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ENDOCRINE SYSTEM > Hormones In Calcium And Bone Metabolism > Flashcards

Hormones In Calcium And Bone Metabolism Flashcards

1
Q

A normal adult body contains about

A

1kg of Ca

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2
Q

70kg indiv = 1,000g Ca

1% in soft tissues and extracellular fluids
Approx. 99% is present in the skeleton as

A

Hydroxyapatite (Ca10(PO4)6(OH)2)

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3
Q

A normal diet provides how much Ca per day

A

20-2000mg with an ave of 1000mg Ca per day

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4
Q

Approx. How much is absorbed, in majority in ileum bcs of its large absorptive surface

A

300g

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5
Q

Secreted into the intestinal tract in bile, pancreatic juice and intestinal secretions so that the net absorption of Ca equals about

A

175mg/day

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6
Q

The conc of Ca in plasma ave about

A

9.4mg/dL

Normally varying between 9 and 10 mg/dL
This is equivalent to about 2.4mmol of Ca per liter

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7
Q

The Ca present in plasma is present in 3 forms:

A

(1) 40% (1mmol/L) of Ca is combined w the plasma CHONs = nondiffusible form thru capillary mem
(2) 10% Ca (0.2 mmol/L) diffusible thru the cap mem but is combined w other subs of the plasma and interstitial fluids (citrate and phosphate) Not ionized
(3) 50% Ca is both diffusible and ionized (1.2 mmol/L or 2.4 mEq/L) divalent

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8
Q

The skeleton also serves as a storage depot for phosphorus and contains about how much of the total body phosphorus?

A

80%

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9
Q

The plasma conc of total Ca (ionized and non) is about

A

10mg/dL

Equivalent to 5mEq/L or 2.5mmol/L

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10
Q

Ca is present in plasma as

A

A. Ionized or free (45%)
B. Complexed w HPO4^2-, HCO3- or citrate ion (10%)
C. Bound to CHON (45%)

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11
Q

Sum of ionized and complexes Ca constitutes the diffusible fraction (55%) of Ca

A

The protein-bound form constitutes the nondiffusible fraction (45%)

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12
Q

Regulates the serum-ionized Ca conc

A

PTH, Calcitonin, Vit D

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13
Q

Distribution (mmol/L) of Ca in normal human plasma

Total diffusible
Ionized Ca
Complexed to HCO3, Citrate etc

A

Total diffusible = 1.34
Ionized Ca = 1.18
Complexed to HCO3, Citrate etc = 0.16

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14
Q

Total nondiffusible (protein bound)
Bound to albumin
Bound to globulin

A 
Total nondiffusible (protein bound) = 1.16
      Bound to albumin = 0.92
      Bound to globulin = 0.24
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15
Q

Total plasma Ca

A

2.50mmol/L

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16
Q

This represents the Ca pool that is not readily exchangeable and it is not available for rapid mobilization

A

Larger Ca pool

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17
Q

This represents the Ca pool that is readily exchangeable bcs it’s in physiochemical equilibrium w the ECF

The pool consists of Ca phosphate salts and provides an immediate reserve for sudden decreases in bld Ca2+

A

Smaller Ca pool

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18
Q

When the pH of ECF becomes more acidic, there is a

A

Relative increase in H2PO4 and decrease in HPO4-

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19
Q

The ave total quantity of inorganic phosphorus represented by both phosphate ions is

A

4mg/dL

Varying between normal limits of 3-4mg/dL in adults and 4-5mg/dL in children

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20
Q

Total body phosphorus is

A

500-800g (16.1-25.8 mol), 85-90% of wc is in the skeleton

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21
Q

Total plasma phosphorus is abt

A

12 mg/dL

with 2/3 of total in organic compounds and remaining inorganic phosphorus mostly in PO4^3-, HPO4^2- and H2PO4-

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22
Q

When Ca intake is high, 1,25-dihydroxycholecalciferol levels fall bcs of

A

Increased plasma Ca

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23
Q

Relationship of Ca absorption and Ca intake

A

Inverse

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24
Q

Increase absorption

A

Increase CHON diet in adults

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25
Q

Ca absorption is also decreased by subs that form

A

Insoluble salts w Ca (e.g phosphates and oxalates or by alkalis)

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26
Q

Enters the intestines via secreted GI juices and sloughed mucosal cells

A

An additional 250mg/day of Ca

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27
Q

How much of daily intake of Ca is excreted in the feces

A

90% (900mg/day)

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28
Q

Pi is absorbed in the duodenum and small intestine by

A

Active transport and passive diffusion

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29
Q

It is linearly proportionate to dietary intake

A

Absorption of Pi

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30
Q

Ingested Ca excreted in urine

A

10% or 100mg/day

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31
Q

How many percent of plasma Ca is bound to plasma proteins and not filtered by the glomerular capillaries, the rest is combine d w anions s/a phosphate (9%) or ionized (50%) and is filtered thru the glomeruli into tye renal tubules

A

41%

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32
Q

Amount of phosphorus normally entering bone is about

A

3mg (97 umol/kg/d), w an equal amt leaving via reabsorption

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33
Q

% if filtered Pi us reabsorbed

A

85-90%

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34
Q

Proximal tubule accounts for most of the reabsorption, and is inhibited by PTH

A

Active transport

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35
Q

Renal phosphate excretion is ctrlled by an overflow mechanism this is when

A

Phosphate conc in plasma is below the critical value of abt 1mmol/L

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36
Q

The rate of phosphate loss is directly proportional to the additional increase thus kidneys regulate the phosphate conc in ECF by altering rate of phosphate excretion

A

Above critical conc

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37
Q

Ca doesn’t require an active transport process bcs the conc gradient across the membrane is

A

larger for Ca than for any other ion

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38
Q

Ca conc in ICF is

A

10-70 mmol/L

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39
Q

Ca in ECF is

A

10^-3 mol/L (actual value is 2.5x10^-3 mol/L)

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40
Q

The Ca gradient from outside to inside the cell is on the order of

A

10,000 to 1

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41
Q

Ca is bound to cell surfaces and has a role in

A

Stabilization of membrane and intracellular adhesion

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42
Q

Chronic hypocalcemia or hypophosphatemia greatly decreases

A

Bone mineralization

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43
Q

Causes NS excitement and tetany

- increase neuronal mem permeability to Na, easy action potentials

A

Hypocalcemia

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44
Q

At plasma Ca conc about 50% below normal, the peripheral nerve fibers become so excitable that they begin to

A

Discharge spontaneously

Elicit tetanic muscle contraction

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45
Q

Tetany in hand

Occurs before tetany in other body parts develop

A

Carpopedal spasm

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46
Q

Occurs when bld conc of Ca falls from its normal lvl of 9.4mg/dL wc is only 35% below normal Ca conc and usually lethal at about 4mg/dL

A

Tetany

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47
Q

When lvl of Ca in body fluids rises above normal, the ND depress and reflex are sluggish

A

Decrease QT interval
Lack appetite
Constipation
Depressed contractility of muscle walls of GI

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48
Q

Depressive effects begin to appear when the blood Ca rises above

A

12mg/dL

Marked: 15mg/dL

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49
Q

Ca rises above ___ in bld, Ca phos crystals ppt

A

17mg/dL

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50
Q

Exchangeable Ca salts in bones are

A

Amorphous Ca phos compounds

- mainly CaHPO4

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51
Q

The quantity of these salts that is available for exchange is abt 0.5 to 1% of the tCa salts of the bone

A

Total of 5-10g Ca

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52
Q

Within 3-5 mins after an cute increase in Ca ion conc, the rate of PTH secretion

A

Decreases

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53
Q

Relationship of PTH and Calcitonin

A

Inverse

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54
Q

Causes rapid deposition of Ca in bones

A

Inc in Calcitonin

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55
Q

Can cause a high Ca conc to return to normal perhaps considerably more rapidly than can be achieved by the exchangeable Ca-buffering mechanism alone

A

Excess Ca

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56
Q

Ca regulation involves 3 tissues, 3 hormones and 3 cell types

A

3 tissues: bone, intestine, kidney
3 hormones: PTH, calcitonin, activated vit D3
3 cell types: osteoblasts, osteocytes, osteoclasts

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57
Q

When plasma Ca falls

A

PTH secretion increases

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58
Q

Hypercalcemic hormone

A

PTH

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59
Q

Hypocalcemic hormone

A

Calcitonin

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60
Q

A 32 AA residue polypeptide secreted by the parafollicular (C) cells of thyroid gland

A

Calcitonin

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61
Q

As plasma Ca increases

A

Calcitonin secretion increases

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62
Q

Calcitonin release is stimulated by

A

Pentagastrin

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63
Q

A secosteroid containing 27 C atoms wc makes it the largest steroid hormone

A

Vit D3 (cholecalciferol)

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64
Q

The major bld form of vit D

Prevent rickets

A

Calcidiol (25-hydroxyvitamin D3) 25-hydroxycholecalciferol

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65
Q

Another active metabolite of vit D

On a molar basis, it is 100x more potent than calcidiol

A

Calcitriol (1,25-dihydroxyvitamin D3) 25-dihydroxycholecalciferol

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66
Q

Inhibits bone resorption and increases the amount of Ca in urine

A

Calcitonin

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67
Q

Acts on one of the PTH receptors and is important in skeletal dev in the uterus

A

PTHrP

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68
Q

lower plasma Ca lvls by inhibiting osteoclast formation and activity but over long pds they cause osteoporosis by decreasing bone formation and increasing bone resorption

A

Glucocorticoids

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69
Q

They decrease bone formation by

A

inhibiting protein synthesis in osteoblasts

they decrease absorption of Ca and PO4^3- from the intestine and increase the renal excretion of these increases the secretion of ions

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70
Q

Increases Ca excretion in the U but it also increases intestinal reabsorption of Ca and this effect may be greater than the effect on excretion w a resultant positive Ca balance

A

GH

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71
Q

generated by the action of GH stimulates CHON synthesis in the bone

A

IGF-I

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72
Q

may cause hypercalcemia, hypercalciuria and sometimes osteoporosis

A

Thyroid hormone

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73
Q

prevents osteoporosis probably by direct effect on the osteoblasts

A

estrogen

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74
Q

increases bone formation and there is significant bone loss in untreated diabetes

A

Insulin

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75
Q

is found in the form of hydroxyapatite crystals

A

Bone Ca

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76
Q

The empirical chemical formula for this substance is Ca10(PO4)6(OH)2 or {(ICa3PO4)2}3

A

Hydroxyapatite crystals

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77
Q

Fluoride ion can replace the OH- group and form

A

fluoroapatite {(Ca3PO4)2}3 CaF2

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78
Q

Ca:Phos ratio in bone is

A

1.7:1

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79
Q

A large SA is provided by the microcrystalline structure of bone; it is estimated to be

A

100 acres in human

80
Q

over 90% of organic matrix is

81
Q

bone is composed of tough organic matrix that is grealy strengthened by

A

deposits of Ca salts

82
Q

early dev, bone exists as

A

osteoid - an organic, unmineralized matrix surrounding the bone cells that deposited it

83
Q

embryonic germ layer that gives rise to cartilage, bone and muscle

84
Q

can differentiate as bone cells including:

  1. cells that deposit dentin in teeth
  2. cartilage and bone of the head
A

Neural crest cells

85
Q

are highly differentiated cells that nonmitotic in their differentiated state

A

osteoblasts

  • secrete and synthesize collagen
  • cont abundant alk phos
  • derived fr BM mesenchyme
86
Q

become buried in bone matrix
has osteolytic activity
no longer syn collagen

A

osteocytes

87
Q

large, multinucleated cells containing numerous lysosomes
they mediate bone resorption at bone surfaces
contain acid phos
are stimulated by PTH and form significant amounts of lactic and hyaluronic acids

A

osteoclasts

88
Q

Might cause bone dissolution via an increased local conc of H+ wc solubilizes bone mineral and increases the activity of enz that degrade matrix

Derived from circulating monocytes

A

Osteoclasts

89
Q

Stimulate osteoblasts

A 
PTH
1,25-dihydroxycholecalciferol
IL-1
T3, T4
HGH, IGF-1
PGE2
TNF
Estrogen
90
Q

Inhibit osteoblasts

A

Corticosteroids

91
Q

Stimulate osteoclasts

A

PTH
1,25-dihyxycholecalciferol
IL-6, IL-11

92
Q

Inhibit osteoclasts

A 
Calcitonin
Estrogen (by inhibiting production of certain cytokines)
TGF-B
IFN-a
PGE2
93
Q

Arise from the fourth brachial/pharyngeal pouch in conjunction w the ultimobrachial bodies

A

Superior parathyroid glands

94
Q

Arise from the third brachial/pharyngeal pouches in conjunction w the thymus

A

Inferior parathyroid glands

95
Q

Are more constant in position and lie at the level of the middle of the posterior border of the thyroid gland

A

Superior parathyroid glands

96
Q

Close proximity to the cricothyroid membrane, entrance of the recurrent laryngeal nerve and usually cephalad to the

A

Superior thyroid glands

97
Q

Variable in location than the superior glands

2cm in diameter centered on point that is on the posterolateral aspect of the lower pole of thyroid glands

A

Two inferior parathyroid glands

98
Q

Removal of half the parathyroid glands usually causes

A

No major physiologic abnormalities

99
Q

However, removal of 3 of the 4 normal glands

A

Causes transient hypoparathyroidism

100
Q

If the parathyroid glands were accidentally removed during surgery, the person would suffer from

A

Tetany, a severe convulsive disorder

101
Q

The parathyroid glands are ovoid bodies measuring about

A

6mm long in their greatest diameter
3mm wide
2mm thick
Approx. 40mg

102
Q

Serve mainly to support the parenchyma consisting of cords or clusters of epithelial cells surrounded by reticular fibers

103
Q

Major fxnal parenchymal cells of parathyroid glands are the slightly eosinophilic-staining

A

Chief cells

104
Q

is synthesized in ribosomes of the RER to form proparathyroid hormones and a polypeptide

A

Preproparathyroid hormone

105
Q

Probably present inactive phases of single cell type with chief cells being the actively secreting phase

A

Intermediate cells

106
Q

Usually supply arterial blood to the parathyroid glands but they may be supplied by the superior thyroid arteries, thyroidea ima, esophageal arteries

A

Inferior thyroid arteries

107
Q

Parathyroid veins drain into the plexus of veins on the

A

Anterior surface of the thyroid gland and trachea

108
Q

Nerves of the parathyroid glands are derived from the thyroid branches of the

A

Cervical sympathetic ganglia

109
Q

Polypeptide chain of 115 AA

A

Preprohormone

110
Q

With 90AA

A

Prohormone

111
Q

The final hormone has a molecular weight of about

112
Q

The normal plasma lvl of intact PTH of

A

10-55pg/mL

113
Q

PTH half-life

A

10 minutes

114
Q

Doesn’t bind bind PTHrP and found in the brain, placenta and pancreas

A

Second receptor, PTH2 (hPTH2-R)

115
Q

Reacts w the carboxyl terminal rather than the amino terminal of PTH.

A

Third receptor

CPTH

116
Q

The first 2 are serpentine receptors coupled to Gs and via this heterotrimetric G protein they activate

A

Adenylyl cyclaee

- increasing intracellular cAMP

117
Q

In the parathyroid, its activation

A

Inhibits PTH secretion

118
Q

Acts directly on the parathyroid glands to decrease preproPTH mRNA

A

1,25-dihydroxycholecalciferol

119
Q

Stimulates PTH secretion by lowering plasma Ca and inhibiting the formation of 1,25-dihydroxycholecalciferol

A

Increased plasma phosphate

120
Q

Required to maintain normal parathyroid secretory responses

Impaired PTH release along with diminished target organ responses to PTH account for the hypocalcemia that occasionally occurs in Mg deficiency

121
Q

PTH action on bone is increased mobilization of Ca and Phos (i.e bone dissolution) from the

A

Nonreadily exchangeable Ca pool

122
Q

The long term effects of PTH on bone remodeling, wc involves

A

Bone resorption and accretion

123
Q

Stimulate bone syn

124
Q

In adults, hematopoietic tissue is more abundant in

A

Trabecular bone

125
Q

A mediator of bone resorption bcs PTH stimulates adenylyl cyclase in bone cells

126
Q

With the dissolution of stable bone, _____ is excreted in the urine. This forms tye basis for assessing collagen metabolism and thereby the relative rate of bone resorption

A

Hydroxyproline

127
Q

Both active and passive transport but most of the intestinal absorption of Ca occurs via facilitated diffusion

A

Ca and Phos absorbed by intestine

128
Q

They act synergistically to absorb Ca and Phos

A

PTH and calcitriol

129
Q

Increased intestinal absorption of Ca promoted by PTH is mediated indirectly through the increased synthesis of

Acts on the intestine to promote the transport of Ca and Phos

A

Calcitriol

130
Q

Increased intestinal absorption of Ca promoted by PTH is mediated indirectly through the increased synthesis of

Acts on the intestine to promote the transport of Ca and Phos

A

Calcitriol

131
Q

PTH increases the renal threshold for Ca by

A

Promoting the active reabsorption of Ca by the distal nephron, including the distal tubule, cortical thick ascending limb of LoH, and connecting segment

132
Q

PTH inhibits

A

The proximal tubular reabsorption of Ca

133
Q

PTH inhibits

A

Phosphate reabsorption in the proximal tubules (lowers renal threshold for HPO4 wc leads to a phosphatase diuresis (phosphaturia))

134
Q

Both increased PTH secretion and Phosphate depletion stimulate the formation of

A

Calcitriol via the activation of 1a-hydroxylase

135
Q

The phosphaturic effect of PTH may be mediated by

A

cAMP, bcs PTH activates adenylyl cyclase in the renal cortex

136
Q

PTH increases the urinary excretion of

A

Na, K and HCO3

137
Q

PTH decreases the excretion of

138
Q

The unopposed effects of PTH on bone, intestines and kidney include

A

Hypercalcemia
Hypophosphatemia

Hypocalciuria
Hyperphosphaturia

139
Q

32 AA polypeptide w an AT disulfide bridge linking positions 1 and 7 and an amidated carboxy terminus

MW 3400

A

Calcitonin

140
Q

Syn in C cells or parafollicular cells of neuroendocrine origin

Loc: within thyroid gland but to a lesser extent the thymus gland

A

Calcitonin

141
Q

Calcitonin half-life

142
Q

Serpentine receptors for calcitonin are in

A

Bones

Kidneys

143
Q

Lowers the circulating Ca and Phosphate lvls

A

Calcitonin

144
Q

Calcitonin exerts its calcium lowering effect by

A

Inhibiting bone resorption

145
Q

This action is direct abd calcitonin inhibits the activity of

A

Osteoclasts in vitro

146
Q

Calcitonin increases Ca excretion in

147
Q

Serves as the second messenger for calcitonin action

148
Q

Synthesis and secretion qof calcitonin are ctrlled by the

A

conc of ionized serum Ca

149
Q

Increase Ca 9mg/dL

A

Calcitonin secretion increases in a linear fashion

150
Q

Decreased ionized Ca = increase PTH secretion to restore serum Ca =

A

Decrease calcitonin to remove a hypocalcemic effect

151
Q

Inhibits osteoclastic activity

Antihypercalcemic effect is c/b principally by the direct inhibition of bone resorption

A

Calcitonin

152
Q

Associated w an increase in alkaline phosphatase synthesis from the osteoclasts

Promotes urinary excretion of Ca , phosphate and Na

Inhibits renal 1a-hydroxylase activity

A

Calcitonin

153
Q

Effects of calcitonin are most marked when the rates of bone turnover and osteoclast fxn are highest, as in the young or in dses such as

A

Paget’s dse

154
Q

In the epidermis, the previtamin 7-dehydrocholesterol is transformed into the

A

Lipid-soluble vitamin D3

155
Q

Teh plant sterol is transformed into Vit D2 (ergocalciferol) by irradiation and has been the main source of vit D that added to food (melk)

A

Ergosterol

156
Q

In the liver, vit D3 is converted to calcidiol is converted to calcitriol by the action of

A

1a-hydroxylase

157
Q

The reaction involves the rapid formation of previtamin D3 wc is converted more slowly to

A

vit D3 (cholecalciferol)

158
Q

Normal plasma lvl if 25 hydroxycholecalciferol

159
Q

Normal 1-25dihydroxycholecalciferol

A

0.03ng/mL (approx. 100 pmol/L)

160
Q

They are steroids in wc one of the rings has been opened

A

VitD2 and its derivatives are secosteroids

161
Q

Increases the activity of 1a-hydroxylase and circulating 1,25-dihydroxycholecalciferol is increased during lactation

162
Q

Increases total circulating 1,25-dihyroxycholecalciferol but this is probably dt a increase in the secretion of its binding protein w/o any steady state change in free, 1,25-dihydroxycholecalciferol

163
Q

Associated w decreased circulating 1,25-dihydroxycholecalciferol and an increase incidence of osteoporosis

A

Hyperparathyroidism

164
Q

Stimulate 1,25-dihy formation

A

GH, hCS and Calcitonin

165
Q

Depresses prodxn of 1,25-dihy

A

Metabolic acidosis

166
Q

The mRNAs that are produced in response to 1,25-dihy dictate the formation of a family of

Also members of trop C

A

Calbindin-D proteins

167
Q

MW of 9000 and binds 2 Ca

A

Calbindin-D 9K

168
Q

MW of 28,000 and binds 4 Ca even though it has 6 Ca binding sites

A

Calbindin-D 28K

169
Q

Increase Ca absorption

Facilitates Ca reabsorption in the kidneys

170
Q

Acts on bone, where it mobilizes Ca and PO4^3- by increasing the number of mature osteoclasts

Stimulates osteoblasts but net effect is still Ca mobilization

171
Q

Promotes the distal tubular reabsorption of Ca

A

Calcitriol

172
Q

Direct effect of calciferols on bone is

A

Resorption

173
Q

Plays imp role in both bone absorption and bone deposition

174
Q

Signs of neuromuscular hyperexcitability appear
Full blown hypocalcemic tetany

Plasma phosphate lvls usually rise as the plasma Ca lvl fall after parathyroidectomy but rise doesn’t always occur

A

Hypoparathyroidism

175
Q

A quick contraction of the ipsilateral facial muscles elicited by tapping over facial nerve at angle of jaw

A

Chvostek’s sign

176
Q

Spasm of the muscles of the upper ex that causes flexion of the wrist and thumb w extension of the fingers

A

Trousseau’s sign

177
Q

When the parathyroid gland are suddenly removed, the Ca lvl in bld falls from the normal 9.4mg/dL to

A

6-7mg/dL within 2-3 days and bld phosphate conc may double

178
Q

Failure to absorb fat

A

Steatorrhea

179
Q

Resulting from congenitally reduced absorption of phosphates by the renal tubules

A

Congenital hypophosphatemia

180
Q

Inappropriate, excess PTH secretion

A

Primary hyperparathyroidism

181
Q

Causes extreme osteoclastic activity in the bones
This elevates the Ca ion conc in the ECF while usually depressing the conc of phosphate ions bcs of increased renal excretion of phosphate

A

Hyperparathyroidism

182
Q

The cystic bone dse of hyperparathyroidism

A

Osteitis fibrosa cystica

183
Q

Important diagnostic findings in hyperparathyroidism

A

High lvl plasma alkaline phosphatase

184
Q

Cause the plasma Ca lvl to rise to

A

12-15mg/dL

185
Q

High lvls PTH as compensation for hypocalcemia rather than as primary abnormality

A

Secondary hyperparathyroidism

186
Q

C/b vit D def or chronic renal dse

A

Sec hyperparathyroidism

187
Q

Hypercalcemia by eroding bone

A

Local osteolytic hypercalcemia

188
Q

Elevated circulating lvls of PTHrP

A

Humoral hypercalcemia of malignancy

189
Q

A condition in wc there’s a chronic moderate elevation in plasma Ca bcs the feedback inhibition of PTH secretion by Ca is reduced

A

Familial benign hypocalciuric hypercalcemia

190
Q

Indivs who r homozygous for inactivating mutations develop

A

Neonatal severe primary hyperparathyroidism

191
Q

Indivs w activating mutations of the gene for the Ca receptor develop

A

Familial hypercalciuric hypocalcemia d/t increased sensitivity of parathyroid glands to plasma Ca

192
Q

S&S hypercalcemic dse

A 
Fatigue, lethargic, weak
Confusion, coma
Anorexia, nausea
Abdominal pain, constipation
Polyuria, polydipsia, nocturia
Widespread soft tissue calcification
193
Q

S&S hypocalcemia

A 
Perioral parasthesias, tingling of fingers and toes
Spontaneous tetany
Chvostek's (+)
Trousseau's (+)
Rickets
194
Q

Labs of hypercalcemic

A 
Serum Ca >3mmol/L (12mg/dL)
Cardiac arrhythmia (bradyarrhythmias or heart block)
195
Q

Labs for hypocalcemic dse

A

Dec serum Ca of 0.2 mmol/L for every 10g/L decrease in albumin
Prolonged QT int and marked ST and QRS changes that mimic an MI

ENDOCRINE SYSTEM (6 decks)

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