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

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

1
Q

Hormonal Function of PT

A

Final pathway in synthesis of active Vit D

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1
Q

Isolated PT dysfunctions are rare but typically result from

A

disorder of specific transport proteins

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2
Q

Mutation in AR Hypo-P Rickets

A

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

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3
Q

What is Oncogenic Hypo-P Osteomalacia

A

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

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3
Q

2 ways ADH regulates AQP-2

A

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

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4
Q

Plasma Na ~

A

(Total Body exchangeable Na and K) / TBW

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5
Q

What causes Vit D-dependent Rickets Type 1

A

Mutation of 1alpha-Hydroxylase

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6
Q

Mutation in PHEX results in increased

A

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

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6
Q

When is Normal Osmolarity Hyponatremia likely to occur

A

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

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7
Q

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

A

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

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8
Q

Hypernatremia usually develops if

A

Thirst is impaired or limitation in acess to free water

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9
Q

FGF-23 inhibits

A

Na-Pi cotransporter and alpha-1-hydroxylase

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9
Q

What causes Hartnup Disease

A

Defect in neutral AA transporter (SLC6A19)

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9
Q

Most important inherited cause of Fanconi Syndrome

A

Cystinosis - Cysteine not degraded normally

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9
Q

Main defence mechanism against hypernatremia

A

Thirst

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10
Q

Generalized PT dysfunctions are usually accompanied by

A

cause-specific extra-renal manifestations

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11
Q

Changes in Plasma Na are mainly determined by changes in

A

TBW

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12
Q

Normal Posm

A

285-290 mOsm/kg

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12
Q

When is Dilutional Hyponatremia likely to occur?

A

Glucose in absence of insulin, Mannitol, Glycine

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13
Q

Polyuria is defined as

A

Incr in urine volume > 3L/day

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14
Q

__ is always present in True Hyponatremia

A

Impaired urinary dilution mechanisms

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15
Q

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

A

Reduces

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16
Q

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

A

Incr tubular load

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18
Q

Macro structure of PT epithelial cells

A

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

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19
Q

Inc production of FGF-23 by some tumors

A

Oncogenic Hypo-P Osteomalacia

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19
Q

Non-osmotic stimuli that stimulate ADH release

A

Dec ECV, Nausea, Pain, Drugs, Corticosteroid deficiency

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19
Q

In absence of ADH, urinary osmolarity can be lowered to

A

40-60 mOsm/kg

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21
Q

Ang 2 regulates ___ reabsorption and ___ secretion

A

NaCl and H20; H+ secretion

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22
Q

How is insulin taken up by PT cells

A

Pinocytosis

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23
Q

Water Excess =

A

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

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24
Q

Most common inherited phosphate wasting disorder

A

X-Linked Hypophosphatemic Rickets

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24
Q

Osmotic threshold for thirst vs ADH

A

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

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24
Q

Hyponatremia with volume depletion is caused by

A

Renal, GI, or Skin losses; Third spacing

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25
Q

4 Acquired forms of Nephrogenic DI

A

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

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26
Q

Cause of Cystinuria

A

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

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27
Q

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

A

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

28
Q

Proximal Straight Tubule is aka

A

Parse Recta

30
Q

Reabsorption in PT is dependent on

A

Volume Status

31
Q

Serum Glucose in Hereditary Renal Glucosuria

A

Normal

32
Q

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

A

Cause of Cystinuria

32
Q

2 most important acquired causes of Fanconi Syndrome

A

Tenofovir, Multiple Myeloma

33
Q

How does X-Linked Hypophosphatemic Rickes present clinically

A

Rickets in children; Osteomalacia in adults

33
Q

Hyperosmolar Hyponatremia is due to

A

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

34
Q

True Hyponatremia occurs as a result of

A

Incr TBW, either absolute or relative

36
Q

Mutation in X-linked Hypophosphatemia

A

PHEX

37
Q

___ is present in majority of cases of true hyponatremia

A

Appropriate or inappropriate increase in ADH

39
Q

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

A

Phosphate is trancellularly reabsorbed, Na can be either.

40
Q

3 functional segments of PT

A

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

42
Q

Severity of Cystinuria

A

Relatively benign, rarely causes kidney failure

44
Q

Hereditary Renal Glucosuria is caused by

A

mutation of SGLT2 Glucose transporter

44
Q

FGF-23 normally inhibits

A

Na-Pi cotransporter

46
Q

Classifications of PT dysfunction based on mechanism

A

Generalized vs Isolated Solute Transport Disorders

48
Q

Inheritance of Hereditary Renal Glucosuria

A

Autosomal recessive

49
Q

Water Deficit =

A

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

50
Q

Hyponatremia with Volume Overload is caused by

A

Decreased ECV: CHF, Kidney failure, Cirrhosis, Nephrotic

51
Q

Normal function of PHEX

A

Downregulate FGF23

53
Q

Parathyroid hormone regulates what in PT

A

Pi excretion

54
Q

Normal osmostic threshold for ADH release

A

280-290 mOsm/kg

56
Q

Fanconi Syndrome can be __, but is most commonly ___

A

Inherited, but most commonly acquired

58
Q

Susceptibility of PT to ischemia

A

High

59
Q

Osmotic threshold for thirst

A

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

60
Q

Patient with functional SGLT2 will have glucosuria if

A

[Glu] exceeds normal threshold

61
Q

How does pregnancy cause Nephrogenic DI

A

Placental synthesis of Vasopresinase

62
Q

Uosm in response to water deprivation in Primary Polydipsia

A

Increase

63
Q

Congenital Nephrogenic DI results from mutations in

A

V2 or Aquaporin 2

64
Q

Cwater =

A

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

65
Q

Normal Osmolarity Hyponatremia is due to

A

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
Q

3 inherited causes of Isolated Phosphate Reabsorption defect

A

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

68
Q

Acquired cause of Isolated Phosphate Reabsorption defect

A

Oncogenic Hypophosphatemic Osteomalacia

69
Q

Cosm =

A

Uosm/Posm x V

70
Q

Most common mutation related to phosphate reabsorption

A

X-Linked Hypo-P

71
Q

Why is PT highly susceptible to ischemia

A

ATP dependence, Polarized structure of cells

72
Q

K moving paracellularly is an example of

A

Simple diffusion requiring electrochemical gradient

73
Q

Mutation in FGF-23

A

AD Hypo-P Rickets

74
Q

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

A

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

76
Q

Most common electrolyte disorder

A

Hyponatremia

77
Q

Mitochondria in PT epithelial cells

A

Rich to provide sufficient energy for mass reabsorption

77
Q

Where is 100% of glucose reabsorbed

A

PT

78
Q

Mutation in AD Hypo-P Rickets

A

FGF-23

79
Q

How quickly does ADH insert new AQP-2 channels

A

within minutes

81
Q

Hyponatremia with normal volume status is caused by

A

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

82
Q

Which are more severe: Generalized or Isolated PT Dysfunctions

A

Generalized

83
Q

Hypoosmolar Hyponatremia is due to

A

Always due to impaired urinary dilution mechanisms

84
Q

“Generalized” PT dysfunction is usually due to

A

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

85
Q

25% of Na in PT is reabsorbed by what exchanger

A

Na-H

86
Q

mutation of SGLT2 Glucose transporter

A

Hereditary Renal Glucosuria is caused by

87
Q

What percent of Phosphorus is reabsorbed in PT

A

80%

88
Q

FGF23 regulates what in PT

A

Pi excretion

Renal (31 decks)

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