(M) Lec 3: Calcium Homeostasis and Regulation Flashcards
1
Q
- Calcium is the ____ most abundant element by mass
- It is the most abundant ____ by mass in many animals
A
- 5th
- Metal
2
Q
- An adult human body contains ____ grams of calcium
- ____% are hydroxyapatite salts found in bone
- ____% are in the ECF responsible for the biochemical events that take place
A
- 1000g
- 99%
- 1%
3
Q
- The parathyroid gland is the ____ endocrine gland of the body, measuring 6mm (3mm - Bishop) in diameter
- The 2 pairs of gands are located (infront/behind) each lobe of the thyroid gland
- TOF: All individuals have 4 parathyroid glands
A
- Smallest
- Behind
- False
Note: Some people may have 8 glands while some only 2
4
Q
- The parathyroid hormone is composed of how many amino acid residues?
- What are these amino acid fragments called which form the entire sequence?
A
- 84 amino acid residues
- PTH 1-84
5
Q
- This PTH fragment is known as the deficient fragment
- Is the fragment biologically active or inactive?
A
- 7-84 Fragment
- Biologically inactive
6
Q
What does the 7-84 PTH Fragment lack that makes it biologically inactive?
A
Fragments 1 to 11 (it lacks 6 fragments)
Note: Fragment 1 to 11 is the active fragment
7
Q
Cell Types of the Parathyroid
- The secretory cells
- The non-secretory cells
A
- Principal/Chief Cells
- Oxyphil Cells
8
Q
TOF: There is a relationship between the thyroid and parathyroid glands
A
False (they are just placed close together)
9
Q
The parathyroid glands have what kind of receptor that responds to the rising or falling calcium levels by increasing or decreasing PTH secretion?
A
Calcium-Sensing Receptor (CSR)
10
Q
Parathyroid Hormone
- A (hyper/hypo)-calcemic hormone
- Its stimulus is (increased/decreased) levels of blood calcium
- Familiarize yourself with the target organs
A
- Hypercalcemic
- Decreased
- Bones, Kidneys, and Intestines
11
Q
Parathyroid Hormone
- This (prevents/induces) hypocalcemia
- It promotes renal tubular calcium (absorption/resorption) leading to the destruction of bone tissue
- It (increases/decreases) calcium and (increases/decreases) phosphate
A
- Prevents
- Resorption
- Increases; Decreases
12
Q
Parathyroid Hormone
- This stimulates the conversion of Inactive Vitamin D to Active Vitamin D3 which is known as?
- (Enhanced/Reduced) 1ɑ-hydroxylation of 25-hydroxy-vitamin D
- TOF: It indirectly stimulates the intestinal absorption of calcium
A
- Calcitriol
- Enhanced
- True
13
Q
Roles of Calcium
In Membrane Excitation, some of them include calcium channels but calcium entry (requires/doesn’t require) an active transport process because the concentration region across the membrane is (larger/smaller) in calcium than some other ions
A
- Doesn’t require
- Larger
14
Q
Roles of Calcium
Calcium is necessary for the clotting activity of the clotting factors in a process known as what?
A
Hemostasis
15
Q
Roles of Calcium
Muscles (contract/relax) in the presence of calcium ions
A
Contract
16
Q
Roles of Calcium
Calcium is important for the release of hormones by ____ cells and the release of secretory products by ____ cells
A
- Endocrine
- Exocrine
17
Q
Roles of Calcium
True or False:
1. There is calcium efflux during excitatory processes in nerves and muscles
2. Calcium is bound in the cell membrane
3. Calcium plays a role in lactation/milk production
4. It helps in the formation of bones and teeth
5. Helps in the release of neurotransmitters
A
- False (influx)
- True
- True
- True
- True
18
Q
Bone Storage (99%)
- The skeleton of a 70kg person contains about ____ grams of calcium
- It also serves as storage for phosphorus and contains ____% of the total body phosphorus
- The third line of defense in acid-base regulation because of its ____ and ____ component
A
- 100 grams
- 80%
- Bicarbonate and Phosphorus
19
Q
Plasma Storage (1%)
The three forms found in the ECF:
1. 50% (active form)
2. 10% (inactive form)
3. 40% (inactive form)
A
- Ionized or Free
- Complexed with other ions
- Bound to protein (albumin)
20
Q
These 3 hormones are important for the regulation of calcium present in plasma, what are those three?
A
- PTH
- Calcitonin
- Vitamin D
21
Q
Measuring Calcium
This is routinely done as it gives us an idea for measuring all three forms of calcium present in the plasma
A
Total Calcium Determination
22
Q
Measuring Calcium
What is the normal value of Total Calcium Determination? Also give their interpretations if increased and decreased
A
- NV: 10 mg/dL (5 mEq/L or 2.5 mmol/L)
- Increased: Hypercalcemia
- Decreased: Hypocalcemia
23
Q
Calcium Pools refer to the calcium present where?
A
In the bones
24
Q
Calcium Pools
Larger or Smaller Calcium Pools?
- 99% of total body calcium
- The percentage found in stable bones (mature cortical bones)
- The calcium is not readily exchangeable and available for rapid mobilization outside the bone
A
Larger Calcium Pool (Stable Bones)
25
# Calcium Pools
Larger or Smaller Calcium Pools?
- 1% of the total body calcium
- The percentage found in labile bones (young trabecular bones)
- Is readily exchangeable due to physiochemical equilibrium with the ECF
Smaller Calcium Pools (Labile Bones)
26
Smaller calcium pools contain this salt as it provides an immediate reserve for sudden decreases in blood calcium concentration
Calcium-phosphate salt
27
Bones contain (give the percentages):
1. ____% of organic matrix that contains Type 1 Collagen
2. ____% of inorganic material (Ca, P, Mg, Na, and K)
3. ____% water
1. 35%
2. 45%
3. 25%
28
Ca, P, Mg, Na, and K as inorganic materials found in bone form what?
Hydroxyapatite Crystals
29
# Bone Chemistry
1. 70% of bone calcium is in the form of ____
2. The Ca:P ratio is about ____
3. 30% of dry, fat-free bone consists of ____ mineral/inorganic and ____ organic matrix
4. 90% of the organic matrix is made up of ____
1. Hydroxyapatite Crystals
2. 1.7:1
3. 2/3 (mineral/inorganic) and 1/3 (organic)
4. Collagen
30
# Calcium Regulation
The parathyroid gland is not stimulated by hormones produced by the hypothalamus or pituitary gland but instead it is triggered by?
Low calcium levels in the blood
31
TOF: While the parathyroid gland is not stimulated by the hypothalamus and pituitary gland, the three hormones that regulate calcium are (PTH, Calcitonin, and Vit. D3)
False (also not stimulated by them)
32
1. Parathyroid hormones are secreted by the ____ cells of the parathyroid gland
2. It exerts effects on what 3 organs/tissues?
1. Chief/Principal Cells
2. Bones, Kidneys, and Intestines
33
True or False:
1. The PTH only regulates plasma calcium concentrations
2. PTH secretion has a directly proportional relationship to Plasma Calcium levels
1. True
2. False (inverse)
34
1. When plasma calcium levels fall, PTH secretion ____
2. When plasma calcium levels rise, PTH secretion ____
1. Increases
2. Decreases
34
# Biosynthesis of the Parathyroid Hormone
1. PTH is encoded by a gene located on chromosome ____
2. After being translated, it becomes a ____ hormone which contains 115 amino acids
3. In the ER, ____ amino acids are removed
4. After the removal of the amino acids, the hormone is now called as ____ which has 89 amino acids
1. Eleven (11)
2. Preproparathyroid hormone (preproPTH)
3. 29 amino acids
4. Proparathyroid hormone (proPTH)
35
# Biosynthesis of the Parathyroid Hormone
1. In the golgi apparatus, more amino acids are removed by ____ for it to become a mature hormone
2. The mature form now contains ____ amino acid residues
3. It is stored in ____ within the cells and will be released when required
1. Peptidase
2. 84
3. Secretory vesicles
36
- This is secreted by the parafollicular cells (C-cells) of the thyroid gland
- Made up of 32 amino acids
- A hypocalcemic hormone
Calcitonin (CT)
37
Calcitonin levels have a ____ relationship with plasma calcium levels
Linear
38
1. When plasma calcium levels fall, calcitonin secretion ____
2. When plasma calcium levels rise, calcitonin secretion ____
1. Decreases
2. Increases
39
- The largest steroid hormone of the body (its parent cell is cholesterol)
- It contains 27 carbon atoms
Vitamin D3 (Cholecalciferol)
40
As to storage, transport, metabolism, and potency, Vit. D2 and D3 are identical but which is more important for calcium regulation?
Vit. D3
41
# Active Metabolites of Vit. D3
- Aka 25-hydroxyvitamin D3 (25-OH Vit. D3) or 25-hydroxycholecalciferol
- A major blood form of Vit. D
- Is more useful in assessing Vitamin D deficiency or adequacy
Calcidiol
42
# Active Metabolites of Vit. D3
- Aka 1,25-dihydroxyvitamin D3 (1,25-OH2 Vit. D3) or 1,25-dihydroxycholecalciferol
- 100 times more potent than the other metabolite
- The active form of Vitamin D
- Important for calcium regulation or homeostasis in the body
Calcitriol
43
# Synthesis of Active Vitamin D3
Skin, Liver, or Cells of the PCT (Kidneys)?
1. Provitamin 7-dehydrocholesterol is transformed into the lipid-soluble vitamin D3 upon exposure to the sun
2. Calcidiol is converted to calcitriol by the action of 1-alpha-hydroxylase (enhanced by the PTH)
3. Vitamin D3 is converted to Calcidiol by 25-hydroxylase
1. Skin
2. Cells of the PCT
3. Liver
44
Cholecalciferol (vitamin D3) can also come from food intake, also known as?
Ergocalciferol
45
- This comes from plants and is aka plant sterol
- Transformed into a vitamin via irradiation and is the main source of vitamin D (e.g. milk)
Ergocalciferol
46
# Calcium Regulation: Cell Types
- These form the bone matrix
- Highly differential and non-mitotic
- Aka "bone forming" cells derived from the bone mesenchyme
Osteoblasts
47
# Calcium Regulation: Cell Types
1. Osteoblasts synthesize and secrete ____
2. It contains abundant ____ activity
1. Collagen
2. Alkaline Phosphatase
48
# Calcium Regulation: Cell Types
- This maintains bone tissue
- Known as osteoblasts buried in bone matrix
- The most numerous among the bone cells in the mature bone
- Has osteolytic activities and is not capable of synthesizing collagen
- Stimulated by the PTH
Osteocytes
49
# Calcium Regulation: Cell Types
- The rapid movement of calcium ions from bone into the ECF compartment
- It tends to increase the calcium levels in the blood
Osteocytic Osteolysis
50
# Calcium Regulation: Cell Types
Each osteocyte is surrounded by its own lacuna but an extensive canalicular system connects osteocytes and surface osteoblasts forming the ____. Osteocytes and osteoblasts are disrupted at sites where osteoblasts are found.
Functional Syncytium
51
# Calcium Regulation: Cell Types
- This resorbs bone which increases blood calcium levels
- Large, multinucleated cells containing numerous lysosomes and is derived from monocytes
- Is stimulated by the PTH and forms a significant amount of lactic and hyaluronic acid
Osteoclasts
52
# Calcium Regulation: Cell Types
Osteoclast secretions:
1. For the breakdown of bone crystals releasing calcium and phosphate (e.g. lactic and hyaluronic acid)
2. For the digestion of the organic matrix
1. Acid
2. Proteolytic Enzymes
53
# Calcium Regulation: Cell Types
Additional cells:
1. Considered as the stem cell
2. Cells enclosed in the organic matrix of the bone
1. Osteogenic cell
2. Osteoids
54
# Calcium Regulation: Tissues
In osseous tissues:
1. PTH (increases/decreases) the mobilization of calcium and phosphate ions from the non-readily exchangeable calcium pool
2. PTH (inhibits/stimulates) bone synthesis and dissolution
3. PTH has (long/short)-term effects on bones such as bone remodelling
1. Increases
2. Stimulates
3. Long-term
55
# Calcium Regulation: Tissues
True or False (effects of PTH on bones):
1. It stimulates osteoclastic and osteocytic activities
2. It stimulates the fusion of progenitor cells to form multinucleated osteoblastic cells
3. Causes transient enhancement of osteoblastic activity
4. Stimulates the adenyl or adenyl cyclase in bone cells
1. True
2. False (osteoclastic cells)
3. False (transient suppression)
4. True
56
# Calcium Regulation: Tissues
This enzyme stimulated by adenyl or adenyl cyclase is a mediator of bone resorption which can also enhance bone activity
Cyclic Adenosine-3,5-Monophosphate Enzyme
57
# Calcium Regulation: Tissues
In the GIT:
1. Calcium absorption in the intestine occurs via ____
2. ____ is also absorbed in the intestine by both active and passive transport
3. PTH acts synergistically with ____ as it does not directly affect the intestinal absorption of calcium
4. Increased intestinal absorption of Calcium promoted by PTH is mediated (directly/indirectly) through the increased synthesis of calcitriol
1. Facilitated diffusion
2. Phosphate
3. Calcitriol
4. Indirectly
58
# Calcium Regulation: Tissues
Hypoparathyroid or Hyperparathyroid?
1. High activity of PTH = Higher production of Calcitriol = High absorption of Calcium
2. Decreased PTH level = Decreased Calcitriol production = Low Calcium absorption
1. Hyperparathyroid
2. Hypoparathyroid
59
# Calcium Regulation: Tissues
In Renal Tissues:
1. PTH acts to (increase/decrease) the renal threshold for Calcium
2. It promotes active reabsorption of calcium in what 4 parts of the kidney?
3. PTH (promotes/inhibits) phosphate reabsorption in the PCT
1. Increase
2. Distal Nephrons, Cortical Thick Ascending Loop of Henle, Distal Tubules, and Collecting Segments
3. Inhibits
60
# Calcium Regulation: Tissues
If PTH inhibits phosphate reabsorption in the kidneys, it results to a condition which is described as the release of phosphate in the urine, what is this condition called?
Phosphate Diuresis or Phosphaturia
61
# Calcium Regulation: Tissues
Increased PTH secretion and phosphate depletion stimulates the formation of calcium via the activation of this enzyme responsible for converting your calcidiol to calcitriol
1-alpha-hydroxylase
62
# Calcium Regulation: Tissues
During acid-base balance:
1. PTH (increases/decreases) the urinary excretion of sodium, potassium, and bicarbonate
2. PTH (increases/decreases) the excretion of ammonium and hydrogen ions resulting in a metabolic acidosis state
1. Increases
2. Decreases
63
This is located at the cell membranes of each organ (bones, kidneys, and GIT) which mediates the multiple actions of PTH
PTH Receptor
64
This condition refers to decreased calcium secretion in the kidneys because of increased calcium reabsorption
Hypocalciuria
65
In cases of a chronic parathyroid state, though there is an increased level of PTH that will increase serum calcium, the hypercalcemia exceeds the renal threshold which then causes ____
Hypercalciuria
66
PTH increases serum ____ level but decreases serum ____ level. However, in urine, it ____ calcium levels and increases ____ levels.
- Increases serum calcium but decreases serum phospate
- In urine, it decreases calcium levels but increases phosphate levels
67
# Effects of Calcitonin
In Osseous Tissue:
1. It (induces/prevents) bone resorption
2. (Induces/Inhibits) bone osteoclastic and osteocytic bone resorption/activity which promotes the deposition of calcium into the bones
3. (Increases/Decreases) the ALP activity in the bones
1. Prevents
2. Inhibits
3. Increases
68
# Effects of Calcitonin
In the Kidneys: Acute or Long-term?
Increases renal clearance of Na, PO4, and Ca
Acute
69
# Effects of Calcitonin
In the Kidneys: Long-term Effects
1. Inhibits the reabsorption of phosphate in the ____
2. Inhibits the extrusion of ____ from cells
3. Inhibits the renal enzyme, ____
1. PCT
2. Calcium
3. 1-alpha-hydroxylase
70
# Effects of Calcitonin
In the Intestines:
1. (Increases/Decreases) the absorption of Calcium and Phosphates in the jejunum
2. (Inhibits/Promotes) gastric motility and secretion
3. Stimulates intestinal (secretion/reabsorption)
1. Decreases
2. Inhibits
3. Secretion
71
PTH or Calcitonin?
1. Increases serum calcium and decreases serum phosphate
2. Decreases both calcium and phosphate
1. PTH
2. Calcitonin
72
# Effects of Calcitriol
In the bones:
1. (Increases/Decreases) the mobilization of calcium and phosphate from the bones
2. Has a/an (direct/indirect) effect in bone resorption
3. Acts synergistically with ____
1. Increases
2. Direct
3. PTH
73
# Effects of Calcitriol
In the kidneys:
1. Promotes Calcium reabsorption in the ____
2. Promotes Phosphate reabsorption in ____
1. DCT
2. PCT
74
# Effects of Calcitriol
In the intestines:
1. (Increases/Decreases) calcium reabsorption
2. A ____ hormone for the intestinal action of PTH and Calcitonin
3. Lesser (increase/decrease) in intestinal phosphate absorption
1. Increases
2. Mediator
3. Increase
75
# Disorders in Calcium Metabolism
Hyperparathyroidism is related to ____
Hypercalcemia
76
# Disorders in Calcium Metabolism
Hypoparathyroidism, Pseudohypoparathyroidism, and Osteomalacia or Rickets are related to ____
Hypocalcemia
77
# Disorders in Calcium Metabolism
Malabsorption, Vit. D deficiency, renal insufficiency, and renal tubular acidosis are related to what condition under hypocalcemia?
Osteomalacia/Rickets
78
# Disorders in Calcium Metabolism
Hypomagnesemia is related to ____
Hypocalcemia
79
# Disorders in Calcium Metabolism
This hypocalcemia-associated condition:
- Refers to the impairment of calcium reabsorption by the renal tubules
- Presents with decreased excretion of phosphate but with increased values in blood
Acute Pancreatitis
80
# Disorders in Calcium Metabolism
Hypomagnesemia or Hypermagnesemia?
1. Inhibits glandular secretion of PTH, impairs PTH action at its receptor sites, and causes vitamin D resistance
2. May inhibit PTH release and dampen tissue response leading to hypocalcemia and hypercalcinuria
1. Hypomagnesemia
2. Hypermagnesemia
| Note: Both can result in hypocalcemia
81
# Types of Parathyroidism
Increased PTH secretion either due to a problem in the parathyroid gland or a decreased calcium level
Primary Hyperparathyroidism
82
# Types of Parathyroidism
- Increased PTH secretion with the parathyroid gland harboring the problem
- The most common cause of hypercalcemia
- Can be caused by an adenoma/carcinoma or Von-Recklinghausen's disease
Primary Hyperparathyroidism
83
# Types of Parathyroidism
Signs and Symptoms include:
- High serum calcium with low serum phosphates
- Increased urinary calcium and phosphates
- Bone decalcification due to increased osteoclastic activity
- Renal lesions (nephrolithiasis and mephrocalcinosis) and hyperphosphaturia
Primary Hyperparathyroidism
84
# Types of Parathyroidism
- High PTH indicating increased ionized calcium or total calcium
- (+) for hypercalcinuria, hypophosphatemia, and hypercalcemia
Primary Hyperparathyroidism
85
# Types of Parathyroidism
When calcium levels reach ____ mg/dL, the kidneys will not reabsorb the calcium, resulting in hypercalciuria or too much calcium in the urine
12 mg/dL
86
# Types of Parathyroidism
- Due to an underlying cause (not a defect in the parathyroid gland)
- Caused by increased PTH secretion because of hypocalcemia (response to a low level of calcium in the blood)
Secondary Hyperparathyroidism
87
# Types of Parathyroidism
- Related to chronic renal disorders (failure to excrete phosphorus and reabsorb calcium)
- Associated with rickets or osteomalacia
- Can be caused by pregnancies and lactation
- Presents with low serum calcium, high serum phosphates, increased PTH secretion
Secondary Hyperparathyroidism
88
# Types of Parathyroidism
Increased PTH level with decreased ionized calcium (total calcium) but increased phosphorus level
Secondary Hyperparathyroidism
89
# Types of Parathyroidism
- Normal to increased level of phosphate
- There is an underlying cause/disease
Tertiary Hyperparathyroidism
90
# Types of Parathyroidism
- Accidental injury to the parathyroid glands (neck) during surgery
- Infantal, idiopathic, or autoimmune change resulting in decreased activity of the gland leading to hypocalcemia
- There is decreased PTH level with decreased ionized calcium
Hypoparathyroidism
91
# Types of Parathyroidism
- The body fails to respond to PTH due to changes or some mutations that happen in a number of different genes
- The problem is with the response of PTH target tissues
- Calcium is decreased but phosphorus is increased in blood
Pseudohypoparathyroidism
92
# Types of Parathyroidism
- An inherited disorder with no resistance to PTH
- The individual has the phenotypic appearance of pseudohypoparathyroidism but has normal laboratory values
- Genetic defects include: short statures, rounded face, ectopic bones, nuckle-nuckle diple sign, and short metacarpal bones
Pseudopseudohypoparathyroidism
93
# Types of Parathyroidism
Pseudohypoparathyroidism or Pseudopseudohypoparathyroidism?
1. Calcium is decreased but phosphorus is increased
2. All is normal
1. Pseudohypoparathyroidism
2. Pseudopseudohypoparathyroidism
