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
descending loop of henle characteristics
moderate permeability to water and ions | moderate rate/ moderate gradient epithelium
26
epithelial transport systems in descending loop of henle
almost no transporters | shows diffusion of NaCl, water, and urea
27
ascending loop of henle characteristics
moderate trans-cellular and paracellular permeability reabsorbs 25% of salt reabsorbs NaCl and Mg moderate rate/ moderate gradient epithelium
28
transport systems in ascending loop of henle
basal membrane: NaKATPase | apical membrane: NaK2Cl
29
distal tubule characteristics
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
30
transport systems in distal tubule
basal membrane: NaKATPase | apical membrane: Na-Cl co transporter
31
collecting tubule characteristics
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
32
principal cells transport mechanisms in collecting tubules
basal membrane: NaKATPase | apical membrane: ENac
33
intercalated cells transport mechanisms in collecting tubules
basal membrane: NaKATPase, Cl-bicarb exchanger | apical membrane: H ATPase, H,K ATPase
34
role of Na+ in the body
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
35
body sodium distribution
``` 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 ```
36
Na+ reabsorption in proximal tubule
apical Na+-glucose and Na+-H+ transporters | BM NaKATPase
37
Na+ reabsorption in thick ascending loop of Henle
apical Na+-K+-2CL- cotransporter | BM NaKATPase
38
Na+ reabsorption in the distal tubule
apical Na+-Cl- symporter | BM NaKATPase
39
Na+ reabsorption in the principal cells of collecting tubule
apical ENac | BM NaKATPase
40
regulators of Na+ transport at proximal tubules
extrarenal: angiotensin II renal: sympathetic nerve activity, glomerulotubular balance
41
regulators of Na+ transport at distal tubules
aldosterone | sympathetic nerve activity
42
regulators of Na+ transport at collecting tubule
atrial natriuretic peptide (ANP) | sympathetic nerve activity
43
potassium distribution in the body
``` 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
role of K+ in body
determines membrane resting potential and muscle and nerve excitability skeletal, cardiac and smooth muscle contractility metabolic processes protein and glycogen synthesis
45
renal handling of K+ in proximal tubule
most K+ reabsorbed by paracellular pathway secretion at luminal side minimal by K+ channels BM NKATPase
46
K+ reabsorption in thick ascending loop of Henle
most of K+ reabsorbed through N-K-2Cl transporter
47
K+ reabsorption in collecting tubule
principal cells: secrete K+ via Cl-K transporters and K-channels intercalated cells: secrete K+ via H, K ATPase and K-channels
48
factors stimulating K+ secretion
lumen: increased fluid flow, increased Na+, decreased Cl- capillary: increased aldosterone, increased ADH, increased plasma [K+]
49
most principal factors regulating K+ secretion
plasma [K+] aldosterone ADH smaller effect
50
chloride distribution in body
``` 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
role of Cl- in body
most important anion in ECF distribution follows Na+ determines volume of ECF with Na+
52
summary of Cl- regulation along the nephron
Cl- follows Na+ and its handling by the kidney is regulated by the agents that regulate Na+
53
calcium distribution in the body
5 mEq/L in plasma 50% ionized 40% protein bound 10% anion bound
54
role of Ca2+ in the body
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
Ca2+ reabsorption mechanisms in proximal tubule
majority reabsorbed by paracellular route (80%) apical Ca2+ channels BM Ca2+ ATPase, 3Na+-Ca2+ exchanger
56
Ca2+ reabsorption mechanisms in thick ascending loop of Henle
same as proximal tubule
57
Ca2+ reabsorption mechanisms in distal tubule
only transcellular apical Ca2+ channels BM Ca2+ ATPase, 3Na+-Ca2+ exchanger
58
phosphate distribution in the body
plasma levels 1.5-3 mEq/L 90% in bone 5% ionic 5% bound
59
role of phosphate in the body
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
phosphate handling by renal tubules
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
principle agents controlling calcium and phosphate homeostasis
``` parathyroid hormone (PTH) calcitriol (1,25-(OH)2-D3) ```
62
parathyroid hormone in calcium regulation
maintenance of [Ca2+] and phosphate concentration in the ECF | exerted at several levels
63
bone tissue in calcium regulation via PTH
mineral of bone is mobilized to maintain calcium and phosphate homeostasis PTH stimulates liberation of calcium from bone to increase calcemia
64
vitamin D metabolism in calcium regulation
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
kidneys in calcium regulation via PTH
PTH stimulates Ca2+ reabsorption in distal tubules and collecting ducts, reducing calcium excretion in the urine PTH also increases phosphate urinary excretion
66
main targets of calcitriol
intestinal mucosa bone kidney
67
intestine in calcium regulation
calcitriol increases calcium absorption in duodenum and proximal jejunum
68
bone in calcium regulation via calcitriol
calcitriol increases bone resorption | mobilizes calcium from bone and promotes formation and mineralization of new bone matrix to replace reabsorbed tissue
69
kidneys in calcium regulation via calcitriol
increases calcium and phosphate reabsorption in renal tubules inhibits synthesis of PTH
70
function of calcitonin
promotes bone formation
71
magnesium distribution in body
55% bone 44% ICF plasma 1% > 70% ionic, 30% bound
72
role of Mg2+ in body
essential cofactor for many enzyme reactions | important for regulation of ion channels and cell excitability
73
Mg2+ handling by renal tubules
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
mechanism of glucose reabsorption in proximal tubule
SGLT2 in apical membrane 1 na+:1 glucose BM GLUT2 and NaKATPase to create Na gradient
75
what is the tubular maximum (Tm)
maximum amount of any substance that can be reabsorbed
76
Tm for glucose
375 mg/min | glucose excreted in urine when this load is exceeded
77
renal plasma threshold for glucose
180 mg/dL
78
mechanisms of AA reabsorption in proximal tubule
Na+-AA symport driven by BM NaKATPase
79
urea balance in the body
liver metabolizes protein into urea plasma BUN 9-18 mg/dL 40% reabsorbed in kidneys 60% excreted
80
countercurrent concentration of urea
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
regulation of urea handling under physiological conditions
increased ADH and increased water transport upregulate urea transporters UT1 and UT1 which increases urea reabsorption at collecting tubules
82
regulation of urea handling under pathological conditions
in pts with renal failure GFR is reduced and urea accumulates in plasma at high levels increased BUN
83
uric acid balance in the body
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
uric acid handling by kidney
8-12% excreted net reabsorption usually prevails (first and last segments of proximal tubules) secreted in middle section of proximal tubule
85
water reabsorption in the nephron
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
what is the glomerulotubular balance
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
how do you determine renal tubular function
measure ability to reabsorb or secrete solutes
88
important of renal tubular function determination
diagnosis of renal tubular disease | progression of alteration of the renal tubule
89
fractional excretion of a solute
FEs =[ Us/Ps]/ [Ucr/Pcr] | commonly Na is used (normal 1-3%)
90
what measure is an indicator of both glomerular and tubular function
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
BUN/Cr values
normal = 15 BUN/Cr > 15 glomeruli more affected BUN/Cr < 15 tubules more affected
92
diuretics
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
what 4 factors does diuretic effect depend on?
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)