SM 198a - Calcium and Phosphate Flashcards
(88 cards)
1
Q
FGF-23 will ___________ production of 1,25-OH2 Vitamin D3 (active) by [stimulating/inhibiting] __________________.
A
FGF-23 will decrease production of 1,25-OH2 Vitamin D3 (active) by inhibiting 25 alpha hydroxylase .
FGF-23 is secreted in response to too much serum phosphorous
2
Q
What belongs in box E?
A
1,25-OH2-D3
The active form of vitamin D3
PTH upregulates 1 alpha hydroxylase activity -> more 1,25-OH2-D3 -> works to increase serum Ca2+
FGF23 inhibits 1 alpha hydroxylase activity -> less 1,25-OH2-D3 -> works to decrease serum Ca2+
3
Q
Which enzyme belongs in box B?
Where does it act?
A
25 alpha-hydroxylase
Acts in the liver to covert cholecalciferol to 25-hydroxy-D3
4
Q
What is claudin 16?
What deos it do?
A
Claudin 16 is a protein between the epithelial cells of the thick ascending limb of the loop of Henle
It allows for paracellular reabsorption of Ca2+ down its concentration and electrical gradient
(The lumen in thick ascending loop is positively charged due to the action of ROMK)
5
Q
Which 3 enzymes are important for the synthesis of active vitamin D?
A
- 25 alpha hydroxylase (liver)
- Cholecalciferol -> 25-OH-D3
- 24 alpha hydroxylase (renal PCT cell)
- 25-OH-D3 -> inactive 24,25-OH2-D3
- 25 alpha hydroxylase (renal PCT cell)
- 25-OH-D3 -> active 1,25-OH2-D3
Also: UV light to convert 7-dehydrocholesterol to cholecalciferol
6
Q
What belongs in box A?
A
7-dehydrocholesterol
This is the starting material for active vitamin D synthesis
7
Q
Which enzyme belongs in box C?
A
24 alpha-hydroxelase
Converts 25-OH-D3 to the inactive 24,25-hydroxy-D3
This enzyme is upregulated when serum calcium levels are too high
8
Q
What is the effect of PTH on Ca2+ reabsorption in the intsetine?
A
PTH has no direct effect on Ca2+ reabsorption in the intestine
Vitamin D (1,25 Hydroxy-D3) is the primary regulator of Ca2+ reabsorption in the intestine
However, PTH secreted in response to low Ca2+ increases activation of vitamin D in the kidney, thus indirectly increaseing Ca2+ reabsorption in the intestine
9
Q
When you are re-feeding a patient with starvation, why would you need to give phosphorus as well?
A
Feeding -> increased metabolism -> increased PO4 demand
This uses up the phosphorous that is available in the blood
10
Q
How does FGF-23 affect phosphorous homeostasis?
A
FGF-23 promotes the excretion of phosphorous to lower serum phosphorous levels
11
Q
What factors regulate PTH secretion from the chief cells of the parathryroid gland?
A
- Promote PTH synthesis and release
- Low Ca2+ levels
- Inhibit PTH synthesis and release
- High Ca2+ levels
- High vitamin D
- FGF-23
- Phosphorous
12
Q
What belongs in box B?
A
Cholecalciferol
Created when UV light acts on 7-dehydrocholesterol in the skin
Dietary sources of vitamin D can also enter the vitamin D synthesis pathway here
13
Q
What is the effect of gastric acid on Ca2+ reabsorption?
A
Gastric acid enhances Ca2+ absorption
14
Q
Low PTH is a physiological response to ____________
A
Low PTH is a physiological response to high Ca2+
15
Q
Describe Ca2+ reabsorption in the thick ascending limb of the loop of Henle
A
- K+/Na+/2Cl- cotransporter (NKCC2) in the apical membrane gets these ions from the lumen to the epithelial cell
- Na+/K+ ATPase on the basolateral membrane moves Na+ into the interstitium and K+ into the epithelial cell – electrically neutral
- Chloride channels on the basolateral membrane transport Cl- ions are into the insterstitium
- ROMK on the apical membrane pumps K+ back into the lumen -> positive charge in the lumen
- This positive charge drives paracellular Ca2+ reabsorption through claudin 16
16
Q
Which enzyme belongs in box A?
A
No enzymes!
UV light hits the skin and converts 7-dehydrocholesterol to colecalciferol (pre-vitamin D)
17
Q
Which enzyme blelongs in box D?
A
1-alpha hydroxylase
Converts 25-OH-D3 to the active 1,25-hydroxy-D3
This enzyme is upregulated when serum Ca2+ levels are low
18
Q
Increased bone mineralization will result in [high/low] phosphate in the blood
A
Increased bone mineralization will result in low phosphate in the blood
Bone mineralization moves phosphate from serum -> bone
19
Q
What is the most common cause of hypocalcemia?
A
Low PTH
- Usually post-surgical
- Thyroidectomy, parathyroidectomy, radial neck dissection
- Autoimmune or genetic possible
20
Q
Where in the kidney tubule is the majority of phosphorous reabsorbed?
A
Proximal convluted tubule
21
Q
Describe the clinical manifestation of hyposphosphatemia
A
- Neuro
- Lethergy
- Paraesthesia
- Siezure
- Cardiac
- Arrhythima
- Hypotension
- Hematologic
- Hemolysis
- Skeletal
- Bone demineralization (to increase serum phosphate)
22
Q
What is the active form of vitamin D?
A
1,25 Hydroxy-D3
23
Q
______ is the single most important factor that affects PTH secretion
A
Serum Ca2+ level is the single most important factor that affects PTH secretion
- High Serum Ca2+
- Ca2+ binds to CaSR on the chief cells of the parathyroid gland
- Inhibits PTH production and secretion
- Low Serum Ca2+
- Ca2+ does not bind to CaSR
- PTH is produced and released from the chief cells of the parathyroid gland
24
Q
What stimulus promotes the secretion of FGF-23?
What is the effect?
A
FGF-23 is secreted in response to too much serum phosphorous
FGF-23 -> Decreased Vitamin D synthesis -> decreased phosphorous absorption from the intestine
25
In primary hyperparathyroidism, would you expect the following serum levels to be high or low?
Calcium:
Phosphorous:
1,25-OH2-D3:
* Calcium: **High**
* ****Increased renal reabsorption
* Increased active vitamin D -\> increased intestinal reabsorption
* Increased resorption from bone
* Phosphorous: **Low**
* ****Decreased renal reabsorption
* 1,25-OH2-D3: **Varies**
* Increased vitamin D synthesis in the kidney, but some studies have shown that primary hyperparathyroidism is associated with vitamin D deficiency
26
What is the role of CaSR on Ca2+ reabsorption in the distal convoluted tuble?
In the DCT, CaSR is located on the **apical membrane**
* CaSR senses **increased Ca2+ in the urine**
* If Ca2+ in the urine is high, CaSR stimulates increased reabsorption of PO4 to **prevent kidney stone formation**
27
What factors affect GI absorption of calcium?
* Increase absorption
* **Vitamin D** (1,25-OH2-D3)
* **PTH indirectly,** by increasing Vitamin D syntheisis
* **Gastric acid**
* Decrease abosrption
* **Billiary and pancratic insufficiency**
* Ca2+ binds to unabsorbed fat and is excreted
* **Serum hypercalcemia**
* Via **CaSR**, which binds to Ca2+ and inhibits the effects of vitamin D
28
What is a “pseudo-state” as it refers to an electrolyte?
Low total electrolyte, but no change in the level of its active form
Ex: Low albumin causes a pseudo-decrease in calcium. The amount of protein-bound Ca2+ decreases which decreases total Ca2+, but the levels of ionized (active) Ca2+ remain the same
29
What is the effect of biliary and pancreatic insufficiency on Ca2+ absorption in the gut?
Biliary and pancreatic insufficiency -\> **decreased Ca2+ absorption in the gut**
* Biliary and pancreatic insufficiency -\> **trouble absorbing fat**
* **Ca2+ loves fat**. If there is more fat in the intestine, Ca2+ will bind to it and be excreted.
* Therefore, **Ca2+** **will not be absorbed**
30
How does tumor lysis lead to hypocalcemia?
Would you expect high or low PTH?
* Cell lysis -\> PO4 release
* PO4 in the blod binds to Ca2+, creating a Ca2+/PO4 product
* **This decreases the amount of ionized Ca2+ in the blood**
You would expect **high PTH, since the body is "seeing" low Ca2+ levels due to low ionized Ca2+**
High PTH = physiological response to low Ca2+
31
Which forms of Ca2+ are filtered in the glomerulus?
Ionized Ca2+ only
32
Describe the management of hypercalcemia
* **Improve excretion**
* Saline fluids
* Loop diuretics
* Dialysis (last resort)
* **Decrease production**
* ****Give calcitonin and bisphosphates
* **Treat the underlying cause**
33
What is the effect of PTH on reabsorption of Ca2+ in the kidney?
PTH is secreted when Ca2+ is low, and workds to **increase reabsorption of Ca2+ in the thick ascending limb of the loop of Henle**
* PTH increases Claudin 16 production
* Ca2+ must pass through Claudin 16 in order to be reabsobed paracellularly in the thick ascending limb
34
Describe the process of intestinal absorption of phosphorous
Transcellular transport:
* **NaPi-IIb:** Lumen -\> intestinal cell
Absorbs HPO4- with 2 Na+
* **Unknown channel:** Intestinal cell -\> interstitium
**There is also a paracellular pathway**
35
How does immobilization affect Ca2+ homeostasis?
Immobilization impairs bone formation
* Physical, mechanical load is required to promote bone formation
* Immobilization can result in hypercalcemia
* Less Ca2+ moving into bone = more remains in the serum
36
A 50 year old male with chronic kidney disease stage 5, DM type 2, and hypertension presents for routine follow-up with his nephrologist. Labs reveal markedly elevated serum phosphorous. All of the following interventions would help treat his hyperphosphatemia **except:**
1. Low phosphorous diet
2. Low sodium diet
3. Vitamin D supplementation
4. Dietary phosphorous binders
c. Vitamin D supplementation
37
What substance regulates Calcium absoprtion in the intestine?
**1,25 Hydroxy-D3** (The active form of vitamin D)
* If Ca2+ levels are high, Ca2+ binds to the Ca2+ sensing receptor (CaSR)
* CaSR downregulates 1,25 Hydroxy-D3 synthesis
* Decreased 1,25 Hydroxy-D3 -\> decreased Ca2+ absorption
* If Ca2+ levels are low, CaSR does not downregulate 1,25 Hydroxy-D3 synthesis
* The presence of 1,25 Hydroxy-D3 -\> Ca2+ absorption
38
How do antacids affect Ca2+ absorption?
Gastric acid enhances Ca2+ absorption
Antacids decrease gastric acid, and therefore **decrease Ca2+ absorption**
39
Which form of Ca2+ is biologically active?
Ionized Ca2+
40
What belongs in box D?
**24,25-OH2-D3**
This is a **waste product**, created when the body does not need more active vitamin D3 (ex: when calcium levels are normal or high)
41
What is the effect of CaSR activation on the epithelial cells of the thick ascending loop?
CaSR binds to Ca2+ when serum Ca2+ levels are elevated
Binding of Ca2+ to CaSR **downregulates Ca2+ reabsorption:**
* Decreased ROMK activity
* -\> Decreased liminal positivity
* -\> Decreased driving force for Ca2+ reabsorption
* Decreased Claudin 16 production
* -\> Fewer channels for paracellular Ca2+ reabsorption in the thick ascending limb of the loop of Henle
42
Describe the clinical manifestation of hyperphosphatemia
* Symptoms of **hypocalcemia**
* Phosphorous binds to Ca2+, thus reducing the amount of ionized Ca2+
* Bone fractures, stomach cramps, dysrhythmia, irritability, anxiety, carpopedal spasm, siezure
* Itching
* Metastatic calcifications
43
Describe the management of hypophosphatemia
Eat high-phosphate foods!
* Replete phosphorous
* Eat high-phosphate foods
* IV if severe or patient cannot eat
* Treat underlying cause
44
What are the expected levels for a patient with **hyperparathyroidism?**
Calcium:
Phosphorous:
Calcium: **high**
Phosphorous: **low**
**PTH** = increased renal **Ca2+ reabsorption** and **phosphorous excretion**
45
What is Milk alkali syndrome?
Milk consumption -\> loss of regulation of GI Ca2+ absorption -\> hypercalcemia
46
Describe the process of phosphorous reabsorption in the renal tubules
* **NaPi-IIa and NaPi-IIc:** Lumen -\> Tubular epithelial cell
* **Unknown channel:** Tubular epithelial cell -\> interstitium
47
Which diuretics are known for causing hypercalcemia?
Describe the mechanism
Thiazides
* Decrease Na+ reabsorption in the distal convoluted tubule (Inhibit Na+/Cl- cotransporter)
* -\> Decreased intracellular Na+
* -\> Increased Na+/Ca2+ antiporter activity on the basolateral membrane; **Na+ into the cell, Ca2+ into the interstitium**
* -\> Decreased intracellular Ca2+ **promotes reabosrption of Ca2+ from the lumen via TRPV5**
48
What factors regulate phosphorous reabsorption in the renal tubules?
* **FGF-23**
* ****Acts on FGFR-1 and Klotho to promote the **excretion of phosphorous**
* **PTH**
* ****Promotes the **e****xcretion of phosphorous** by preventing reabsorption
49
What is the effect of vitamin D on PTH in the parathyroid cell?
When Vitamin D reaches a **threshold level in the serum**, it binds to VDR in the chief cell and **inhibits production of PTH**.
-\> decreased GI absorption, renal reabsorption of Vitamin D
50
How would low albumin affect the calcium homeostasis in the blood
Low albumin would decrease the **protein-bound calcium**, thus **lowering total calcium levels** in the body
However, there would be **no change in ionized Ca2+, and therefore no difference in biological funciton**
This means you have to determine low serum Ca2+ levels in the context of albumin
51
What is Calbindin? What does it do?
Calbindin is a protein produced in intestinal epithelial cells
Within the cell, it moves Ca2+ from the luminal side to the serum side
52
FGF-23 plays a very important role in the regulation of vitamin D and PTH.
How?
FGF-23 is the key negative feedback mechanism -
basically FGF-23 is yelling
"CALM DOWN WE HAVE ENOUGH SERUM CA2+"
* **Vitamin D**
* Increases FGF-23 expression in bone
* -\> FGF-23 acts on the kidney to decease vitamin D synthesis
* **PTH**
* Increases FGF-23 express
* -\> FGF-23 acts on teh parathyroid to decrease PTH
53
What factors affect HPO4- absorption in the intestine?
Vitamin D (1,25 Hydroxy-D3) **increases abosrption of HPO4-** in the intestine
54
How does vitamin D affect Ca2+ homeostasis?
Increased levels of active vitamin D (1,25 Hydroxy-D3) **increase Ca2+ absorption in the intestinal epithelium**
* **1,25 Hydroxy-D3** binds to the **Vitamin D Receptor (VDR)**
* **VDR** acts on the nucleus to increase production of **TRPV6, Calbindin, Ca2+ ATPase or Na+/Ca2+**
* All of these proteins are required for Ca2+ reabsorption in the intestine
55
Describe the management of hyperphosphatemia
* Low phosphorous diet (this is hard)
* Give Phosphorous binders
* Bind to and excrete dietary phosphorous
* Common for ESRD and dialysis patients
* Hemodialysis
* Treat underlying cause
56
Why is it important to take Ca2+ supplements with food?
Gastric acid enhances Ca2+ absorption in the gut
Food increases gastric acid secretion, which increases Ca2+ absorption
57
What are the clinical manifestations of hypocalcemia?
* Neuro
* Anxiety, irritability, tetany, twitching, carpopedal spasm, seizure
* Bone
* Fractures
* GI
* Cramps
* Cardiac
* Prolonged QT, dysrhythmia
* Blood
* Hypercoagulable state
58
What is the biggest Ca2+ reservoir in the body?
Bone
59
What is the effect of calcitonin on serum Ca2+?
Calcitonin lowers serum Ca2+
* Increases renal excretion
* Decreases bond resorption
60
What is the effect of estrogen on Ca2+ homeostasis
Estrogen **decreases bond resorption**
It decreases the movement of Ca2+ from bone to serum
61
What is the DDx for hypercalcemia with low PTH?
Low PTH is a normal response to high Ca2+ - the CaSR system is working to suppress PTH secretion
So, what could be causing persistent high Ca2+ in the setting of low PTH?
* If **PTHrP** is elevated, **malignancy is likely**
* If **1,25-OH2-D3** is elevated, **tumor or granulomatous disorder**
* Produces 25 alpha hydroxylase that activates vitamin D
* If **25-OH-D3** is elevated, **vitamin D intake is too high**
* If Vitamin D and PTHrP are normal, consider **myeloma, Vitamin A,** or **thyrotropin**
62
Where in the intestine is Ca2+ absorbed?
Duodenum and jejunum
63
What percentage of filtered Ca2+ is reabsorbed by the kidney tubule?
In which segments of the kidney tubule?
95-99% of filtered Ca2+ is reabsorbed
* **Proximal convoluted tubule:** Most (50-60%) Ca2+ is reabsorbed (Ca2+ follows Na+)
* **Thick ascending limb:** 20-25%
* **Distal convoluted tuble:** 5-10%
* **Collecting tubule = fine tuning**
This is not super different from general reabsorption in the kidney tubules
64
What belongs in box C?
**25-OH-D3**
Created when 25 alpha hydroxylase acts on cholecalciferol in the liver
25-OH-D3 binds to D-binding protein, is exported to the blood and absorbed by a proximal tubular cell (via megalin mediated endocytosis), where it is either **activated to 1,25-OH2-D3** or turned into the **waste product** **24,25-OH2-D3,** depending on the needs of the body
65
What is the most common cause of hyperphosphatemia?
Decreased kidney function resulting in **impaired phosphorous excretion**
Exacerbated by...
* Excess intake
* Cellular breakdown (cells contain a lot of phosphorous)
66
What factors regulate Ca2+ reabsorption in the DCT?
* Vitamin D (1,25 Hydroxy-D3)
* Increases Ca2+ reabsorption
* PTH
* Increases Ca2+ reabsorption
* CaSR on the **luminal** epithelium
* Senses increased Ca2+ in the filtrate
* If Ca2+ is high, CaSR will derease reabsorption of PO4
* This will protect against stone formation
67
How does hypoerphosphatemia lead to hypocalcemia?
Hyperphosphatemia
* -\> Increased FGF-23 + Reduced 1,25-OH2-D3
* Increased FGF-23 further reduces 1,25-OH2-D3 synthesis
* Low active vitamin D -\> **Hypocalcemia**
68
Decreased bone mineralization will result in **_[high/low]_** phosphate in the blood
Decreased bone mineralization will result in **_high_** phosphate in the blood
Bone mineralization moves phosphate from serum -\> bone
69
What are the major causes of hypercalcemia?
* **Parathyroid mediated (too much PTH)**
* **Non-parathyroid mediated**
* Malignancy
* Vitamin D intoxication
* Chronic granulomatous disease
* **Medications**
* Thiazides
* Lithium
* Misc
* Hyperthyroid
* **Immobilization**
* Milk alkali syndrome
70
What is the effect of androgens (testosterone) on Ca2+ homeostasis?
Testosterone = increased bone formation
Promotes the movement of Ca2+ from the serum to the bone
71
What is secondary hypothyroidism?
What are the most common causes?
Secondary hypothyroidism = hypocalcemia in the setting of high PTH
(PTH is not doing its job increasing serum Ca2+ - think of this like reduced *effect* of PTH, rather than low PTH)
**Causes:**
* Vitamin D deficiency
* Loss of Ca2+ from the circulation
* Ca2+ is being used up by something else
* Drugs or medications that affect Ca2+ binding
* Disorders of Mg2+ metabolism: Low Mg2+ leads to low Ca2+
* Mg2+ is preferentially reabsorbed, resulting in decreased Ca2+ reabsorption
72
Describe the clinical presentation of hypercalcemia
* **Painful bones**
* Weakness, bone pain, osteopenia
* **Renal stones**
* Polyuria, nephrolithiasis, AKI
* **Abdominal groans**
* Nausea, vomiting, constipation, pancreatitis
* **Psychic moans**
* Confusion, fatigue
* Heart
* Bradycardia, short QT
73
Describe the management of hypocalcemia
* Ca2+ supplementation
* Thiazide diuretics
* Increase Ca2+ reabsorption
* Treat the underlying cause
* Replenish Mg2+ or vitamin D if necessary
* Stop drugs that are binding Ca2+
74
Is the lumen in thick ascending limb of the loop of Henle positively charged or negatively charged?
Why?
Positively charged
* The K+/Na+/2Cl- cotransporter (NKCC2) in the apical membrane gets these ions from the lumen to the epithelial cell is electrically neutral, but **ROMK in the apical membrane pumps K+ into the lumen to recycle it**
* This creates a **positively charged lumen**
* Creates an electrical gradient that **pushes Ca2+ through** **claudin 16** into the interstitium (Drives Ca2+ reabsorption)
75
How do bisphosphates treat hypercalcemia?
Bisphosphates inhibit osteoclast-mediated bone resorption
(Prevents mobilization of Ca2+ from bone -\> serum)
76
How do PTH and FGF-23 affect 1-alpha-hydroxylase activity?
* **PTH** **stimulates 1 alpha hydroxylase**
* Works to create more active vitamin D3
* -\> Works to increase serum Ca2+
* **FGF-23 inhibits 1 alpha hydroxylase**
* Works to decrease active vitamin D3
* Increased synthesis of the waste product
24,25-OH2-D3
* -\> Decrease serum Ca2+
*
77
If serum phosphorous levels are high, how would you expect FGF-23 levels to change?
High serum phosphorous
* -\> **Increased FGF-23**
* -\> decreased reabsorption of phosphorous
* **-\> Increased excretion of phosphorous**
78
What percentage of Ca2+ absorption in the intestine is through paracellular transport?
5%
79
Describe the process of Ca2+ reabsorption in the DCT
Very similar to Ca2+ reabsorption in the **intestine**
Difference = **PTH has a direct effect on Ca2+ reabsorption in the kidney**
* **TRPV5:** Lumen -\> Epithelial cell
* **Calbindin:** Luminal side of cell -\> basolateral side of cell
* **Na+/Ca2+ exchanger and Ca2+ ATPase:** Basolateral side of the cell -\> interstitium
* Both are active transport mechanisms
80
What drives Ca2+ reabsorption in the thick ascending limb?
Positive charge in the lumen
* Created by K+ secretion through ROMK
* This pushes Ca2+ reabsorption via paracellular transport
81
Where in the body is biologically active phosphorous in the body found?
In the blood
82
What is the typical picture of a chronic kidney disease patient?
* **Phosphate:**
* **FGF23:**
* **Active Vitamin D:**
* **Calcium:**
* **Phosphate:** high
* **FGF23:** high
* **Active Vitamin D:** low
* **Calcium:** low
83
PTH will ___________ production of 1,25-OH2 Vitamin D3 (active) by [stimulating/inhibiting] \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
PTH will **_increase_** production of 1,25-OH2 Vitamin D3 (active) by **_stimulating 25 alpha hydroxylase_**
84
What are the functions of phosphorous in the body?
* Phosphorous is a **part of ATP**; we need it for energy and metabolism
* It is super important for **cell function**
* Helps **RBCs carry oxygen**
* Minor role in blood buffering system for acid-base balance
* Structural component of bone and teeth when combined with Ca2+
85
How does 25-OH-D3 get into the proximal tubular cells of the kidney?
Megalin-mediated endocytosis
25-OH-D3 bound to D binding protein in the blood is not freely filtered through the glomerular filtration barrier
86
Describe the process of Calcium absorption in the intestine
* **TRPV6:** Lumen -\> intestinal epithelial cell
* **Calbindin:** Luminal side of cell -\> serum side of the cell via
(still stays inside of the intestinal epithelial cell)
* **Ca2+ ATPase or Na+/Ca2+ exchange:**
Serum side of the cell -\> serum
* Both are active transpor mechanisms; Intracellular [Ca2+] is lower than extracellular [Ca2+]
87
What is the effect of PTH on Ca2+ homeostasis?
PTH is the major regulator of Ca2+ movement in and out of the bones
* **Hypocalcemia** -\> PTH secretion -\> increased Ca2+ resorption from the bones -\> Ca2+ levels return to normal
* **Hypercalcemia** -\> Decreased PTH secretion -\> more bone formation
88
How does chronic kidney disease affect phosphorous homeostasis?
How does this effect Vitamin D, Calcium, PTH, and FGF23?
Chronic kidney disease -\>
* Reduced renal phosphate clearance
* -\> Hyperphosphatemia
* -\> **Increased FGF-23** + **Decreased 1,25-OH2-D3** synthesis
* Increased FGF-23 further reduces 1,25-OH2-D3 synthesis
* -\> **Reduced renal Ca2+ reabsorption and GI absorption**
* -\> **Hypocalcemia**
* -\> **Increased PTH** in response to hypocalcemia, but without increase in Ca2+ levels
* = secondary hyperparathyroidism
