05.08 - Disorders of PCT, Water (Gosmanova) - PP, No reading Flashcards Preview

Renal > 05.08 - Disorders of PCT, Water (Gosmanova) - PP, No reading > Flashcards

Flashcards in 05.08 - Disorders of PCT, Water (Gosmanova) - PP, No reading Deck (88):
1

Hormonal Function of PT

Final pathway in synthesis of active Vit D

1

Isolated PT dysfunctions are rare but typically result from

disorder of specific transport proteins

2

Mutation in AR Hypo-P Rickets

Several leading to increased FGF-23; or Na-Pi Iic transporter

3

What is Oncogenic Hypo-P Osteomalacia

Inc. production of FGF-23 by some tumors: fibromas, angiosarcomas, hemangiopericytomas

3

2 ways ADH regulates AQP-2

Short-term: reversibly shuttles channel to luminal membrane; Long-term: inc transcription of AQP-2 gene

4

Plasma Na ~

(Total Body exchangeable Na and K) / TBW

5

What causes Vit D-dependent Rickets Type 1

Mutation of 1alpha-Hydroxylase

6

Mutation in PHEX results in increased

levels of circulating factor FGF-23 (PHEX normally downregulates)

6

When is Normal Osmolarity Hyponatremia likely to occur

HyperTGemia, Paraproteinemia - when solid phase of plasma is greatly increased

7

To which is ADH release more senstive, Posm increase or decrease in BV

Posm increase: 1% increase in Posm triggers, but takes 7% decrease in BV to trigger

8

Hypernatremia usually develops if

Thirst is impaired or limitation in acess to free water

9

FGF-23 inhibits

Na-Pi cotransporter and alpha-1-hydroxylase

9

What causes Hartnup Disease

Defect in neutral AA transporter (SLC6A19)

9

Most important inherited cause of Fanconi Syndrome

Cystinosis - Cysteine not degraded normally

9

Main defence mechanism against hypernatremia

Thirst

10

Generalized PT dysfunctions are usually accompanied by

cause-specific extra-renal manifestations

11

Changes in Plasma Na are mainly determined by changes in

TBW

12

Normal Posm

285-290 mOsm/kg

12

When is Dilutional Hyponatremia likely to occur?

Glucose in absence of insulin, Mannitol, Glycine

13

Polyuria is defined as

Incr in urine volume > 3L/day

14

__ is always present in True Hyponatremia

Impaired urinary dilution mechanisms

15

How does increase in peritubular capillary hydrostatic pressure affect net reabsorption of Na and water

Reduces

16

Glomerulotubular Balance is the intrinsic ability of tubules to increase reabsorption in response to

Incr tubular load

18

Macro structure of PT epithelial cells

Microvili (brush border); Basolateral surface is thrown into folds - both extend surface area

19

Inc production of FGF-23 by some tumors

Oncogenic Hypo-P Osteomalacia

19

Non-osmotic stimuli that stimulate ADH release

Dec ECV, Nausea, Pain, Drugs, Corticosteroid deficiency

19

In absence of ADH, urinary osmolarity can be lowered to

40-60 mOsm/kg

21

Ang 2 regulates ___ reabsorption and ___ secretion

NaCl and H20; H+ secretion

22

How is insulin taken up by PT cells

Pinocytosis

23

Water Excess =

0.6 x TBW x (1 - [Na]/140)

24

Most common inherited phosphate wasting disorder

X-Linked Hypophosphatemic Rickets

24

Osmotic threshold for thirst vs ADH

Slightly higher for thist: 290-295 vs 280-290

24

Hyponatremia with volume depletion is caused by

Renal, GI, or Skin losses; Third spacing

25

4 Acquired forms of Nephrogenic DI

(1) Defect in medullary interstitial tonicity; (2) Defect in cAMP generation; (3) AQP-2 downreg; (4) Pregancy

26

Cause of Cystinuria

Mutation of brush border transporter responsible for cysteine, and other AA's

27

Relationship of PHEX, FGF-23, and Na-Pi cotransporter

PHEX inhibits FGF-23, and FGF-23 inhibits Na-Pi cotransporter and Alpha1-Hydroxylase production

28

Proximal Straight Tubule is aka

Parse Recta

30

Reabsorption in PT is dependent on

Volume Status

31

Serum Glucose in Hereditary Renal Glucosuria

Normal

32

Mutation of brush border transporter responsible for cysteine, and other AA's

Cause of Cystinuria

32

2 most important acquired causes of Fanconi Syndrome

Tenofovir, Multiple Myeloma

33

How does X-Linked Hypophosphatemic Rickes present clinically

Rickets in children; Osteomalacia in adults

33

Hyperosmolar Hyponatremia is due to

Presence of other osmotically active substances that cause water movement out of cells = Dilutional Hyponatremia

34

True Hyponatremia occurs as a result of

Incr TBW, either absolute or relative

36

Mutation in X-linked Hypophosphatemia

PHEX

37

___ is present in majority of cases of true hyponatremia

Appropriate or inappropriate increase in ADH

39

Phosphate vs Na: One can be reabsorbed transcellular and para, the other only trans

Phosphate is trancellularly reabsorbed, Na can be either.

40

3 functional segments of PT

S1-initial short segment; S2-remaining PCT and cortical parse recta; S3-medullary parse recta

42

Severity of Cystinuria

Relatively benign, rarely causes kidney failure

44

Hereditary Renal Glucosuria is caused by

mutation of SGLT2 Glucose transporter

44

FGF-23 normally inhibits

Na-Pi cotransporter

46

Classifications of PT dysfunction based on mechanism

Generalized vs Isolated Solute Transport Disorders

48

Inheritance of Hereditary Renal Glucosuria

Autosomal recessive

49

Water Deficit =

0.6 x TBW x ([Na]/140 - 1)

50

Hyponatremia with Volume Overload is caused by

Decreased ECV: CHF, Kidney failure, Cirrhosis, Nephrotic

51

Normal function of PHEX

Downregulate FGF23

53

Parathyroid hormone regulates what in PT

Pi excretion

54

Normal osmostic threshold for ADH release

280-290 mOsm/kg

56

Fanconi Syndrome can be __, but is most commonly ___

Inherited, but most commonly acquired

58

Susceptibility of PT to ischemia

High

59

Osmotic threshold for thirst

290-295 mOsm/kg (slight higher than for ADH)

60

Patient with functional SGLT2 will have glucosuria if

[Glu] exceeds normal threshold

61

How does pregnancy cause Nephrogenic DI

Placental synthesis of Vasopresinase

62

Uosm in response to water deprivation in Primary Polydipsia

Increase

63

Congenital Nephrogenic DI results from mutations in

V2 or Aquaporin 2

64

Cwater =

V x (1 - Uosm/Posm) = V - Cosm

65

Normal Osmolarity Hyponatremia is due to

Limitation of some Na assays when Na is measure in the whole plasma while solid phase of plasma is greatly increased (eg. HyperTGemia, Paraproteinemia)

67

3 inherited causes of Isolated Phosphate Reabsorption defect

(1) X-linked hypophosphatemia; (2) AD Hypophosphatemic Rickets; (3) AR Hypophosphatemic Rickets

68

Acquired cause of Isolated Phosphate Reabsorption defect

Oncogenic Hypophosphatemic Osteomalacia

69

Cosm =

Uosm/Posm x V

70

Most common mutation related to phosphate reabsorption

X-Linked Hypo-P

71

Why is PT highly susceptible to ischemia

ATP dependence, Polarized structure of cells

72

K moving paracellularly is an example of

Simple diffusion requiring electrochemical gradient

73

Mutation in FGF-23

AD Hypo-P Rickets

74

In PT, 33% of Na is reabsorbed via ___, the rest by

33% via transporter proteins, the rest passively by solvent drug via paracellular route

76

Most common electrolyte disorder

Hyponatremia

77

Mitochondria in PT epithelial cells

Rich to provide sufficient energy for mass reabsorption

77

Where is 100% of glucose reabsorbed

PT

78

Mutation in AD Hypo-P Rickets

FGF-23

79

How quickly does ADH insert new AQP-2 channels

within minutes

81

Hyponatremia with normal volume status is caused by

Too much ADH (SIADH, Glucocorticoid def., Hypothyroidism)

82

Which are more severe: Generalized or Isolated PT Dysfunctions

Generalized

83

Hypoosmolar Hyponatremia is due to

Always due to impaired urinary dilution mechanisms

84

"Generalized" PT dysfunction is usually due to

Defect in energy generation (Na-K ATPase) or dysfunction of cellular organelles affecting transport recycling

85

25% of Na in PT is reabsorbed by what exchanger

Na-H

86

mutation of SGLT2 Glucose transporter

Hereditary Renal Glucosuria is caused by

87

What percent of Phosphorus is reabsorbed in PT

80%

88

FGF23 regulates what in PT

Pi excretion