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Renal > 05.15 - Calcium, Phosphate Metab (Kovesdy) - PP, no reading > Flashcards

05.15 - Calcium, Phosphate Metab (Kovesdy) - PP, no reading Flashcards

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1
Q

Percent of Phosph Filtered Load that is reabsorbed? What contributes to most of this reabsorption?

A

80-97%, 80% of this in PT

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1
Q

How does hypocalcemia affect Vit D

A

Stimulates PTH –> Stimulates 1a-Hydroxylase -> Incr 1,25 production by kidneys

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2
Q

4 Major Consequences of CKD-MBD

A

Renal Osteodystrophy, Fractures, Calcification, CV Disease

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3
Q

Phosphate and Vit D in secondary HPT in CKD

A

Vitamin D deficiency –> Phosphate retention (lower capacity to secrete Phosphate in kidney)

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3
Q

FGF-23 directly inhibits

A

1a-Hydroxylase

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4
Q

How does VDR activation affect PTH levels

A

Higher activation = Lower PTH

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5
Q

Effect of Vit D on PO4

A

Incr reabsorption in gut; Decr reabsorption in kidney

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5
Q

Why are FGF19, 21, and 23 unique

A

Don’t need Heparin, so can circulate and act as endocrine factors (rather than paracrine)

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5
Q

Hereditary Tumoral Calcinosis is disorder of

A

FGF23 Deficiency

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7
Q

Ratio of Fecal Loss vs Urine Loss of Phosphorus

A

500 to 900

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7
Q

Disorder of FGF23 excess is called

A

Hereditary/Acquired Hypo-Phosphatemic Rickets

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8
Q

Change in serum calcium in CKD

A

Decreases

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9
Q

Hereditary/Acquired Hypo-Phosphatemic Rickets is a disorder of

A

FGF23 Excess

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10
Q

First, or one of the first, markers in CKD

A

FGF-23

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11
Q

2 factors that play a role in calcium absorption

A

Amount of intake, amoung of 1,25(OH)2 Vit D

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11
Q

Pitfalls of Serum Ca2+ measurement

A

Assay measures total, but 40% of Ca is bound to albumin, and only free and ionized Ca is biologically active

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12
Q

Bones in FGF23 excess vs deficiency

A

Rickets/Osteomalacia in excess; Hyperosteosis in deficiency

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13
Q

High ___ mileu may potentiate Calcium fluxes in CKD

A

phosphorus

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13
Q

What is consequence of maintaining 1,25(OH)2 levels with Vit D deficiency

A

Hypophosphatemia (Osteomalacia)

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13
Q

FGF-23 correlation with Phosphorus in Norma vs CKD/ESRD

A

in normal, higher fgf-23 = lower PO4; in ckd, higher fgf-23 = higher PO4

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13
Q

Effect of FGF-23 on Heart

A

LV Hypertrophy

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14
Q

How does bone metabolism affect FGF-23

A

Osteocytes and osteoblasts secrete FGF-23

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15
Q

FGF-23 is involved in

A

Phosphate and Vit D homeostasis

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17
Q

T/F: CVD mortality rates are 5 times higher in Stage 5 CKD patients than general population

A

False, 10-20 times higher

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17
How does 1,25(OH)2 affect FGF-23
Increase FGF-23
18
Similar to Phosphate, extracellular pool is only ____ proportion of total body Ca
Small
19
Consequences of Hypercalcemia
CV and Soft Tissue Calcification
20
Diffuse calcification of tunica media causes what pathophysiology
High pulse wave velocity
21
T/F: Tubular reabsorption of Phosphate is unsaturable
FALSE
23
How does PTH affect Vit D
Incr 1a-hydroxylation of Vit D
23
Urinary Ca excretion in CKD
Marked decr in Ca excretion with advancing states of CKD
23
1,25(OH)2 in Vit D Deficiency: normal kidney vs CKD
Normal or increase in normal kidney patient; Low in CKD patient
25
Key regulator of Ca absorption
Active Vit D
26
Clinical features of FGF23 excess
Low serum Phosphate, Aberrant Vit D, Rickets/Osteomalacia
27
Phosphate in FGF23 excess vs deficiency
Low in excess, high in deficiency
29
Main pathophysiology seen in patients on dialysis
Increased pulse wave velocity
30
The higher the level of Ca in dialysis patients, the higher the
Mortality rate
31
Most patients with normal kidney fxn who are vit d deficient have what levels of 1,25
Normal or increased (paradoxically, because missing precursor
33
At what GFR will you see major changes in Phosphorus and Calcium
Not until less than 30 (GFR)
33
Consequence of Hypocalcemia
Increased neuromuscular excitability
35
Ratio of Fecal to Renal loss for Calcium
700 mg/dL to 300 mg/dL
36
How does Calcitrol aka 1,25(OH)2 Vit D affect transcription
Binds with VDR nuclear receptor in cytoplasm, dimerizes with RXR, and both bind Vit D response element
36
Effect of FGF-23 on RAAS, Klotho, Inflammation
Inc RAAS, Dec Klotho, Inc Inflammation
38
Klotho is necessary for
FGF23
39
Effect of FGF23 on PTH, 1a-Hydroxylase
Inhibits both
40
In Vit D deficiency with CKD, PTH cannot stimulate \_\_\_, leading to def in \_\_\_\_
1a-Hydroxylase, deficiency in 1,25(OH)2
42
Main reason hyperphosphatemia is detrimental
Phenotypically, vascular SM cells turn to bone
44
Does Ca2+ level affect mortality
Yes, higher Ca2+ means much higher mortality rate
45
Clinical features of FGF23 deficiency
Hyperphosphatemia, Elevated Calcitrol, Soft tissue calcifications, Hyperosteosis
47
What percent of phosphorus is in ECV? Soft tissue? Bone?
1%, 14%, 85%
48
T/F: Albumin-adjusted serum Ca levels correlate well with ionized Ca in CDK and ESRD
False, correlate poorly - don't adjust for Albumin
49
Normal Phosp plasma conc.
3-4.5 mg/dL
50
Serum phosphorus in stage 5 CKD
Predictably elevated
51
Calcium in what state is actually active
Free (unbound to Albumin) and ionized
52
With GFR \> 40, TmPhosphate ___ with GFR
TmP Varies proportionately with GFR
54
How does primary decr of Ca affect PTH
Increases PTH
55
Calcium balance in CKD
If diet is low in calcium, neutral balance; If diet is high in calcium, more positive balance than controls (they are more sensitive)
56
How does Ca affect PTH
Hypocalcemia stimulates PTH production
57
Cofactor for FGFs (except 19, 21, 23)
Heparin
58
Effect of PTH on Bone
Increase reabsorption --\> Incr Ca and PO4
59
Vit D deficiency patients with normal kidney function
Normal 1,25(OH)2 but at expense of Hypophosphatemia (osteomalacia)
60
PO4 in Vit D deficiency: normal kidney vs CKD
Low in normal patient, high in CKD patient
61
How and where is Vitamin D3 converted to 25(OH)
In liver by 25-hydroxylase
62
Change in serum phosphorus in CKD
Increases
63
First, or one of the first, regulators when GFR lost
FGF-23
65
With GFR \< 40, TmPhosphate \_\_\_\_
Further decreases, but decrease is less than decrease in GFR = Hyperphosphatemia ensues
66
Effect of Calcitrol supplementation on longevity
Improves
67
Calcification seen in CKD vs general population
Medial vs Intimal
68
Vit D in FGF23 excess vs deficiency
Low in excess, high in deficiency
69
FGF-23 levels in ESRD
Markedly elevated
70
If you try to explain bone mineral metabolism with PTH, you run into trouble with
Phosphorus - PTH both increases and decreases PO4
71
Effect of PTH on PO4
Incr thru bone and gut via Vit D, Decr reabsorption in kidney (opposing effects)
72
Dialysis greatly increases deposits of what in coronary arteries
Calcium
74
Why do you get Hyperphosphatemia with low GFR
With GFR less than 40, TmPO4 further decreases, but decrease is less than decrease in GFR
75
Hyperphosphatemia initiates a cascade of events that results in
Calcification of vascular SM cells
76
How does PTH affect gut absorption
Enhances absorption of Ca and PO4 thru increased Vit D
77
Association of serum phosphorus to mortality in dialysis patients
Higher mortality with higher phosphate levels (and very low levels)
78
FGF vs PTH as marker for PTH
Both good, but FGF-23 earlier
79
PO4, FGF-23, ALP, PTH in CKD, MBD
All increase
80
Disorder of FGF23 deficiency is called
Hereditary Tumoral Calcinosis
81
How and where is 25(OH) Vit D converted to 1,25(OH)2 Vit D
By 1a-Hydroxylase most in tissues but also in kidney
82
Consequences of increased pulse wave velocity due to dialysis calcification
Inc afterload -\> LVH; Decr coronary perfusion pressure; Incr Myocardial O2 demand; Incr endothelial dysfunction and atherogenesis
83
Phosphate imbalance with low GFR
Hyperphosphatemia

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