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GIR Test 2 > B5.037 Renal Physiology II: Tubular Reabsorption > Flashcards

B5.037 Renal Physiology II: Tubular Reabsorption Flashcards

1
Q

3 sections of the renal tubule

A

proximal tubule
Henle’s loop
distal convoluted tubule

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2
Q

proximal tubule cells

A

cuboidal, columnar cells
numerous microvilli on apical membrace that expand surface area of luminal membrane (“brush border”)
opposite side of cell has many infoldings resting on the basement membrane
many mitochondria present
tight junctions between cells on luminal side
gap junctions for passage of small molecules and ions

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3
Q

loop of Henle cells

A

descending: flat, no brush border, few microvilli, few mitochondria
ascending, thick section: cuboidal, columnar cells without brush border

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4
Q

distal convoluted tubule cells

A

cuboidal, columnar cells without brush border

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5
Q

collecting duct cells

A

principal cells- 2/3 of cells, abundant invaginations of the basolateral membrane and few mitochondrial
intercalated cells- many mitochondria

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6
Q

2 pathways across renal tubular epithelium

A

transcellular through cell

paracellular between cells, across the zonula occludens

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7
Q

transcellular pathways

A

apical membrane has channels and carriers that allow entrance of water and solutes into cell or that secrete solutes into tubular lumen
basolateral membrane has a variety of transporters, Na+K+ATPase pump exlusively located in this domain to create electrochemical gradient

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8
Q

paracellular pathway

A

tight junctions in proximal tubule leaky and allow passive diffusion of water and ions between the tubular lumen and intercellular space

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9
Q

structure of the tight junctions between renal epithelial cells

A

composed of occluding and claudin

anchored into cells with actin filaments and cytoskeleton

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10
Q

properties of renal epithelium that change along the nephron

A

surface area
permeability to ions and solutes
permeability to water

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11
Q

examples of transport mechanisms across epithelia

A

simple diffusion
passive transport (channels)
primary active transport
secondary active transport

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12
Q

passive diffusion

A

flow from high to low concentration

no energy input

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13
Q

uniports

A

transfer only one class of solute across a membrane

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14
Q

primary active transport

A

use energy from ATP to transport solutes across a gradient

Na+K+ATPase on basolateral membrane

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15
Q

secondary active transport

A 
not directly coupled to ATP hydrolysis
function in the direction imposed by the chemical/electrochemical gradient
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16
Q

normal extracellular concentrations

A

Na+ 145 mM
K+ 5 mM
Cl- 116 mM
Ca2+ 1 mM

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17
Q

normal intracellular concentrations

A

Na+ 5 mM
K+ 145 mM
Cl- 20 mM
Ca2+ 1mM

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18
Q

common channels in renal epithelial cells

A

Na+
K+
Cl-
Ca2+

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19
Q

common primary active transport systems in renal epithelium

A

Na+K+ ATPase
Ca2+ATPase
H+ ATPase

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20
Q

common secondary active transport systems in renal epithelium

A

Na+ H+ antiporter
Na+ Ca2+ antiporter
Na+ K+ 2Cl- transporter
SGLT2

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21
Q

basic ion transport systems of the renal tubule

A

Na+K+ATPase located exclusively on BM
K+ accumulated intracellularly, creating electrical gradient
Na+ concentration lower in cell than in ECM, provides a driving force for Na+ entry into cell from lumen and movement of other solutes
Na+ followed by Cl- > gets salt into bloodstream

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22
Q

proximal tubule transport characteristics

A

high trans cellular water and salt permeability
paracellular high ion and water conduction
absorbs 60-70% of GFR including salt and water
absorbs 100% of glucose and AAs
secreted uric acid, drugs
high reabsorption rate/ low gradient epithelium

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23
Q

basal transport systems in proximal tubules

A

NaKATPase
Na-bicarb transporter
Ca and HPO4 transporter

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24
Q

apical transport systems in proximal tubules

A

Na channels
Na-H antiporter
Na-glucose
Na-AAs

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25
Q

descending loop of henle characteristics

A

moderate permeability to water and ions

moderate rate/ moderate gradient epithelium

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26
Q

epithelial transport systems in descending loop of henle

A

almost no transporters

shows diffusion of NaCl, water, and urea

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27
Q

ascending loop of henle characteristics

A

moderate trans-cellular and paracellular permeability
reabsorbs 25% of salt
reabsorbs NaCl and Mg
moderate rate/ moderate gradient epithelium

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28
Q

transport systems in ascending loop of henle

A

basal membrane: NaKATPase

apical membrane: NaK2Cl

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29
Q

distal tubule characteristics

A

low transcellular and paracellular permeability to water and ions
reabsorption of NaCl
reabsorption and secretion of K+
variable NaCl reabsorption depending on aldosterone
variable water absorption depending on ADH
low rate/ high gradient epithelium

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30
Q

transport systems in distal tubule

A

basal membrane: NaKATPase

apical membrane: Na-Cl co transporter

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31
Q

collecting tubule characteristics

A

low transcellular and paracellular permeability to water and ions
reabsorption of NaCl and secretion of K+
secretion of H+ and HCO3
variable NaCl reabsorption depending on aldosterone
variable water absorption depending on ADH
low rate/ high gradient epithelium

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32
Q

principal cells transport mechanisms in collecting tubules

A

basal membrane: NaKATPase

apical membrane: ENac

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33
Q

intercalated cells transport mechanisms in collecting tubules

A

basal membrane: NaKATPase, Cl-bicarb exchanger

apical membrane: H ATPase, H,K ATPase

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34
Q

role of Na+ in the body

A

main electrolyte of ECF
most important cation in determination of ECF osmolarity
determines volume of ECF
controls fluid movement between body compartments
important for reabsorption/secretion of water and other solutes in and out of cells

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35
Q

body sodium distribution

A 
100-200 mmole/day intake
2300 mmole in ECF (86%)
370 mmole in ICF (14%)
kidney excretes 100-150 mmole/day
intestine excretes 5 mmole/day
skin excretes 15 mmole/day
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36
Q

Na+ reabsorption in proximal tubule

A

apical Na+-glucose and Na+-H+ transporters

BM NaKATPase

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37
Q

Na+ reabsorption in thick ascending loop of Henle

A

apical Na+-K+-2CL- cotransporter

BM NaKATPase

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38
Q

Na+ reabsorption in the distal tubule

A

apical Na+-Cl- symporter

BM NaKATPase

39
Q

Na+ reabsorption in the principal cells of collecting tubule

A

apical ENac

BM NaKATPase

40
Q

regulators of Na+ transport at proximal tubules

A

extrarenal: angiotensin II
renal: sympathetic nerve activity, glomerulotubular balance

41
Q

regulators of Na+ transport at distal tubules

A

aldosterone

sympathetic nerve activity

42
Q

regulators of Na+ transport at collecting tubule

A

atrial natriuretic peptide (ANP)

sympathetic nerve activity

43
Q

potassium distribution in the body

A 
100 mEq/day intake
70 mEq in ECM (2%)
3500 mEq in ICF (98%)
kidney excretes 90-95 mEq/day
intestine excretes 5-10 mEq/day
44
Q

role of K+ in body

A

determines membrane resting potential and muscle and nerve excitability
skeletal, cardiac and smooth muscle contractility
metabolic processes
protein and glycogen synthesis

45
Q

renal handling of K+ in proximal tubule

A

most K+ reabsorbed by paracellular pathway
secretion at luminal side minimal by K+ channels
BM NKATPase

46
Q

K+ reabsorption in thick ascending loop of Henle

A

most of K+ reabsorbed through N-K-2Cl transporter

47
Q

K+ reabsorption in collecting tubule

A

principal cells: secrete K+ via Cl-K transporters and K-channels
intercalated cells: secrete K+ via H, K ATPase and K-channels

48
Q

factors stimulating K+ secretion

A

lumen: increased fluid flow, increased Na+, decreased Cl-
capillary: increased aldosterone, increased ADH, increased plasma [K+]

49
Q

most principal factors regulating K+ secretion

A

plasma [K+]
aldosterone
ADH smaller effect

50
Q

chloride distribution in body

A 
intake 10-200 mmole/day
2000 mmole in ECF
200 mmole in ICF
kidney excretes 100-200 mmole/day
intestine excretes 5 mmole/day
skin excretes 15 mmole/day
51
Q

role of Cl- in body

A

most important anion in ECF
distribution follows Na+
determines volume of ECF with Na+

52
Q

summary of Cl- regulation along the nephron

A

Cl- follows Na+ and its handling by the kidney is regulated by the agents that regulate Na+

53
Q

calcium distribution in the body

A

5 mEq/L in plasma
50% ionized
40% protein bound
10% anion bound

54
Q

role of Ca2+ in the body

A

forms mineral component of bone
as free ion is important for nerve and muscle excitability
cell secretory processes (hormones, neurotransmitters)
regulation of many enzymes
important intracellular second messenger in cells
blood coagulation

55
Q

Ca2+ reabsorption mechanisms in proximal tubule

A

majority reabsorbed by paracellular route (80%)
apical Ca2+ channels
BM Ca2+ ATPase, 3Na+-Ca2+ exchanger

56
Q

Ca2+ reabsorption mechanisms in thick ascending loop of Henle

A

same as proximal tubule

57
Q

Ca2+ reabsorption mechanisms in distal tubule

A

only transcellular
apical Ca2+ channels
BM Ca2+ ATPase, 3Na+-Ca2+ exchanger

58
Q

phosphate distribution in the body

A

plasma levels 1.5-3 mEq/L
90% in bone
5% ionic
5% bound

59
Q

role of phosphate in the body

A

form mineral component of the bone
important component of nucleic acids and many organic molecules
forms part of energy molecules
regulator of many intracellular pathways

60
Q

phosphate handling by renal tubules

A

proximal tubules reabsorb about 85% of phosphate filtered
5% in thick ascending lib and 10% ecreted
apical 2Na+-HPO4 cotransporter
BM phosphate-anion exchanger

61
Q

principle agents controlling calcium and phosphate homeostasis

A 
parathyroid hormone (PTH)
calcitriol (1,25-(OH)2-D3)
62
Q

parathyroid hormone in calcium regulation

A

maintenance of [Ca2+] and phosphate concentration in the ECF

exerted at several levels

63
Q

bone tissue in calcium regulation via PTH

A

mineral of bone is mobilized to maintain calcium and phosphate homeostasis
PTH stimulates liberation of calcium from bone to increase calcemia

64
Q

vitamin D metabolism in calcium regulation

A

PTH stimulates production of calcitriol in cells of renal proximal tubules
this is an active metabolite of vitamin D
increases intestinal absorption of calcium and contributes to raise calcium concentration in ECF

65
Q

kidneys in calcium regulation via PTH

A

PTH stimulates Ca2+ reabsorption in distal tubules and collecting ducts, reducing calcium excretion in the urine
PTH also increases phosphate urinary excretion

66
Q

main targets of calcitriol

A

intestinal mucosa
bone
kidney

67
Q

intestine in calcium regulation

A

calcitriol increases calcium absorption in duodenum and proximal jejunum

68
Q

bone in calcium regulation via calcitriol

A

calcitriol increases bone resorption

mobilizes calcium from bone and promotes formation and mineralization of new bone matrix to replace reabsorbed tissue

69
Q

kidneys in calcium regulation via calcitriol

A

increases calcium and phosphate reabsorption in renal tubules
inhibits synthesis of PTH

70
Q

function of calcitonin

A

promotes bone formation

71
Q

magnesium distribution in body

A

55% bone
44% ICF
plasma 1% > 70% ionic, 30% bound

72
Q

role of Mg2+ in body

A

essential cofactor for many enzyme reactions

important for regulation of ion channels and cell excitability

73
Q

Mg2+ handling by renal tubules

A

25% passively reabsorbed in proximal tubule through paracellular pathway
60% reabsorbed in thick ascending loop via apical Mg2+ channels and BM Mg-ATPase and Na-Mg exchangers

74
Q

mechanism of glucose reabsorption in proximal tubule

A

SGLT2 in apical membrane
1 na+:1 glucose
BM GLUT2 and NaKATPase to create Na gradient

75
Q

what is the tubular maximum (Tm)

A

maximum amount of any substance that can be reabsorbed

76
Q

Tm for glucose

A

375 mg/min

glucose excreted in urine when this load is exceeded

77
Q

renal plasma threshold for glucose

78
Q

mechanisms of AA reabsorption in proximal tubule

A

Na+-AA symport driven by BM NaKATPase

79
Q

urea balance in the body

A

liver metabolizes protein into urea
plasma BUN 9-18 mg/dL
40% reabsorbed in kidneys
60% excreted

80
Q

countercurrent concentration of urea

A

urea secreted in loop of Henle
urea reabsorbed with water in collecting duct into vasa recta
within vasa recta, urea is trapped and recycled

81
Q

regulation of urea handling under physiological conditions

A

increased ADH and increased water transport upregulate urea transporters UT1 and UT1 which increases urea reabsorption at collecting tubules

82
Q

regulation of urea handling under pathological conditions

A

in pts with renal failure GFR is reduced and urea accumulates in plasma at high levels
increased BUN

83
Q

uric acid balance in the body

A

produced from metabolism of adenosine and guanine in the liver
breaks down to urate and H+
plasma conc 4-6 mg/dL
reabsorbed in first and last segments of proximal tubule
secreted in middle segment of proximal tubule

84
Q

uric acid handling by kidney

A

8-12% excreted
net reabsorption usually prevails (first and last segments of proximal tubules)
secreted in middle section of proximal tubule

85
Q

water reabsorption in the nephron

A

proximal tubules: movement driven by Starling’s forces (difference in hydrostatic and oncotic pressures)
collecting ducts: reabsorption via transcellular pathway through aquaporins regulated by ADH

86
Q

what is the glomerulotubular balance

A

sodium and water reabsorption parallels changes in the GFR and amount of filtered Na+
proportion of Na+ and water reabsorbed in proximal tubule is always the same regardless of total volume of filtrate

87
Q

how do you determine renal tubular function

A

measure ability to reabsorb or secrete solutes

88
Q

important of renal tubular function determination

A

diagnosis of renal tubular disease

progression of alteration of the renal tubule

89
Q

fractional excretion of a solute

A

FEs =[ Us/Ps]/ [Ucr/Pcr]

commonly Na is used (normal 1-3%)

90
Q

what measure is an indicator of both glomerular and tubular function

A

BUN/Cr
creatinine is mainly filtered so it provides info on glomerular function
Urea is filtered and reabsorbed so it gives an estimate of GFR and tubular function

91
Q

BUN/Cr values

A

normal = 15
BUN/Cr > 15 glomeruli more affected
BUN/Cr < 15 tubules more affected

92
Q

diuretics

A

compounds that cause diuresis
inhibit Na+ reabsorption at various sites of the nephron
effect not limited to Na+ and other ions are also secreted
used to treat HTN and edematous disorders

93
Q

what 4 factors does diuretic effect depend on?

A
  1. site of action (loop most powerful)
  2. response of other nephron segments (compensatory reabsorption distally from site of action)
  3. adequate delivery to site of action (depends on GFR)
  4. volume of ECF (if low, GFR and Na+ load will be low)

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