
- The end result is the
formation of 1,25-(O H)2-vitamin D3 (also called calcitriol), which is the active form.
- PTH and vitamin D work together in Ca homeostasis, although it is PTH that plays the primary role.

~ Review chart on slides 17 and 18 ~

The most dramatic effect of activated vitamin D is to increase Ca absorption in the intestine since it’s not indiscriminately absorbed by the digestive system.

• When needed, more dietary Ca is absorbed into the plasma under the influence of vitamin D.
• The active form of vitamin D also incr intestinal absorption.
• It also incr the responsiveness of bone to PTH.
• Vitamin D and PTH = closely interdependent.