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Endo/Repro > Calcium and Phosphate > Flashcards

Calcium and Phosphate Flashcards

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1
Q

Does Hypocalcelmia increase or decrease NM excitibility?

A

Increase (hypocalcemic tetany/spasticity)

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2
Q

Does Hypercalcemia increase or decrease NM excitibility?

A

Decrease

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3
Q

Regulators of Calcium in plasma

A

PTH
Calcitriol
Calcitonin

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4
Q

What clinical conditions cause elevation of serum Calcium?

A

Primary Hyperparathyroidism

Malignancy

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5
Q

What clinical conditions cause low serum Calcium?

A

Hypoparathyroidism
Renal disease
Vitamin D deficiency

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6
Q

What are the three organ systems regulating calcium homeostasis?

A

Bone
Kidney
Intestines

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7
Q

Extracellular concentration of Pi is inversely or directly correlated to that of Ca2+?

A

Inversely

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8
Q

What are the 4 classic regulators of phosphate metabolism?

A

Dietary phosphate intake
Calcitriol
PTH
Renal tubular reabsorption

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9
Q

Calcitriol increases or decreases

Pi resorption from bone?

Pi Absorption from intestine?

Pi reabsorption from kidney?

A

Increases
Increases
Increases

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10
Q

Which hormone directly increases Pi resorption from bone and indirectly increases intestinal absorption through stimulation of calcitriol?

A

PTH

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11
Q

Renal tubular reabsorption of phosphorus is stimulated by ________ ________ _____ and inhibited by ____ .

A

Tubular filtered load; PTH

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12
Q

Gain of function mutations in FGF-23 causes _________ .

A

Achondroplesia

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13
Q

Three renal effects of FGF-23

A
  1. Directly downregulate the NaPi transporters in kidney
  2. Indirectly downregulates NaPi transporters in kidney by stimulating PTH
  3. Decreases calcitriol production in the kidney
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14
Q

Where is FGF-23 derived from?

A

Bone

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15
Q

Other hormones increasing Pi renal reabsorption

A

GH
Insulin
TH

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16
Q

Other hormones decreasing Pi renal reabsorption

A

Calcitonin
Glucocorticoids
ANP
PTH

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17
Q

Impairment of FGF-23 secretion leads to ___________ .

A

Hyperphosphatemia

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18
Q

What cells in parathyroid gland synthesize and secrete PTH?

A

Chief cells

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19
Q

Biologically active PHT is a single-chain polypeptide consisting of how many AAs?

A

84

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20
Q

Low or high plasma levels of Ca2+ stimulate PHT secretion?

A

Low

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21
Q

How does low plasma Ca2+ stimulate PHT secretion?

A

In low Ca2+ conditions, Ca sensing receptor (CaSR) is not stimulated.

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22
Q

What activates CaSR?

A

High Ca2+ levels

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23
Q

What does CaSR do when stimulated?

A

Inhibits transcription of PTH

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24
Q

What is the result of mutation in CaSR?

A

Familial hypocalciuric hypercalcemia (FHH)

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25
PTH signals through ____.
GPCR (s and q)
26
PTH in bone
Increase Ca2+ resorption Increase Pi resorption Increase blood Ca and Pi levels
27
PTH in kindney
Increase Ca2+ reabsorption Decrease Pi reabsorption Increase urinary cAMP
28
PTH in intestine
Increase Ca+ absorption by stimulating calcitriol synthesis
29
Vit D increases calcium and phosphate products to promote ___________ of new bone.
mineralization
30
Active form of Vit D
1,25 (OH)2D3
31
Inactive form of Vit D3
24,25 (OH)2D3
32
Main circulating form of VitD
25-OH-Cholecalciferol
33
Which enzyme makes the final active 1,25-(OH)2-cholecalciferol?
1-alpha-hydroxylase (aka CYP1alpha)
34
What stimulates 1-alpha-hydroxylase?
Decreased [Ca2+] Decreased [Pi] Increased PTH
35
Where is 1-alpha-hydroxylase secreted?
Kidney
36
Where are PTH receptors located in bone?
On osteoblasts
37
Short-term actions of PTH on bone
Enhances bone formation by directly acting on osteoblasts
38
Long-term actions of PTH on bone
Bone resorption (indirectly acts on osteoclasts)
39
Action of Vitamin D on bone
Acts synergistically with PTH to stimulate osteoclast activity and bone resorption
40
Agents involved in bone formation and resorption
M-CSF RANKL RANK OPG
41
Role of M-CSF
Macrophage colony stimulating factor that induces stem cells to differentiate into mature osteoclasts
42
Which cells in the bone produce RANKL?
Osteoblasts
43
What is the role of RANKL?
Mediator for osteoclast formation
44
What is RANK and where is it located?
Cell surface protein located on osteoclasts
45
What produces OPG (Osteoprotegrin)?
Osteoblasts
46
What does OPG do?
It is a "fake" RANKL receptor that binds to RANK and inhibits RANKL/RANK interaction thus inhibiting osteoclast stimulation and bone resorption (bone preserving protein)
47
How does VitD increase absorption of Calcium from intestine?
1. Induces synthesis of calbindin-9k which binds to intracellular calcium and buffers it 2. Induces Ca2+--ATPase that exports Ca2+ across the basolateral membrane
48
Where is Calcitonin produced?
Thyroid gland, C cells
49
Actions of calcitonin on bone
Inhibits bone resorption and decreases Ca and Pi levels in blood Decreases activity of osteoclasts
50
C cells express which receptor that senses high extracellular Ca+ and stimulates calcitonin secretion?
CaSR
51
Conditions causing primary hyperparathyroidism
Adenoma Hyperplasia Cancer
52
Primary hyperthyroidism results in
``` Hypercalcemia Hypophosphatemia Increased bone demineralization Increased GI absorption of Ca2+ (via VitD) Increased Ca2+ reabsorption from kidney ```
53
What is "stones, bones and groans" that is associated with primary hyperparathyroidism?
Stones=Ca2+ oxalate stones in urine=hypercalciuria Bones=Increased bone resorption Groans=constipation
54
What is the main cause of secondary hyperthyroidism?
Low blood Calcium levels caused by renal failure or VItD deficiency
55
Possible causes of hypoparathyroidism
Thyroid surgery Parathyroid surgery Autoimmune or congenital disease
56
What is the main result of hypoparathyroidism?
Low calcium
57
What are the main symptoms of hypoparathyroidism?
Tetany, convulsions, paresthesias Muscle cramps Increased NM excitability Poor tooth development (in children)
58
What is Pseudohypoparathyroidism type Ia (aka Albright hereditary osteodystrophy)
Inherited autosomal dominant disorder PTH receptor insensitivity Defective cAMP-mediated signal of PTH (GsAlpha activity diminished) Increased PTH secretion LOW calcium levels
59
Main findings in AHO
Hypocalcemia | Hyperphosphatemia
60
Will administration of exogenous PTH enhance phosphate diuresis, increase in serum calcium, and an increase in urinary cAMP?
Nope
61
Phenotype of AHO?
``` short stature short neck obesity subcutaneous calcification shortened metatarsals and metacarpals ```
62
Humoral hypercalcemic syndrome is associated with ________ .
malignancy
63
What is the peptide produced by tumors in humoral hypercalcemia of malignancy?
PTH-related peptide (PTHrP)
64
PTHrP binds and activates the same receptor as ____ .
PTH
65
How is humoral hypercalcemia of malignancy similar to primary hyperparathyroidism?
Hypercalcemia Hypophosphatemia Increase urinary Pi and cAMP
66
How does humoral hypercalcemia of malignancy differ from primary hyperparathyroidism?
decreased bone formation decreased PTH levels decreased VitD
67
Is PTHrP controlled by circulating Ca levels and does it play a role in Ca/Pi homeostasis?
No
68
What are the characteristics of Rickets?
Insufficient amounts of Ca2+ and Pi available to mineralize growing bone Growth failure and skeletal deformities
69
How many types of Rickets are there?
Two: type I and II
70
Cause of Pseudovitamin D-deficient rickets or vitamin D dependent rickets type I?
Deficient 1-alpha-hydroxylase
71
Cause of Pseudovitamin D-deficient rickets or vitamin D dependent rickets type II?
Deficient VDR
72
What is osteomalacia?
Vitamin D deficiency in adults New bone fails to mineralize Bending and softening of weight-bearing bones
73
Calcitonin effect in kidney
Increases Ca2+ and Pi excretion (inhibits reabsorption)

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