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Endo/Repro Exam 1 > Regulation of Calcium and Phosphate Metabolism > Flashcards

Regulation of Calcium and Phosphate Metabolism Flashcards

1
Q
  • _ contains most of the Ca2+ stores in the body
  • _ is the biologically active form of Ca2+
  • of the 60% . of unfilterable Ca2+, 10 % are _ and 50% are
A
  • Bones/Teeth
  • Free, ionized
  • 10% is complexed to anions
  • 50% are free ionized
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2
Q
  • What are symptoms of hypocalcemia?
A
  • Hyperreflexia
  • Spontaneous twitching
  • Muscle cramps
  • Numbness and tingling
  • Tetany
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3
Q
  • What are two indicators of hypocalcemia?
A
  • Chvostek sign: twitching of the facial muscles elicited by tapping on facial nerve
  • Trousseau sign: Carpopedal spasm upon inflation of blood pressure cuff
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4
Q
  • What are symptoms of hypercalcemia?
A
  • Decreased QT interval
  • Constipation
  • Lack of appetite
  • Polyuria
  • Polydipsia
  • Muscle weakness
  • Hyporeflexia
  • Lethargy
  • Coma
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5
Q
  • Hypocalcemia results in _ membrane excitability and is the basis for hypocalcemic tetany
  • Hypercalcemia results in _ membrane excitability
A
  • Hypocalcemia-increased membrane excitability (reduces activation threshold for Na+ channels, easier to evoke AP)
  • Decreased (Nervous system becomes depressed and reflexes are slowed)
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6
Q

Changes in calcium conentration can occur via what 3 primary ways?

A
  • Changes in plasma protein concentration
    • Increase in plasma protein, increase in total Ca2+ concentration and vice versa
    • No change in Ca2+ ionized (protein changes are usually more chronic issues)
  • Changing anion concentration
    • Increase in Pi concentration will decrease Ca2+ ionized concentration
  • Acid-Base Abnormalities
    • Alters ionized concentration by changing the fraction of Ca2+ bound to Albumin
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7
Q
  • Changes in calcium levels during acidemia
  • Changes in calcium levels during alkalemia
A
  • Acidemia
    • Increase in free ionized Ca2+ cuz less is bound to Albumin (H+ is taking Ca2+’s binding spots(
  • Alkalemia
    • Decrease in free ionized Ca2+ because more is bound to Albumin (often is accompanied by hypocalcemia)
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8
Q
  • What three organs are important in maintaining Ca2+ homeostasis?
  • What three hormones are important in maintainin Ca2+ homeostasis?
A
  • Bone, kidney, intestine
  • PTH, Vitamin D, Calcitonin
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9
Q
  • Identify the following hormones in their role in Ca2+ homeostasis
A
  1. Vitamin D
  2. PTH
  3. Vitamin D
  4. Calcitonin
  5. PTH (promotes reabsorption of Ca2+ and excretion of PO43-)
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10
Q
  • What is the relationship between Ca2+ and PO43- concentration in the ECF?
  • Most Pi is distributed in _
  • The 1% that is in the plasma, some is _, some _ bound and some _
A
  • Inversely proportional to one another (high ca2+, low Pi)
  • Both are regulated by the same hormones
  • Most is distributed in bone (85%)
  • Ionized (84%), Protein bound, Complexed to cations
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11
Q
  • PTH is secreted by _ cells in the _ gland
  • _ is the stimuli for secretion
  • Synthesis of PTH
    • Synthesized as a _
    • Eleaved to form _
    • Transported to golgi and cleaved to form _
    • 84 aa’s long with most biologically active portion of the hormone being located towards the _ terminus of the AA
A
  • Chief cells, Parathyroid
  • Decreased serum Ca2+
  • preprohormone
  • prohormone
  • PTH
  • N terminus (AAs 1-34)
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12
Q
  • Regulation of PTH gene expression and secretion
    • ​Increased Ca2+ levels in the blood are sensed by the _ receptor and activate _ and _ downstream signaling pathways to inhibit PTH gene transcription and exocytosis of PTH
    • _ inhibits PTH gene transcription and promotes transcription of _ gene
A
  • CaSR
  • Gq and Gi (note Gq is inhibitory in this case)
  • 1,25 Vitamin D-promotes CaSR gene transcription
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13
Q
  • Chronic hypercalcemia
    • ​_ PTH synthesis and storage, and _ breakdown of stored _ and release of inactive fragments into the bloodstream
  • Chronic hypocalcemia
    • ​_ PTH synthesis and sotrage
    • _ of parathyroid glands (2ndary _)
  • Magnesium
    • ​Parallels PTH secretion
  • Severe Hypomagnesemia (EX: Alcoholism)
    • ​_ of PTH storage, synthesis and secretion
A
  • Decrease, increase breakdown of stored PTH
  • Increase PTH synthesis and storage
  • Hyperplasia (2ndary hypoparathyroidism)
  • Decrease
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14
Q
  • PTH acts on the bone and kidney tubule via which type of receptor?
A
  • GPCR (Gs)
  • Increased cAMP and adenylyl cyclase and PKA
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15
Q
  • Action of PTH in the bone
  • Action of PTH on the kidney
  • Action of PTH on the intestine
A
  • Increase bone resorption
  • Increased reabsorption of Ca2+, Increased excretion of Pi and cAMP in the urine
  • Indirectly increases absorption of Ca2+ from intestine d/t actions of Vitamin D
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16
Q

Function of Vitamin D

Properties of its synthesis

Has a _ receptor with what two receptor components

A
  • Functions
    • Increase Ca2+ and Pi plasma concentrations
    • Increase Ca2+ and Pi product to promote mineralization of new bone
    • Has actions on intestine, kidney, and bone
  • Synthesis
    • Made as a prohormone
    • Hydroxylated at least twice to form an active metabolite
    • Regulated by (-) feedback
    • Has nuclear receptor (with Vitamin D receptor component and Retinoid X component)
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17
Q
  • What enzyme converts 25 OH cholecalciferol to 1,25 dihydroxycholecalciferol and where is this enzyme located?
  • What stimulates this enzyme?
A
  • 1 alpha hydroxylase, proximal tubule of the kidney
  • Low calcium and pi, high PTH
18
Q
  • Renal 1 alpha hydroxylase is also known as _
  • Increased Ca2+ is sensed by the _ to inhibit transcription of the _ gene (acting via which GPCR receptor pathway?)
  • Increased PTH is sensed by GPCR and activates _, increasing the transcription of _ gene
  • 1,25 dihydroxycholecalciferol inhibits transcription of _ gene and stimulates transcription of _ gene to produce 24 hydroxylase (AKA the inactive form of vitamin D)
A
  • CYP1alpha
  • CaSR, CYP1alpha (Gq,Gi)
  • Gs (cAMP/PKA), CYP1alpha
  • CYP1alpha, CYP24
19
Q
  • PTH receptors are located on what cells in the bone?
  • Short term actions of PTH?
  • Long term actions of PTH on bone?
  • Vitamin D actions on bone?
A
  • PTH receptors are located on osteoblasts
  • Short term: PTH promotes bone formation (tx for osteoporosis)
  • Long term: Increase bone resorption (indirectly thru the release of cytokines from osteoblasts acting on osteoclasts)
  • Vitamin DL Stimulates osteoclast activity and bone resorption
20
Q
  • Function of M-CSF
A
  • induces stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts, and mature multinucleated osteoclasts
21
Q
  • Function of RANKL
A
  • Receptor for NF-kB ligand
  • Cell surface protein produced by osteoblasts, bone lining cells, and apoptotic osteocytes
  • Primary mediator of osteoclast formation
22
Q
  • RANK function
A
  • Cell surface protein receptor on osteoclasts and osteoclast precursors
23
Q
  • OPG function
A
  • Produced by osteoblasts
  • Decoy receptor for RANKL:
  • Inhibits RANKL/RANK interaction
24
Q
  • How does PTH work on the agents in bone formation/reabsorption?
  • How does vitamin D work on the agents in bone formation/reabsorption?
A
  • Increase RANKL, Decrease OPG
  • Increase RANKL
25
Q
  • How does PTH work on the kidney?
A
  • PTH binds GPCR on basolateral surface of cell in proximal tubule of kidney
  • Activates Gs and cAMP/PKA
  • PKA phosphorylates Na+/Pi cotransporter on apical surface, preventing Pi reabsorption
  • cAMP is excreted w/ Pi
26
Q
  • How does Vitamin D promote Ca2+ absorption in the intestine?
A
  • Increases transcription of :
    • Ca2+ transporter (TRPV6) on apical membrane
    • Ca2+/3 Na+ exchanger on basolateral membrane
    • Calbindin
27
Q
  • Summary of PTH actions on Ca2+ and Pi homeostasis
A
28
Q
  • Summary of Vitamin D actions on Ca2+ and Pi homeostasis
A
29
Q
  • Actions of calcitonin
A
  • Responds to increase in blood Ca2+
  • Decreases blood Ca2+ and Pi by inhibiting bone resorption (Calcitonin receptors on osteoclasts)
  • Decrease activity and number of osteoclasts
  • No role in chronic regulation of plasma Ca2+
    • Thyroidectomy and thyroid tumors
      • Affect calcitonin levels but have no effect on Ca2+ metabolism
30
Q

_ is a steroid hormone that stimulates intestinal Ca2+ absorption and renal tubular Ca2+ absorption

_ promotes survival of osteoblasts and apoptosis of osteoclasts-favoring bone formation over resorption

_ is a steroid hormone that promotes bone resorption and renal Ca2+ wasting and inhbits Ca2+ absorption in the SI

A
  • Estradiol 17 beta
  • Estrogen
  • Adrenal glucocorticoids
31
Q
  • Primary hyperparathyroidism
    • ​PTH levels
    • Ca2+ levels
    • Pi levels
    • Vitamin D levels
A
  • PTH levels increase
  • Ca2+ levels increase
  • Pi levels decrease
  • Vitamin D levels increase

Sx: Stones, Bones, and Groans

Hypercalciuria-stones

Increased bone resorption-bones

Constipation-groans

Tx: Parathyroidectomy

32
Q
  • Secondary hyperparathyroidism
  • PTH levels
  • Ca2+ levels
  • Pi levels
  • Vitamin D levels
A
  • Increase in PTH levels secondary to low blood Ca2+
  • Low blood Ca2+ causes:
    • Renal failure
    • Vitamin D deficiency
  • Levels
    • PTH increased
    • Low Ca2+
    • Low Pi
    • Low Vitamin D
33
Q
  • Renal failure
    • ​PTH levels
    • Ca2+ levels
    • Pi levels
    • Vitamin D levels
A
  • PTH increased
  • Ca2+ decreased
  • Pi increased
  • Vitamin D decreased
34
Q
  • Hypoparathyroidism
    • Causes
    • Sx
    • Tx
    • Levels of:
      • PTH
      • Ca2+
      • Pi
      • Vitamin D
A
  • Causes
    • Thyroid/parathyroid surfery
    • AID or congenital
  • Sx (associated with hypocalcemia)
    • Muscle spasm or cramping
    • Numbness/tingling or burning around mouth and fingers
    • Seizures
    • In kides, poor tooth development and mental def
  • Tx: Oral Ca2+ supp and active form of Vitamin D
  • Levels
    • Decreased PTH
    • Decreased Ca2+
    • Increased Pi
    • Decreased Vitamin D
35
Q
  • Albright hereditary osteodystrophy (Pseudohypoparathyroidism type 1a)
A
  • AD inherited
  • Gs for PTH in bone and kidney is defective
  • Hypocalcemia nad hyperphosphatemia develop
  • Increase in PTH levels (administation of exogenous PTH doesn’t do anything, no increase in urinary cAMP)
  • Short stature, short neck, obesity, subcutaneous calcification, shortened metatarsals and metacarpals
  • Levels:
    • ​PTH increased
    • Ca2+ decreased
    • Pi increased
    • Vit D decreased
36
Q
  • Humoral hypercalcemia of malignancy
A
  1. PTHrP produced by tumor cells
  2. Binds and activates the same receptor as PTH
  3. Decreased PTH levels
  4. Decreased vitamin D
  5. Increased urinary Ca2+
  6. Increased urinary Pi and cAMP
  7. Increased blood Ca2+
  8. Decreased blood Pi
37
Q
  • Familial hypocalciuric hypecalcemia (FHH):
    • ​PTH levels
    • Serum Ca2+ levels
    • Urine Ca2+ levels
    • Pi levels
    • Vitamin D levels
A
  • AD disorder d/t mutations that inactivate CaSR in parathyroid glands and parallel Ca2+ receptors in ascending limb of the kidney
  • PTH levels are normal or increased
  • Serum Ca2+ elevated
  • Urine Ca2+ low
  • Pi normal
  • Vitamin D normal
38
Q
  • Rickets
A
  • Impaired vitamin D metabolism d/t dietary def or resistance
  • Insufficient Ca2+ and Pi available to mineralize growing bonw
  • Characterized by growth failure and skeletal abnormalities
  • 2 Types:
    • ​Vitamin D Dependent Type I (Pseudovitamin D deficient)-diminished or lowered activity of alpha1hydroxylase
    • Vitamin D Dependent Type II (Pseudovitamin D deficient)-mutations in Vitamin D receptor
  • Levels:
    • PTH: Increased (2ndary)
    • Ca2+: Normal or decreased
    • Pi: Decreased
    • Urine: Increased Pi and cAMP
    • Vitamin D: Decreased
    • Bone: Osteomalacia increases resorption
39
Q
  • Osteomalacia
A
  • New bones fail to mineralize
  • Bending and softening of weight bearing bones
40
Q
  • Tx for osteoporosis
A
  • Anabolic Therapy
    • PTH
  • Antiresorptive therapy
    • Bisphosphates
    • Estrogen
    • Selective estrogen receptor modulators (SERMS: Raloxifene, Tamoxifen)
    • Calcitonin
    • RANKL inhibitors (Denosumab)

Endo/Repro Exam 1 (12 decks)

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