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SM 198 Flashcards

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1
Q

Is calcium widely or narrowly distributed in the body?

A

Calcium is widely distributed in the body

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2
Q

What type of serum calcium is relevant and regulated?

A

Ionized Calcium is regulated because it is biologically active

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3
Q

What is the largest reservoir of Calcium in the body?

A

Bone

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4
Q

Where is dietary calcium primarily absorbed?

A

The Duodenum and Jejunum of the Small Intestine via active and passive processes, dependent on gastric acid

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5
Q

Is dietary calcium absorption a passive or active process?

A

Both, and it’s gastric acid dependent

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6
Q

How might Omeprazole effect Calcium absorption?

A

Omeprazole is a PPI, which lowers acid secretion into the stomach, and therefore lowers Calcium absorption due to the loss of stomach acid

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7
Q

Does Vitamin D increase or decrease intestinal phosphorus absorption?

A

Vitamin D increases intestinal phosphorus absorption

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8
Q

Where and how does Calcium reabsorption occur in the Kidneys?

A

In the Kidneys, Calcium is reabsorbed passively in the PCT and actively in the TALH and DCT

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9
Q

What factors enhance renal reabsorption of Calcium?

A

PTH and Vit D increase reabsorption of Calcium

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10
Q

How does Calcium regulate PTH production?

A

The Calcium Sensing Receptor binds excess serum Calcium when Calcium levels are high, and reduces GI absorption of Calcium as well as renal reabsorption of Calcium, while also reducing PTH production

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11
Q

What is the largest reservoir of Calcium?

A

Bone

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12
Q

How and when is Calcium extracted from bones?

A

Calcium is resorped from bone when Calcium levels are low through the action of PTH

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13
Q

What is the largest reservoir of Phosphate?

A

Bone (also biggest reservoir of Calcium)

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14
Q

Where is the major source of Phosphorous reabsorption?

A

The Jejunum of the Small Intestine

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15
Q

What channel in the GI tract is involved in Phosphorous transport?

A

The NaPi 2b channel, which actively transporters Phosphorus in a Sodium dependent manner

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16
Q

How does Vit D effect GI absorption of phosphorus?

A

Vit D enhances GI absorption of Phosphorus

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17
Q

Where is most phosphorus reabsorbed in the Kidney?

A

Most phosphorus is reabsorbed in the PCT

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18
Q

What channels mediate phosphorus reabsorption int he PCT?

A

The NaPi 2a and 2c channels mediate active reabsorption of phosphorus

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19
Q

What decreases renal reabsorption of Phosphorus?

A

PTH and FGF23

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20
Q

What produces FGF23?

A

Bone

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21
Q

What are the effects of PTH on reneal reabsorption of Phosphorus?

A

PTH decreases renal reabsorption of Phosphorus

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22
Q

What are the effects of FGF23 on renal reabsorption of Phosphorus?

A

FGF23 decreases renal reabsorption of Phosphorus

“FGF is a FosFate inhibitor”

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23
Q

What hormone is measured to broadly classify the types of hypercalcemia?

A

PTH - in theory, PTH should be low in the setting of high Calcium, but Hypercalcemia can result in the setting of both high and low PTH

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24
Q

Does high or low PTH cause hypercalcemia?

A

Both - Hypercalcemia can broadly be categorized as high or low PTH Hypercalcemia

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25
What test should be done if Hypercalcemia is found in the setting of high PTH?
Measure the Urine Calcium/Creatinine; If low, Familial Hypocalcuric Hypercalcemia If high, Primary Hyperparathyroidism
26
What should be done if Hypercalcemia is found in the setting of low PTH?
Measure PTHrP and Vitamin D levels
27
What is PTHrP?
An analog of PTH often secreted by tumors that mimics the effects of PTH and causes hypercalcemia
28
What does a high PTHrP suggest?
Cancer
29
What can cause high levels of Vitamin D and Hypercalcemia?
Sarcoid (proliferation of monocytes which can activate Vit D via 1-hydroxylase) Granulomatous disorders
30
What should be done if elevated Vitamin D precursors are found in the setting of Hypercalcemia?
Suggests too much dietary intake of Vitamin D, so restrict Vitamin D consumption
31
What can cause hypocalcemia?
Loop diuretics and Hypomagnesemia
32
What serum level indicates hyperphosphatemia?
Serum phosphate > 4.5 mg/dL
33
What could cause true hyperphosphatemia in the setting of normal kidney function?
Hypoparathyroidism (elevated PTH) FGF23 deficiency Bisphosphonates
34
What could cause false hyperphosphatemia in the setting of normal kidney function?
Paraproteinemia Hyperlipidemia Amphotericin B
35
What could cause hyperphosphatemia in the setting of decreased kidney function?
Excessive phosphate intake, rhabdomyolysis, hemolysis
36
What are bisphosphonates?
Bisphosphonates are a class of drugs that prevent the breakdown of bone and increase phosphate levels, potentially causing hyerphosphatemia
37
What could cause hypophosphatemia?
Shifts into cells, decreased intake, and renal loses
38
What factors regulate Calcium and Phosphate homeostasis?
PTH Vitamin D FGF23 Calcitonin
39
How does PTH effect bones and Calcium levels?
PTH promotes bone resorption, ie moving Calcium from bone to serum
40
How does PTH effect renal handling of Calcium?
PTH promotes renal reabsorption of Calcium
41
How does PTH effect bones and Phosphate levels?
PTH promotes bone resorption, ie moving Phosphate from bone to serum
42
How does PTH effect renal handling of Phosphate?
PTH inhibits renal reabsorption of Calcium
43
In what organ does PTH have the same effect on Phosphate and Calcium?
PTH promotes Phosphate and Calcium resorption in bone, raising serum levels of both
44
In what organ does PTH have opposing effects on Phosphate and Calcium?
PTH promotes Calcium reabsorption in the Kidneys to raise serum Calcium levels PTH inhibits Phosphate reabsorption in the Kidneys to lower serum Phosphate levels
45
What is Calcitriol?
The man made active form of Vitamin D
46
What hormone promotes Ca and Phosphate reabsorption from the GI tract?
Calcitriol/Vitamin D
47
What effect does Vitamin D have on renal handling of Calcium?
Vitamin D promotes reabsorption of Calcium, raising serum levels
48
What effect does Vitamin D have on renal handling of Phosphate?
Vitamin D promotes reabsorption of Phosphate, raising serum levels
49
What effect does Calcitonin have on bone, Calcium, and Phosphate?
Calcitonin inhibits reabsorption of Calcium and Phosphate from bone, lowering serum Ca and Phosphate
50
What organ produces Calcitonin?
Calcitonin is produced by the Thyroid gland
51
What are common functions of Calcium?
Forms bones and teeth Neurotransmission Muscle contractility Signaling
52
Normal calcium homeostasis involves absorbing 300mg/day from the GI tract and excreting 150mg/day - why?
Allows for fine tuning of Ca intake
53
What are the 3 forms of Calcium in blood?
Ionized Ca (biologically active) Protein bound Ca Ca complexed with Citrate/Bicarb/Phosphate
54
How does Alkalemia effect serum Calcium levels?
Alkalemia increases protein binding of Calcium, decreasing the ionized Calcium fraction, without altering total Calcium Symptoms of Hypocalcemia occur because ionized Calcium decreases
55
How does changes in Albumin change the bound fraction of Calcium?
Increasing Albumin levels results in more Ca bound to Albumin, but does not change the ionized Calcium Symptoms of Hypocalcemia do not occur
56
Why do nephrotic syndromes not change the serum Calcium?
Nephrotic syndromes lose the charge barrier at the Glomerulus and therefore lose Albumin + bound Ca, but the serum Ca remains unchanged Symptoms of Hypocalcemia do not occur
57
How does Vitamin D regulate Calcium absorption in the Intestine?
In the Intestine: Vitamin D binds the Vitamin D Receptor on the basolateral membrane and forms a complex Complex translocates to Nucleus Expression of Na/Ca exchanger and Ca ATPase on Apical side facing blood is increased
58
How does the Ca sensing receptor effect Vitamin D signaling in the intestine?
Ca Sensing Receptor detects hypercalcemia and inhibits Vitamin D signaling
59
How does Calcium get absorbed in the intestine?
Calcium from the diet binds the TRPV6 receptor on the Apical membrane Calcium binds the Calbindin protein and gets moved from the Apical membrane to the Basolateral membrane Calcium is then exported out of the intestinal cell via the Na/Ca exchanger and the Ca ATPase
60
How does Calcium get exported out of the intestine?
Calcium is released into the blood via the Na/Ca exchanger and Ca ATPase on the Apical membrane
61
Why does it take ATP to move Calcium out of the intestine and into the blood?
Calcium concentrations are higher in the blood than the intestinal cell, so it takes ATP to pump it out
62
Does paracellular absorption play a role in Calcium uptake in the intestine?
Yes, but a very small role (5%)
63
Why does Calcium intake saturate in the intestine?
The Ca Sensing Protein detects hypercalcemia and inhibits Vit D as well as further Ca absorption
64
Where in the intestine does Calcium get absorbed?
Duodenum and Jejunum
65
How does pancreatic insufficiency effect Calcium absorption?
Pancreatic insufficiency leads to Fat in the blood which binds Calcium and lowers serum Calcium
66
How do Androgens and Estrogens effect Bone?
Androgens and Estrogens have the same effect on bone but with different mechanisms, ultimately lowering serum Ca
67
How do Androgens and Estrogens differ on Bone?
Androgens promote Bone formation, Estrogens inhibit Bone Resorption Both lower Serum Ca
68
How does immobilization effect bones?
Immobilization decreases bone formation and raises serum Ca
69
How much Calcium is excreted?
Very little (3%)
70
How does Hypocalcemia effect the TALH?
Hypocalcemia stimulates PTH PTH stimulates Claudin permeability Ca and Mg paracellular reabsorption through Claudin increases Hypocalemia is then corrected
71
What does PTH do in the TALH?
PTH stimulates Claudin and increases paracellular transport of Ca and Mg
72
How does the CaSR mediate the TALH?
CaSR binds Calcium under Hypercalcemia CaSR inhibits Claudin and ROMK Loss of K leak through ROMK = no positive lumen to drive Ca/Mg paracellular transport CaSR makes Claudin less permeable = inhibit Ca/MG paracellular transport CaSR results in decreased paracellular transport of Ca and Mg
73
Is the NKCC channel electrogenic?
No, 2 positive charges from Na and K are cancelled out by 2 negative charges from Cl
74
What effect does PTH have on the GI Tract?
None, PTH only effects the Kidney and Bones
75
How does PTH regulate the DCT?
PTH binds to it's receptor and increases Calbindin activity and Calcium uptake
76
How does the CaSR effect the DCT?
The CaSR binds Calcium and activates the Np2a phosphate transporter to promote Phosphate reabsorption
77
How does FGF23 regulate phosphate reabsorption in the kidney?
FGF23 binds the FGF Receptor on the apical membrane FGF23 bound to FGFR interacts with Klotho on the membrane FGF + FGFR + Klotho inhibits NaPi-mediated absorption of phosphate
78
Describe the pathway for Vitamin D activation?
7-dehydrocholesterol from the body is converted to pre-vitamin D3 by UV light Pre-vitamin D3 is converted into 25 OH Vit D3 in the liver by 25 alpha hydroxylase 25 OH Vit D3 is bound to the D-binding protein and crosses the Glomerulus PCT cells take up DBP + 25 Vit D3 via Absorptive Endocytosis 25 Vit D3 is either activated by 1 alpha Hydroxylase or inactivated by 24 alpha Hydroxylase
79
How does Vit D3 cross the glomerular membrane?
Vit D3 bound to D binding protein crosses the Glomerulus and is taken up by PCT cells via absorptive endocytosis
80
Which PCT enzyme activates Vit D3?
1 alpha Hydroxylase
81
Which PCT enzyme inactivates Vit D3?
24 alpha Hydroxylase
82
What effect does PTH have on the PCT?
PTH activates 1 alpha Hydroxylase to promote Vit D activation
83
What effect does FGF23 have on PCT?
FGF23 inhibits 1 alpha Hydroxylase to inhibit Vit D activation
84
What is the major negative regulator of PTH?
Calcium, due to signaling via the CaSR on the Parathyroid Chief Cell
85
Why does Vitamin D negatively regulate PTH?
PTH activates Vitamin D so Vitamin D negatively regulates PTH in a form of negative feedback
86
What class of medication can cause hypercalcemia?
Thiazides
87
How does hypercalcemia present?
Bones, Stones, Groans, Thrones, Moans
88
Which class of diuretics should be used to treat hypercalcemia?
Loop diuretics, which promote calcium loss
89
Which type of fluid should be used to treat hypercalcemia?
Sodium containing IV fluids
90
How can a lack of sunglight lead to hypocalcemia?
Vitamin D deficiency, due to lack of UV light to activate 7-dehydrocholesterol
91
How does tumor lysis syndrome cause hypocalcemia?
Dying tumor cells release phosphate which sequesters calcium in the serum and causes hypocalcemia
92
What are clinical manifestations of hypocalcemia?
Tetany, twitches, bone fractures, hypocoagulable state
93
What is chvosteks sign?
Tapping the facial nerve results in a contraction of the facial muscle
94
How should hypocalcemia be treated?
Supplement calcium and thiazide diuretics?
95
How can urine sedimentation reveal whether or not elevated protein is causing false hyperphosphatemia?
Spinning down the urine will show a larger protein band, suggesting that hyperphosphatemia is due to more protein and not true hyperphosphatemia
96
What ionic changes accompany CKD?
Increased phosphate Increased PTH Increased FGF23 Decreased Ca
97
What disorders can cause metastatic calcifications?
Hypercalcemia | Hyperphosphatemia
98
What are symptoms of hyperphosphatemia?
Itching and metastatic calcifications
99
How should hyperphosphatemia be managed?
Phosphorous binders like Sevelamer | Low phosphorous diet
100
Why does refeeding after a period of malnutrition lead to hypophosphatemia?
Food intake results in ATP production which uses up the phosphate in the blood, causing hypophosphatemia
101
What are the clinical manifestations of hypophosphatemia?
Arrhythmias, lethargy, bone demineralization
102
How should hypophosphatemia be treated?
IV phosphate or food, treat underlying cause

Renal (19 decks)

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