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

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Flashcards in 05.15 - Calcium, Phosphate Metab (Kovesdy) - PP, no reading Deck (83):
1

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

80-97%, 80% of this in PT

1

How does hypocalcemia affect Vit D

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

2

4 Major Consequences of CKD-MBD

Renal Osteodystrophy, Fractures, Calcification, CV Disease

3

Phosphate and Vit D in secondary HPT in CKD

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

3

FGF-23 directly inhibits

1a-Hydroxylase

4

How does VDR activation affect PTH levels

Higher activation = Lower PTH

5

Effect of Vit D on PO4

Incr reabsorption in gut; Decr reabsorption in kidney

5

Why are FGF19, 21, and 23 unique

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

5

Hereditary Tumoral Calcinosis is disorder of

FGF23 Deficiency

7

Ratio of Fecal Loss vs Urine Loss of Phosphorus

500 to 900

7

Disorder of FGF23 excess is called

Hereditary/Acquired Hypo-Phosphatemic Rickets

8

Change in serum calcium in CKD

Decreases

9

Hereditary/Acquired Hypo-Phosphatemic Rickets is a disorder of

FGF23 Excess

10

First, or one of the first, markers in CKD

FGF-23

11

2 factors that play a role in calcium absorption

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

11

Pitfalls of Serum Ca2+ measurement

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

12

Bones in FGF23 excess vs deficiency

Rickets/Osteomalacia in excess; Hyperosteosis in deficiency

13

High ___ mileu may potentiate Calcium fluxes in CKD

phosphorus

13

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

Hypophosphatemia (Osteomalacia)

13

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

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

13

Effect of FGF-23 on Heart

LV Hypertrophy

14

How does bone metabolism affect FGF-23

Osteocytes and osteoblasts secrete FGF-23

15

FGF-23 is involved in

Phosphate and Vit D homeostasis

17

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

False, 10-20 times higher

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