Feb 25th Flashcards
99% of calcium is found in
Bones
- stably stored as hydroxyapatite
- calcium salts + phosphate provide structural integrity
1 % of calcium is found in soft tissues
- intracellular (0.9%)
- extracellular (0.1%)
extracellular calcium
- very tightly regulated
- 50% ionized (free)
- 40% protein-bound
- 10% complexed with phosphate & citrate
- extracellular fluid/plasma
- bone
intracellular calcium
- also highly regulated
- more abundant than extracellular
- largely associated with membranes in mitochondria, endoplasmic reticulum, & plasma membrane
intake vs output (calcium)
intake = diet
- 1/3 absorbed in small intestine
- absorption is hormone regulated
- recommended 1000mg/day
output = kidney
- body can’t make it s it has to be replaced
3 hormones regulate movement of calcium between bone, kidneys, and intestine
- parathyroid hormone (PTH)
- Calcitrol (vitamin D3)
- Calcitonin
1&2 most important in adults
What is the function of PTH?
Regulates blood calcium by increasing bone resorption, kidney reabsorption, and intestinal absorption.
Why can the thyroid be removed but not the parathyroid glands?
Parathyroid glands are essential for life because PTH is critical for calcium homeostasis.
How does PTH increase calcium levels?
Stimulates bone resorption, kidney reabsorption, and vitamin D activation (which increases gut absorption of calcium).
Where are the parathyroid glands first seen in evolution?
In terrestrial amphibians.
2 cell types in parathyroid glands
- Chief cells -produce PTH
- Oxyphils - function unknown
When plasma Ca2+ begins to fall, PTH acts to raise blood Ca2+ back to normal
via 3 mechanisms
- Stimulates osteoclasts to resorb bone (primary mechanism)
- Stimulates kidneys to resorb Ca2+
- Stimulates kidneys to produce enzyme needed to activate vitamin D,
which promotes better absorption of Ca2+ from food/drink across
intestinal epithelium
hypocalcaemia
- too low
- increased PTH secretion - stimulates resorption to get more calcium back into the blood
hypercalcaemia
- too high
- decreased PTH secretion
What is bone constantly doing?
Being formed and resorbed
What does bone contain?
Calcified extracellular matrix (ECM) that forms when calcium phosphate crystals precipitate & attach to a lattice support
What is the most common form of calcium phosphate in bone?
Hydroxyapatite
In what form is most Ca²⁺ found in bone?
Crystallized (as hydroxyapatite)
Is all calcium in bone crystallized?
No, a small fraction is ionized and readily exchangeable.
Bone deposition
- osteoblasts
- secrete a matrix of collagen protein, which becomes hardened by deposits of hydroxyapatite
bone resorption
- osteoclasts dissolve hydroxyapatite & return the bone calcium (& phosphate) to the blood
What does PTH stimulate the kidneys to do?
Resorb Ca²⁺ and produce 1-α-hydroxylase enzyme
What is the role of 1-α-hydroxylase?
Activates vitamin D (by converting it to its active form, calcitriol).
What does active vitamin D (calcitriol) do?
Increases Ca²⁺ absorption in the intestines.
How does vitamin D3 affect calcium levels?
Acts on intestines to absorb more Ca²⁺ from food and drink.
vitamin D synthesis
- vitamin D3 produced from its precursor molecule, 7-dehydrocholesterol
under the influence of
UVB sunlight - Vitamin D3 secreted
into blood from
skin/intestine (functions
as a pre-hormone i.e.
inactive) - Goes to liver & is
chemically changed
(hydroxyl group added
to C25) - Requires hydroxyl
group addition to C1
to become active
(done by enzyme in
kidneys that is
stimulated by PTH)
where does a person get most of their vitamin D
production of vitamin D in the skin
calcitonin
- made in C cells of thyroid in response to high calcium
- minor role in adult humans
What controls phosphate metabolism?
The same mechanisms that regulate Ca²⁺ metabolism.
Is phosphate metabolism as tightly regulated as calcium metabolism?
No, it is not as tightly regulated.
Where does phosphate get returned to or received from?
Bone, kidney filtrate, and the GI tract.
Hyperparathyroidism
- Parathyroid too active
- Hypercalcaemia (too much Ca2+
in blood) - Increased bone resorption
(fractures) - Mineralization of soft tissues
- Increased thirst & urination (Ca2+
blocks ADH effects)
Hypoparathyroidism
- Parathyroid not active enough
- Hypocalcaemia (not enough Ca2+
in blood) - Muscular weakness, ataxia
- Cardiac arrhythmias
vitamin D deficiency in children and adults
children = rickets
- bone pain, stunted growth, deformities
adults = osteomalacia
- bone pain, fractures
Osteoporosis
- Most common disorder of bone
- Reduction of bone quality due to excess absorption
- Risk of bone fractures
- Known risk factors:
- Sex (females,
especially after menopause) - Lack of exercise
- calcium deficient diet
What inhibits GH secretion?
Somatostatin from the hypothalamus.
What stimulates GH secretion?
GHRH (Growth Hormone-Releasing Hormone) from the hypothalamus.
Where is GH secreted from?
The anterior pituitary.
How does GH exert its effects?
Directly or by stimulating the liver to produce somatomedins (e.g., IGF-1).
How is GH secreted throughout the day?
In several large pulses/peaks lasting 10-30 minutes each.
When does the largest GH peak occur?
About 1 hour after sleep onset (circadian rhythm).
What causes sore legs upon waking as a child?
Growth hormone peaks stimulating bone growth.
What does GH stimulate the liver to produce?
Insulin-like Growth Factors (IGF-1, IGF-2).
How similar are IGFs to insulin?
They share 40% homology with insulin.
How is IGF-1 transported in the blood?
Almost entirely bound to transport proteins (IGF-BPs).
Do IGF-1 transport proteins have a function?
Yes, some have an endocrine function, as there are receptors for them.
Can GH stimulate IGF-1 production outside the liver?
Yes, GH stimulates IGF-1 synthesis and release in other tissues too.
Why is it hard to separate GH and IGF-1 effects?
Because GH and IGF-1 can have overlapping functions in tissues.
How do GH and IGF-1 interact in different tissues?
They sometimes exert opposite actions, suggesting independent roles.
What are the primary targets of GH?
Liver, adipose tissue and most tissues
What effect does GH have on the liver?
Stimulates IGF-1 production.
How does GH affect muscle and other organs?
Increases protein synthesis and promotes growth.
How does GH affect adipose tissue?
Stimulates lipolysis, leading to the release of fatty acids.
What does GH do to glucose metabolism in most tissues?
Decreases glucose utilization.
dwarfism
severe GH deficiency in children
gigantism
over secretion of GH in children
Acromegaly
over secretion of GH in adults
Where is growth hormone (GH) produced?
Anterior pituitary gland.
When does GH play its biggest role?
During childhood.
What are the two periods of rapid growth in children?
Postnatal growth and puberty.
How does GH promote soft tissue growth?
By increasing cell size (hypertrophy) and cell number (hyperplasia).
How does bone diameter increase?
Matrix deposits on the outer surface of the bone.
Where does bone length growth occur?
At the epiphyseal plates (near the ends of bones).
What cells are found in the epiphyseal plate?
Chondrocytes (collagen-producing cells).
What happens as the collagen layer thickens?
Old cartilage calcifies, chondrocytes degenerate, and osteoblasts lay bone matrix.
What role does IGF-1 play in bone growth?
It stimulates chondrocyte and osteoblast activity.
Why are cattle treated with synthetic growth hormone (GH)?
To increase milk yield, promote faster growth, and produce leaner meat.
How much does synthetic GH increase milk production in cattle?
30%
What are the potential concerns regarding synthetic GH use in cattle?
Possible adverse effects on reproduction and human health.
