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BS II, Module III > Mineral Homeostasis > Flashcards

Mineral Homeostasis Flashcards

1
Q

Bones
• 99% of the ____ in our bodies is found in our bones which serve as a reservoir for Ca2+ storage.
• ____% of total adult bone mass turns over each year during remodeling process
• During growth, rate of bone formation exceeds resorption and skeletal mass increases.
• ____ growth occurs at epiphyseal plates.
• Increase in width occurs at ____
• Once adult bone mass is achieved, equal rates of formation and resorption maintain bone mass until age of about ____ years when rate of resportion begins to exceed formation and bone mass slowly decreases.

A 
calcium
10
linear
periosteum
30
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2
Q
  • There are 3 major types of bone cells:
  • ____are the differentiated bone forming cells and secrete bone matrix on which Ca2+ and PO43- precipitate.
  • ____, the mature bone cells are enclosed in bone matrix.
  • Osteoclasts is a large ____ cell derived from ____ whose function is to resorb bone.
A

osteoblasts
osteocytes
multinucleated
monocytes

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3
Q

Bone Formation and Mineralization
• Active ____ synthesize and extrude collagen
• Collagen fibrils form arrays of an organic matrix called the ____.
• ____ is deposited in the osteoid and becomes mineralized
• Dependent on ____
• Alkaline phosphatase and osteocalcin play roles in
bone formation
• Their ____ levels are indicators of osteoblast activity.

A 
osteoblasts
osteoid
calcium phosphate
vitamin D
plasma
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4
Q

How does bone transfer calcium? -Canaliculi

• Within each bone unit, there are fluid-containing channels called the ____.
• Canaliculi traverse the mineralized bone.
• Interior osteocytes remain connected to surface
cells via syncytial ____.
• This process permits transfer of calcium from enormous surface area of the interior to extracellular fluid.

A

canaliculi

cell processes

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5
Q

Control of Bone Formation and Resorption

  • Bone resorption of Ca2+ by two mechanisms: ____ is a rapid and transient effect and ____ which is slow and sustained.
  • Bone formation and resorption are ____ by PTH.
A

osteocytic osteolysis
osteoclastic resorption
stimulated

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6
Q

Osteocytic Osteolysis
• Transfer of ____ from canaliculi to extracellular fluid via activity of osteocytes.
• Does not decrease ____.
• Removes calcium from most ____ formed crystals
• Happens ____.

A

calcium
bone mass
recently
quickly

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7
Q

Bone Resorption
• Does not merely extract calcium, it ____ entire matrix of bone and ____ bone mass.
• Cell responsible for resorption is the osteoclast.

A

destroys

diminishes

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8
Q

How to maintain mineral homeostasis?

  • Build and maintain a healthy skeleton and dentition
  • Maintain the ____ and intracellular ____ at a fixed level
  • Maintain cellular and extracellular [PO4 ]
  • Prevent ____ calcification

The mechanisms of mineral homeostasis are designed to satisfy all these needs

A

blood
[Ca++]
ectopic

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9
Q

Mineral homeostasis

  • Adult organisms try to maintain ____ (intake = output)
  • Calcium and phosphate ions can combine to form insoluble salts, the concentrations of these ions in cells and body fluids is precisely regulated to prevent inappropriate precipitation
  • Mineral balance is achieved by ____ control of Ca and P transport into and out of ____, ____ and ____
A 
mineral balance
hormonal
intestine
kidney
bone
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10
Q

Why is Calcium important?

  • Ca salts in bone provide structural integrity of the skeleton.
  • ____ is the most abundant mineral in the body.
  • The amount of Ca is balanced among intake, storage, and excretion.
  • This balance is controlled by transfer of Ca among 3 organs: ____, ____, ____.

• Ca ions in extracellular and cellular fluids is essential to normal function of a host of biochemical processes
ü Neuoromuscular excitability and signal transduction
ü ____ coagulation
ü Hormonal secretion
ü ____ regulation
ü Neuron excitation

A 
Calcium
intestine
bone
kidneys
blood
enzymatic
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11
Q

Intake of Calcium
• About ____ mg of Ca is ingested per day.
• About ____ mg of this is absorbed into the body.
• Absorption occurs in the ____, and requires ____ (stay tuned….)

A

1000
200
small intestine
vitamin D

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12
Q

Storage of Calcium

  • An adult human contains ~ ____ g of Ca++
  • ~ ____% is in the skeleton in the form of hydroxyapatite Ca10(PO4)6(OH)2 and ____% is in blood and body fluids intracellular calcium
  • Extracellular Ca++ concentration is ~ ____ (~10 mg/dL)
  • The concentration of Ca2+ in the cytosol is ~ ____

• This ____ concentration gradient across the plasma membrane has important biological implications

A 
1000
99
1
10-3 M
10-7 M
steep
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13
Q

Regulation of Calcium

  • The important role that calcium plays in so many processes dictates that its ____, both extracellularly and intracellularly, be maintained within a very ____ range.
  • This is achieved by an elaborate system of controls
A

concentration

narrow

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14
Q


Regulation of Intracellular Calcium

  • Control of cellular Ca homeostasis is as carefully maintained as in extracellular fluids
  • [Ca2+]cyt is approximately ____ of extracellular concentration
  • Stored in ____ and ____
  • ____ transport systems control [Ca2+]cyt
  • Calcium ____ into cytosolic compartment and is actively pumped into storage sites in organelles to shift it away
A 
1/1000th
ER
mitochondria
"pump-leak"
leaks
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15
Q

Extracellular Calcium
•Ca2+ normally ranges from ____ mg/dL in the plasma.
• Three definable fractions of calcium in serum:
• Ionized calcium 50% (Only free, ionized Ca2+ is
biologically ____).
• Protein-bound calcium 40%
—• 90% bound to ____
—• Remainder bound to ____
• Calcium complexed to serum constituents 10%
—____ and ____

A 
8.5-10
active
albumin
globulins
citrate
phosphate
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16
Q

Intake of Phosphate
• About ____ mg of phosphate is ingested per day.
• About ____ mg of this is absorbed into the body.
• Phosphate is absorped in the ____, stored in the ____ and excreted by the ____

A 
1000
450
small intestine
skeleton
kidneys
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17
Q

Storage of Phosphate

• An adult human contains approximately ____ g of phosphorus
- ~ ____% of this is present in crystalline form in the skeleton
- ~ ____% is present in the extracellular fluids (~ 1 mM)
- The concentration in cells is ~ ____ mM
• These concentrations are ____ rigidly maintained than that of calcium

A 
700
85
15
5
less
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18
Q

Phosphorous in Blood and Bone

  • PO4 normal plasma concentration is ____ mg/dL. 87% is ____, with 35% complexed to different ions and 52% ____.
  • 13% is in a ____ protein bound state. 85- 90% is found in bone.
  • The rest is in ATP, cAMP, and proteins
A

3.0-4.5
diffusible
ionized
non-diffusible

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19
Q

Regulation of Pi homeostasis

  • Cells require adequate Pi for energy metabolism and nucleic acid synthesis
  • Cells take up Pi from the blood using ____ (____ transport)
  • Absorption and reabsorption of Pi occur primarily in the ____ and ____
  • Pi is regulated by ____, ____ and ____
A 
Na/Pi co-transporters
active
intestine
kidney
PTH
vitamin D
FGF23
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20
Q

Hormonal Control of Ca2+

• The major hormones involved in plasma calcium homeostasis are:
ü 1,25(OH)2 vitamin D3 acts on ____, ____ and ____

ü Parathyroid hormone (PTH) acts on ____ and ____

ü Calcitonin (CT) acts ____ and ____
• Vitamin D and PTH ____ blood calcium
• CT ____ blood calcium.
• Many other hormones effect calcium homeostasis

A

intestine
kidney
bone

kidney
bone

bone
kidney

increase
decreases

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21
Q

Vitamin D

Vitamin D is the precursor of the hormone 1,25(OH)2 vitamin D3, one of the hormones controlling mineral metabolism

• Two natural forms of Vitamin D:
- ____, derived from the plant steroid ergosterol = ____
- ____, derived from cholesterol = ____
• Both forms must be further ____ to be effective 1,25-(OH)2-vitamin D.
• Dietary Vitamin D is usually ____.

A 
vitamin D2
ergocalciferol
vitamin D3
cholecalciferol
hydroxylated
D2
22
Q

Vitamin D action
v The active form of Vitamin D, 1,25(OH)2-D3, is synthesized in the ____

v The rate of this conversion is controlled by ____

v The major target organs for 1,25(OH)2-D3 are
____, ____ and ____

v Increased levels of 1,25-(OH)2-D lead to:
• Increased Ca++ and Pi absorption by ____
• Increased Ca++ reabsorption in ____
• Increased resorption of ____
• Similar to effects of PTH

A 
kidney
PTH
intestine
kidney
bone
small intestine
kidney
bone
23
Q

What do the range of serum 25OH vitamin D conincide with?

< 30 nmol/L, < 12 ng/mL = ____
>= 50 nmol/L, >=20 ng/mL = ____
> 125 nmol/L, >50 ng/mL = ____

A

vitamin D deficincey
considered healthy and adequate bone health
adverse effects

24
Q

Look up the target genes of vitamin D

Know this table!

A

OKAY

25
Q

Mechanism of vitamin D action

• The vitamin D receptor (VDR) belongs to the ____ hormone receptor superfamily
• The VDR binds cooperatively to these vitamin D response elements (VDREs) as a ____ with another member of the family, the ____

A

steroid/thyroid
heterodimer
retinoid X receptor (RXR)

26
Q 
Vitamin D-dependent Ca2+ Absorption
• \_\_\_\_>\_\_\_\_>\_\_\_\_
• Absorption is greater at \_\_\_\_ pH
• The pH of the stomach is about 2
• Peak absorption at the beginning of the \_\_\_\_
A 
dudenum
jejunum
ileum
low
duodenum
27
Q

Vitamin D action

  • The main action of 1,25-(OH)2-D is to ____ absorption of Ca2+ from the intestine.
  • 1,25-(OH)2-D induces the production of ____ proteins which sequester Ca2+, buffer high Ca2+ concentrations that arise during initial absorption and allow Ca2+ to be absorbed against a high Ca2+ gradient
A

calcium binding

28
Q

Vitamin D Actions on Bones

  • Another important target for 1,25-(OH)2-D is the ____.
  • ____, but not ____ have vitamin D receptors.
  • In its absence, excess ____ accumulates from lack of 1,25-(OH)2-D repression of osteoblastic collagen synthesis.
  • 1,25-(OH)2-D acts on osteoblasts which produce a ____ signal that activates osteoclasts to resorb ____ from the bone matrix.
  • 1,25-(OH)2-D also stimulates ____.
A 
bone
osteoblasts
osteoclasts
osteoid
paracrine
Ca2+
osteocytic osteolysis
29
Q

What factor(s) regulate Vitamin D?

  • PTH increases ____ activity, increasing production of active form.
  • This increases calcium ____ from the intestines, increases calcium ____ from bone, and ____ loss of calcium through the kidney.
  • As a result, PTH secretion ____, decreasing 1- hydroxylase activity (negative feedback).

• Low ____ concentrations also increase 1- hydroxylase activity (vitamin D increases phosphate reabsorption from the ____).

A 
1-hydroxylase
absorption
release
decreases
decreases
phosphate
urine
30
Q

Vitamin D deficiency caused skeletal diseases

• Vitamin D-dependent rickets type ____ in children - a softening of bones potentially leading to fractures and deformity (defective mineralization or calcification of bones)
• ____ – adult form of rickets
• Vitamin D-resistant rickets (mutation in ____)
- Hypophosphatemic rickets – hereditary disease of ____ metabolism (____ mutation)
- Pseudo-deficiency rickets – genetic defects in ____ metabolism (CYP27B1 ____ of function)

A 
II
oseomalacia
VDR
phosphate
PHEX
vitamin D
loss
31
Q

Parathyroid hormone
• PTH is an 84 amino acid monomeric polypeptide hormone
• Only the first ____ amino acids are essential for activity
• A related hormone, PTHrP (PTH-related peptide),
• has significant ____ to PTH

A

34

homology

32
Q

Parathyroid Hormone

  • PTH is synthesized and secreted by the ____ which lie ____ to the thyroid glands.
  • The blood supply to the parathyroid glands is from the ____ arteries.
  • The ____ in the parathyroid gland are the principal site of PTH synthesis.
  • It is THE MAJOR of ____ homeostasis in humans.
A 
parathyroid gland
posterior
thyroid
chief cells
Ca++
33
Q

Actions of PTH

  • Fine tunes Ca2+ levels in blood
  • – ____ Ca2+
  • – ____ Pi
  • PTH acts directly on ____ to stimulate resorption and release of Ca2+ into the extracell space (____)
  • – Gs protein-coupled receptors in osteoblasts increase ____ and activate ____
  • – ____ osteoblast function
  • – occurs when PTH is secreted ____; the opposite occurs when it is given ____ by injection
A 
increases
bone
slow
cAMP
PKA
inhibits
continuously
once daily
34
Q

Actions of PTH

  • Two effects in kidney
    • PTH acts directly on kidney to ____ calcium reabsorption and phosphate excretion (____)
  • – Gs protein-coupled receptors
  • – PTH acts on ____
  • – Calcitonin ____
  • Stimulate transcription of ____ for vitamin D activation in kidney
  • – Vitamin D ____ calcium and phosphate absorption
A

kidney
rapid
distal tube
inhibits

1-alpha hydroxylase
increases

35
Q

Parathyroid hormone receptor PTH1R

• Highly Expressed in ____ and ____.
• Also exressioned in many other tissues, particularly
in growth plate ____
• In tissues other than kidney and bone, PTH1R mediates the paracrine/autocrine actions of ____, rather than the endocrine actions of ____

A 
kidney
bone
chondrocytes
PTHrP
PTH
36
Q

The PTH paradox

  • Recent evidence shows that PTH can also have an ____ effect on bone
  • The choice between anabolic and catabolic effects of the hormone depends on the ____ of hormone application
  • ____ administration of PTH may be useful in the treatment of osteoporosis and periodontal disease
A

anabolic
kinetics
intermittent

37
Q

How is PTH regulated?
• The dominant regulator of PTH is ____.
• Secretion of PTH is ____ related to [Ca2+].
• Maximum secretion of PTH occurs at plasma Ca2+ below ____ mg/dL.
• At Ca2+ above ____ mg/dL, PTH secretion is maximally inhibited.

A

plasma Ca2+
inversely
3.5
5.5

38
Q

Calcium-sensing receptor

  • The CaSR is a cell surface ____ capable of detecting small changes in serum [Ca2+]
  • CaSR is also expressed in ____, chondrocytes, and ____
A

GPCR
kidney tubules
osteoblasts

39
Q 
Calcitonin
• Product of \_\_\_\_ cells of the thyroid
• 32 aa
• \_\_\_\_ osteoclast mediated bone resorption
• This \_\_\_\_ serum Ca2+
• Promotes renal \_\_\_\_ of Ca2+
A

parafollicular C
inhibits
decreases
excretion

40
Q

Calcitonin
• The major stimulus of calcitonin secretion is a rise in ____ levels
• Calcitonin is a physiological ____ to PTH with regard to Ca2+ homeostasis
• The target cell for calcitonin is the ____.
• Calcitonin acts via increased ____ concentrations to inhibit osteoclast motility and cell shape and inactivates them, resulting in decreased bone resorption.
• The major effect of calcitonin administration is a rapid ____ in Ca2+ caused by inhibition of bone resorption.

A 
plasma Ca2+
antagonist
osteoclast
cAMP
fall
41
Q


Influences of Growth Hormone

  • Normal GH levels are required for skeletal growth.
  • GH increases intestinal ____ absorption and renal ____ resorption.
  • Insufficient GH prevents normal bone production.
  • Excessive GH results in bone abnormalities (____ of bone formation AND ____).
A

calcium
phosphate
acceleration
resorption

42
Q

Effects of Glucocorticoids
• Normal levels of glucocorticoids (____) are necessary for skeletal growth.
• Excess glucocorticoid levels ____ renal calcium reabsorption, interfere with intestinal calcium ____, and ____ PTH secretion.
• High glucocorticoid levels also interfere with ____ production and action, and ____ production.
• Net Result: rapid ____

A 
cortisol
decrease
absorption
stimulate
growth hormone
gonadal steroid
osteoporosis (bone loss)
43
Q

Influence of Thyroid Hormones

  • Thyroid hormones are important in skeletal growth during ____ and ____ (____ effects on osteoblasts).
  • Hypothyroidism leads to ____ bone growth.
  • Hyperthyroidism can lead to ____ bone loss, suppression of ____, decreased ____ metabolism, decreased ____ absorption. Leads to ____.
A 
infancy
childhood
direct
decreased
increased
PTH
vitamin D
calcium
osteoporosis
44
Q

Effects of diets

  • ____ are essential nutrients which cannot be made by the body, so they need to be ingested.
  • Increasing dietary intake of Ca may prevent osteoporosis in ____ women.
  • Excessive ____ intake in diet can impair renal Ca reabsorption, resulting in ____ blood Ca and ____ PTH release. Normally, PTH results in increased absorption of Ca from the GI tract (via vitamin D). But in aging women, vitamin D production decreases, so Ca isn’t absorbed, and PTH instead causes increased ____.
A 
biominerals
postmenopausal
Na
lower
increased
bone loss
45
Q

Effects of diets

  • High ____ diet may cause loss of Ca from bone, due to acidic environment resulting from ____ metabolism and decreased reabsorption at the kidney.
  • Intake of carbonated beverages has been associated with ____ excretion and loss of ____
A

protein
protein
increased
calcium

46
Q

Effects of Exercise

  • Bone cells respond to ____ gradients in laying down bone.
  • Lack of weight-bearing exercise decreases bone ____, while increased exercise helps form ____.
  • Increased bone resorption during immobilization may result in ____
A

pressure
formation
bone
hypercalcemia

47
Q 
Disorders of bone mineral homeostasis
• \_\_\_\_-senile, postmenopausal 
• Chronic \_\_\_\_ failure
• Primary hyperparathyroidism
• Hypoparathyroidism
• \_\_\_\_- nutritional vitamin D dependent, vitamin D resistant 
• \_\_\_\_ osteodystrophy
• Hypercalcemia/hypocalcemia
•Hyperphosphatemia/hypophosphatemia
• Idopathic hypercalciuria 
• \_\_\_\_ disease
A 
osteoporosis
renal
rickets
intestinal
pagets
48
Q

Osteoporosis
• Osteoporosis is characterized by a significant ____ in bone mineral density compared with age- and sex-matched norms
• There is a decrease in both bone ____ and bone ____
• Osteoporosis is the most ____ metabolic bone disease
• Affects 20 million Americans and leads to 1.3 million fractures in the US per year
• Women lose 50% of their trabecular bone and 30 % of their cortical bone
• 30% of all ____ women will sustain an osteoporotic fracture as will 1/6th of all men
• The cost of health care and lost productivity is $14 billion in the US annually


A 
reduction
mineral
matrix
common
postmenapausal
49
Q

Vitamin D Deficiency: Rickets

  • Inadequate intake and absence of ____
  • The most prominent clinical effect of Vitamin D deficiency is ____, or the defective mineralization of the bone matrix
  • Vitamin D deficiency in children produces ____
  • A deficiency of renal 1α-hydroxylase produces ____ rickets
  • Sex linked gene on the ____ chromosome
  • Renal tubular defect of ____ resorption
  • Teeth may be ____ and eruption may be ____
A 
sunlight
osteomalacia
rickets
vitamin D-resistant
X
phosphate
hypoplastic
retarded
50
Q

Rickets

•Thining (____) or decreased mineralization (____) of the enamal
•____ teeth
•Minimal caries can produce ____; periapical abscesses are thus common

A

hypoplasia
hypocalcification
hypoplastic
pulpitis

BS II, Module III (12 decks)

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