Hormones In Calcium And Bone Metabolism Flashcards
1
Q
A normal adult body contains about
A
1kg of Ca
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)
3
Q
A normal diet provides how much Ca per day
A
20-2000mg with an ave of 1000mg Ca per day
4
Q
Approx. How much is absorbed, in majority in ileum bcs of its large absorptive surface
A
300g
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
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
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
8
Q
The skeleton also serves as a storage depot for phosphorus and contains about how much of the total body phosphorus?
A
80%
9
Q
The plasma conc of total Ca (ionized and non) is about
A
10mg/dL
Equivalent to 5mEq/L or 2.5mmol/L
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%)
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%)
12
Q
Regulates the serum-ionized Ca conc
A
PTH, Calcitonin, Vit D
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
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
15
Q
Total plasma Ca
A
2.50mmol/L
16
Q
This represents the Ca pool that is not readily exchangeable and it is not available for rapid mobilization
A
Larger Ca pool
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
18
Q
When the pH of ECF becomes more acidic, there is a
A
Relative increase in H2PO4 and decrease in HPO4-
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
20
Q
Total body phosphorus is
A
500-800g (16.1-25.8 mol), 85-90% of wc is in the skeleton
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-
22
Q
When Ca intake is high, 1,25-dihydroxycholecalciferol levels fall bcs of
A
Increased plasma Ca
23
Q
Relationship of Ca absorption and Ca intake
A
Inverse
24
Q
Increase absorption
A
Increase CHON diet in adults
25
Ca absorption is also decreased by subs that form
Insoluble salts w Ca (e.g phosphates and oxalates or by alkalis)
26
Enters the intestines via secreted GI juices and sloughed mucosal cells
An additional 250mg/day of Ca
27
How much of daily intake of Ca is excreted in the feces
90% (900mg/day)
28
Pi is absorbed in the duodenum and small intestine by
Active transport and passive diffusion
29
It is linearly proportionate to dietary intake
Absorption of Pi
30
Ingested Ca excreted in urine
10% or 100mg/day
31
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
41%
32
Amount of phosphorus normally entering bone is about
3mg (97 umol/kg/d), w an equal amt leaving via reabsorption
33
% if filtered Pi us reabsorbed
85-90%
34
Proximal tubule accounts for most of the reabsorption, and is inhibited by PTH
Active transport
35
Renal phosphate excretion is ctrlled by an overflow mechanism this is when
Phosphate conc in plasma is below the critical value of abt 1mmol/L
36
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
Above critical conc
37
Ca doesn't require an active transport process bcs the conc gradient across the membrane is
larger for Ca than for any other ion
38
Ca conc in ICF is
10-70 mmol/L
39
Ca in ECF is
10^-3 mol/L (actual value is 2.5x10^-3 mol/L)
40
The Ca gradient from outside to inside the cell is on the order of
10,000 to 1
41
Ca is bound to cell surfaces and has a role in
Stabilization of membrane and intracellular adhesion
42
Chronic hypocalcemia or hypophosphatemia greatly decreases
Bone mineralization
43
Causes NS excitement and tetany
| - increase neuronal mem permeability to Na, easy action potentials
Hypocalcemia
44
At plasma Ca conc about 50% below normal, the peripheral nerve fibers become so excitable that they begin to
Discharge spontaneously
Elicit tetanic muscle contraction
45
Tetany in hand
| Occurs before tetany in other body parts develop
Carpopedal spasm
46
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
Tetany
47
When lvl of Ca in body fluids rises above normal, the ND depress and reflex are sluggish
Decrease QT interval
Lack appetite
Constipation
Depressed contractility of muscle walls of GI
48
Depressive effects begin to appear when the blood Ca rises above
12mg/dL
Marked: 15mg/dL
49
Ca rises above ___ in bld, Ca phos crystals ppt
17mg/dL
50
Exchangeable Ca salts in bones are
Amorphous Ca phos compounds
| - mainly CaHPO4
51
The quantity of these salts that is available for exchange is abt 0.5 to 1% of the tCa salts of the bone
Total of 5-10g Ca
52
Within 3-5 mins after an cute increase in Ca ion conc, the rate of PTH secretion
Decreases
53
Relationship of PTH and Calcitonin
Inverse
54
Causes rapid deposition of Ca in bones
Inc in Calcitonin
55
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
Excess Ca
56
Ca regulation involves 3 tissues, 3 hormones and 3 cell types
3 tissues: bone, intestine, kidney
3 hormones: PTH, calcitonin, activated vit D3
3 cell types: osteoblasts, osteocytes, osteoclasts
57
When plasma Ca falls
PTH secretion increases
58
Hypercalcemic hormone
PTH
59
Hypocalcemic hormone
Calcitonin
60
A 32 AA residue polypeptide secreted by the parafollicular (C) cells of thyroid gland
Calcitonin
61
As plasma Ca increases
Calcitonin secretion increases
62
Calcitonin release is stimulated by
Pentagastrin
63
A secosteroid containing 27 C atoms wc makes it the largest steroid hormone
Vit D3 (cholecalciferol)
64
The major bld form of vit D
Prevent rickets
Calcidiol (25-hydroxyvitamin D3) 25-hydroxycholecalciferol
65
Another active metabolite of vit D
On a molar basis, it is 100x more potent than calcidiol
Calcitriol (1,25-dihydroxyvitamin D3) 25-dihydroxycholecalciferol
66
Inhibits bone resorption and increases the amount of Ca in urine
Calcitonin
67
Acts on one of the PTH receptors and is important in skeletal dev in the uterus
PTHrP
68
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
Glucocorticoids
69
They decrease bone formation by
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
70
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
GH
71
generated by the action of GH stimulates CHON synthesis in the bone
IGF-I
72
may cause hypercalcemia, hypercalciuria and sometimes osteoporosis
Thyroid hormone
73
prevents osteoporosis probably by direct effect on the osteoblasts
estrogen
74
increases bone formation and there is significant bone loss in untreated diabetes
Insulin
75
is found in the form of hydroxyapatite crystals
Bone Ca
76
The empirical chemical formula for this substance is Ca10(PO4)6(OH)2 or {(ICa3PO4)2}3
Hydroxyapatite crystals
77
Fluoride ion can replace the OH- group and form
fluoroapatite {(Ca3PO4)2}3 CaF2
78
Ca:Phos ratio in bone is
1.7:1
79
A large SA is provided by the microcrystalline structure of bone; it is estimated to be
100 acres in human
80
over 90% of organic matrix is
collagen
81
bone is composed of tough organic matrix that is grealy strengthened by
deposits of Ca salts
82
early dev, bone exists as
osteoid - an organic, unmineralized matrix surrounding the bone cells that deposited it
83
embryonic germ layer that gives rise to cartilage, bone and muscle
Mesoderm
84
can differentiate as bone cells including:
1. cells that deposit dentin in teeth
2. cartilage and bone of the head
Neural crest cells
85
are highly differentiated cells that nonmitotic in their differentiated state
osteoblasts
- secrete and synthesize collagen
- cont abundant alk phos
- derived fr BM mesenchyme
86
become buried in bone matrix
has osteolytic activity
no longer syn collagen
osteocytes
87
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
osteoclasts
88
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
Osteoclasts
89
Stimulate osteoblasts
```
PTH
1,25-dihydroxycholecalciferol
IL-1
T3, T4
HGH, IGF-1
PGE2
TNF
Estrogen
```
90
Inhibit osteoblasts
Corticosteroids
91
Stimulate osteoclasts
PTH
1,25-dihyxycholecalciferol
IL-6, IL-11
92
Inhibit osteoclasts
```
Calcitonin
Estrogen (by inhibiting production of certain cytokines)
TGF-B
IFN-a
PGE2
```
93
Arise from the fourth brachial/pharyngeal pouch in conjunction w the ultimobrachial bodies
Superior parathyroid glands
94
Arise from the third brachial/pharyngeal pouches in conjunction w the thymus
Inferior parathyroid glands
95
Are more constant in position and lie at the level of the middle of the posterior border of the thyroid gland
Superior parathyroid glands
96
Close proximity to the cricothyroid membrane, entrance of the recurrent laryngeal nerve and usually cephalad to the
Superior thyroid glands
97
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
Two inferior parathyroid glands
98
Removal of half the parathyroid glands usually causes
No major physiologic abnormalities
99
However, removal of 3 of the 4 normal glands
Causes transient hypoparathyroidism
100
If the parathyroid glands were accidentally removed during surgery, the person would suffer from
Tetany, a severe convulsive disorder
101
The parathyroid glands are ovoid bodies measuring about
6mm long in their greatest diameter
3mm wide
2mm thick
Approx. 40mg
102
Serve mainly to support the parenchyma consisting of cords or clusters of epithelial cells surrounded by reticular fibers
Septa
103
Major fxnal parenchymal cells of parathyroid glands are the slightly eosinophilic-staining
Chief cells
104
is synthesized in ribosomes of the RER to form proparathyroid hormones and a polypeptide
Preproparathyroid hormone
105
Probably present inactive phases of single cell type with chief cells being the actively secreting phase
Intermediate cells
106
Usually supply arterial blood to the parathyroid glands but they may be supplied by the superior thyroid arteries, thyroidea ima, esophageal arteries
Inferior thyroid arteries
107
Parathyroid veins drain into the plexus of veins on the
Anterior surface of the thyroid gland and trachea
108
Nerves of the parathyroid glands are derived from the thyroid branches of the
Cervical sympathetic ganglia
109
Polypeptide chain of 115 AA
Preprohormone
110
With 90AA
Prohormone
111
The final hormone has a molecular weight of about
9,500
112
The normal plasma lvl of intact PTH of
10-55pg/mL
113
PTH half-life
10 minutes
114
Doesn't bind bind PTHrP and found in the brain, placenta and pancreas
Second receptor, PTH2 (hPTH2-R)
115
Reacts w the carboxyl terminal rather than the amino terminal of PTH.
Third receptor
| CPTH
116
The first 2 are serpentine receptors coupled to Gs and via this heterotrimetric G protein they activate
Adenylyl cyclaee
| - increasing intracellular cAMP
117
In the parathyroid, its activation
Inhibits PTH secretion
118
Acts directly on the parathyroid glands to decrease preproPTH mRNA
1,25-dihydroxycholecalciferol
119
Stimulates PTH secretion by lowering plasma Ca and inhibiting the formation of 1,25-dihydroxycholecalciferol
Increased plasma phosphate
120
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
Magnesium
121
PTH action on bone is increased mobilization of Ca and Phos (i.e bone dissolution) from the
Nonreadily exchangeable Ca pool
122
The long term effects of PTH on bone remodeling, wc involves
Bone resorption and accretion
123
Stimulate bone syn
PTH
124
In adults, hematopoietic tissue is more abundant in
Trabecular bone
125
A mediator of bone resorption bcs PTH stimulates adenylyl cyclase in bone cells
cAMP
126
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
Hydroxyproline
127
Both active and passive transport but most of the intestinal absorption of Ca occurs via facilitated diffusion
Ca and Phos absorbed by intestine
128
They act synergistically to absorb Ca and Phos
PTH and calcitriol
129
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
Calcitriol
130
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
Calcitriol
131
PTH increases the renal threshold for Ca by
Promoting the active reabsorption of Ca by the distal nephron, including the distal tubule, cortical thick ascending limb of LoH, and connecting segment
132
PTH inhibits
The proximal tubular reabsorption of Ca
133
PTH inhibits
Phosphate reabsorption in the proximal tubules (lowers renal threshold for HPO4 wc leads to a phosphatase diuresis (phosphaturia))
134
Both increased PTH secretion and Phosphate depletion stimulate the formation of
Calcitriol via the activation of 1a-hydroxylase
135
The phosphaturic effect of PTH may be mediated by
cAMP, bcs PTH activates adenylyl cyclase in the renal cortex
136
PTH increases the urinary excretion of
Na, K and HCO3
137
PTH decreases the excretion of
NH4 and H
138
The unopposed effects of PTH on bone, intestines and kidney include
Hypercalcemia
Hypophosphatemia
Hypocalciuria
Hyperphosphaturia
139
32 AA polypeptide w an AT disulfide bridge linking positions 1 and 7 and an amidated carboxy terminus
MW 3400
Calcitonin
140
Syn in C cells or parafollicular cells of neuroendocrine origin
Loc: within thyroid gland but to a lesser extent the thymus gland
Calcitonin
141
Calcitonin half-life
<10
142
Serpentine receptors for calcitonin are in
Bones
| Kidneys
143
Lowers the circulating Ca and Phosphate lvls
Calcitonin
144
Calcitonin exerts its calcium lowering effect by
Inhibiting bone resorption
145
This action is direct abd calcitonin inhibits the activity of
Osteoclasts in vitro
146
Calcitonin increases Ca excretion in
Urine
147
Serves as the second messenger for calcitonin action
cAMP
148
Synthesis and secretion qof calcitonin are ctrlled by the
conc of ionized serum Ca
149
Increase Ca 9mg/dL
Calcitonin secretion increases in a linear fashion
150
Decreased ionized Ca = increase PTH secretion to restore serum Ca =
Decrease calcitonin to remove a hypocalcemic effect
151
Inhibits osteoclastic activity
| Antihypercalcemic effect is c/b principally by the direct inhibition of bone resorption
Calcitonin
152
Associated w an increase in alkaline phosphatase synthesis from the osteoclasts
Promotes urinary excretion of Ca , phosphate and Na
Inhibits renal 1a-hydroxylase activity
Calcitonin
153
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
Paget's dse
154
In the epidermis, the previtamin 7-dehydrocholesterol is transformed into the
Lipid-soluble vitamin D3
155
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)
Ergosterol
156
In the liver, vit D3 is converted to calcidiol is converted to calcitriol by the action of
1a-hydroxylase
157
The reaction involves the rapid formation of previtamin D3 wc is converted more slowly to
vit D3 (cholecalciferol)
158
Normal plasma lvl if 25 hydroxycholecalciferol
30ng/mL
159
Normal 1-25dihydroxycholecalciferol
0.03ng/mL (approx. 100 pmol/L)
160
They are steroids in wc one of the rings has been opened
VitD2 and its derivatives are secosteroids
161
Increases the activity of 1a-hydroxylase and circulating 1,25-dihydroxycholecalciferol is increased during lactation
Prolactin
162
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
Estrogen
163
Associated w decreased circulating 1,25-dihydroxycholecalciferol and an increase incidence of osteoporosis
Hyperparathyroidism
164
Stimulate 1,25-dihy formation
GH, hCS and Calcitonin
165
Depresses prodxn of 1,25-dihy
Metabolic acidosis
166
The mRNAs that are produced in response to 1,25-dihy dictate the formation of a family of
Also members of trop C
Calbindin-D proteins
167
MW of 9000 and binds 2 Ca
Calbindin-D 9K
168
MW of 28,000 and binds 4 Ca even though it has 6 Ca binding sites
Calbindin-D 28K
169
Increase Ca absorption
Facilitates Ca reabsorption in the kidneys
1,25-dihy
170
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
1,25-dihy
171
Promotes the distal tubular reabsorption of Ca
Calcitriol
172
Direct effect of calciferols on bone is
Resorption
173
Plays imp role in both bone absorption and bone deposition
Vit D
174
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
Hypoparathyroidism
175
A quick contraction of the ipsilateral facial muscles elicited by tapping over facial nerve at angle of jaw
Chvostek's sign
176
Spasm of the muscles of the upper ex that causes flexion of the wrist and thumb w extension of the fingers
Trousseau's sign
177
When the parathyroid gland are suddenly removed, the Ca lvl in bld falls from the normal 9.4mg/dL to
6-7mg/dL within 2-3 days and bld phosphate conc may double
178
Failure to absorb fat
Steatorrhea
179
Resulting from congenitally reduced absorption of phosphates by the renal tubules
Congenital hypophosphatemia
180
Inappropriate, excess PTH secretion
Primary hyperparathyroidism
181
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
Hyperparathyroidism
182
The cystic bone dse of hyperparathyroidism
Osteitis fibrosa cystica
183
Important diagnostic findings in hyperparathyroidism
High lvl plasma alkaline phosphatase
184
Cause the plasma Ca lvl to rise to
12-15mg/dL
185
High lvls PTH as compensation for hypocalcemia rather than as primary abnormality
Secondary hyperparathyroidism
186
C/b vit D def or chronic renal dse
Sec hyperparathyroidism
187
Hypercalcemia by eroding bone
Local osteolytic hypercalcemia
188
Elevated circulating lvls of PTHrP
Humoral hypercalcemia of malignancy
189
A condition in wc there's a chronic moderate elevation in plasma Ca bcs the feedback inhibition of PTH secretion by Ca is reduced
Familial benign hypocalciuric hypercalcemia
190
Indivs who r homozygous for inactivating mutations develop
Neonatal severe primary hyperparathyroidism
191
Indivs w activating mutations of the gene for the Ca receptor develop
Familial hypercalciuric hypocalcemia d/t increased sensitivity of parathyroid glands to plasma Ca
192
S&S hypercalcemic dse
```
Fatigue, lethargic, weak
Confusion, coma
Anorexia, nausea
Abdominal pain, constipation
Polyuria, polydipsia, nocturia
Widespread soft tissue calcification
```
193
S&S hypocalcemia
```
Perioral parasthesias, tingling of fingers and toes
Spontaneous tetany
Chvostek's (+)
Trousseau's (+)
Rickets
```
194
Labs of hypercalcemic
```
Serum Ca >3mmol/L (12mg/dL)
Cardiac arrhythmia (bradyarrhythmias or heart block)
```
195
Labs for hypocalcemic dse
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
