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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

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
Q

How does 1,25(OH)2 affect FGF-23

A

Increase FGF-23

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18
Q

Similar to Phosphate, extracellular pool is only ____ proportion of total body Ca

A

Small

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19
Q

Consequences of Hypercalcemia

A

CV and Soft Tissue Calcification

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20
Q

Diffuse calcification of tunica media causes what pathophysiology

A

High pulse wave velocity

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21
Q

T/F: Tubular reabsorption of Phosphate is unsaturable

A

FALSE

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23
Q

How does PTH affect Vit D

A

Incr 1a-hydroxylation of Vit D

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23
Q

Urinary Ca excretion in CKD

A

Marked decr in Ca excretion with advancing states of CKD

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23
Q

1,25(OH)2 in Vit D Deficiency: normal kidney vs CKD

A

Normal or increase in normal kidney patient; Low in CKD patient

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25
Q

Key regulator of Ca absorption

A

Active Vit D

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26
Q

Clinical features of FGF23 excess

A

Low serum Phosphate, Aberrant Vit D, Rickets/Osteomalacia

27
Q

Phosphate in FGF23 excess vs deficiency

A

Low in excess, high in deficiency

29
Q

Main pathophysiology seen in patients on dialysis

A

Increased pulse wave velocity

30
Q

The higher the level of Ca in dialysis patients, the higher the

A

Mortality rate

31
Q

Most patients with normal kidney fxn who are vit d deficient have what levels of 1,25

A

Normal or increased (paradoxically, because missing precursor

33
Q

At what GFR will you see major changes in Phosphorus and Calcium

A

Not until less than 30 (GFR)

33
Q

Consequence of Hypocalcemia

A

Increased neuromuscular excitability

35
Q

Ratio of Fecal to Renal loss for Calcium

A

700 mg/dL to 300 mg/dL

36
Q

How does Calcitrol aka 1,25(OH)2 Vit D affect transcription

A

Binds with VDR nuclear receptor in cytoplasm, dimerizes with RXR, and both bind Vit D response element

36
Q

Effect of FGF-23 on RAAS, Klotho, Inflammation

A

Inc RAAS, Dec Klotho, Inc Inflammation

38
Q

Klotho is necessary for

A

FGF23

39
Q

Effect of FGF23 on PTH, 1a-Hydroxylase

A

Inhibits both

40
Q

In Vit D deficiency with CKD, PTH cannot stimulate ___, leading to def in ____

A

1a-Hydroxylase, deficiency in 1,25(OH)2

42
Q

Main reason hyperphosphatemia is detrimental

A

Phenotypically, vascular SM cells turn to bone

44
Q

Does Ca2+ level affect mortality

A

Yes, higher Ca2+ means much higher mortality rate

45
Q

Clinical features of FGF23 deficiency

A

Hyperphosphatemia, Elevated Calcitrol, Soft tissue calcifications, Hyperosteosis

47
Q

What percent of phosphorus is in ECV? Soft tissue? Bone?

A

1%, 14%, 85%

48
Q

T/F: Albumin-adjusted serum Ca levels correlate well with ionized Ca in CDK and ESRD

A

False, correlate poorly - don’t adjust for Albumin

49
Q

Normal Phosp plasma conc.

A

3-4.5 mg/dL

50
Q

Serum phosphorus in stage 5 CKD

A

Predictably elevated

51
Q

Calcium in what state is actually active

A

Free (unbound to Albumin) and ionized

52
Q

With GFR > 40, TmPhosphate ___ with GFR

A

TmP Varies proportionately with GFR

54
Q

How does primary decr of Ca affect PTH

A

Increases PTH

55
Q

Calcium balance in CKD

A

If diet is low in calcium, neutral balance; If diet is high in calcium, more positive balance than controls (they are more sensitive)

56
Q

How does Ca affect PTH

A

Hypocalcemia stimulates PTH production

57
Q

Cofactor for FGFs (except 19, 21, 23)

A

Heparin

58
Q

Effect of PTH on Bone

A

Increase reabsorption –> Incr Ca and PO4

59
Q

Vit D deficiency patients with normal kidney function

A

Normal 1,25(OH)2 but at expense of Hypophosphatemia (osteomalacia)

60
Q

PO4 in Vit D deficiency: normal kidney vs CKD

A

Low in normal patient, high in CKD patient

61
Q

How and where is Vitamin D3 converted to 25(OH)

A

In liver by 25-hydroxylase

62
Q

Change in serum phosphorus in CKD

A

Increases

63
Q

First, or one of the first, regulators when GFR lost

A

FGF-23

65
Q

With GFR < 40, TmPhosphate ____

A

Further decreases, but decrease is less than decrease in GFR = Hyperphosphatemia ensues

66
Q

Effect of Calcitrol supplementation on longevity

A

Improves

67
Q

Calcification seen in CKD vs general population

A

Medial vs Intimal

68
Q

Vit D in FGF23 excess vs deficiency

A

Low in excess, high in deficiency

69
Q

FGF-23 levels in ESRD

A

Markedly elevated

70
Q

If you try to explain bone mineral metabolism with PTH, you run into trouble with

A

Phosphorus - PTH both increases and decreases PO4

71
Q

Effect of PTH on PO4

A

Incr thru bone and gut via Vit D, Decr reabsorption in kidney (opposing effects)

72
Q

Dialysis greatly increases deposits of what in coronary arteries

A

Calcium

74
Q

Why do you get Hyperphosphatemia with low GFR

A

With GFR less than 40, TmPO4 further decreases, but decrease is less than decrease in GFR

75
Q

Hyperphosphatemia initiates a cascade of events that results in

A

Calcification of vascular SM cells

76
Q

How does PTH affect gut absorption

A

Enhances absorption of Ca and PO4 thru increased Vit D

77
Q

Association of serum phosphorus to mortality in dialysis patients

A

Higher mortality with higher phosphate levels (and very low levels)

78
Q

FGF vs PTH as marker for PTH

A

Both good, but FGF-23 earlier

79
Q

PO4, FGF-23, ALP, PTH in CKD, MBD

A

All increase

80
Q

Disorder of FGF23 deficiency is called

A

Hereditary Tumoral Calcinosis

81
Q

How and where is 25(OH) Vit D converted to 1,25(OH)2 Vit D

A

By 1a-Hydroxylase most in tissues but also in kidney

82
Q

Consequences of increased pulse wave velocity due to dialysis calcification

A

Inc afterload -> LVH; Decr coronary perfusion pressure; Incr Myocardial O2 demand; Incr endothelial dysfunction and atherogenesis

83
Q

Phosphate imbalance with low GFR

A

Hyperphosphatemia

Renal (31 decks)

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