Exam 8 - Tubular Reabsorption & Secretion Flashcards

1
Q

Filtration rate

A

GFR x Plasma [ ]

Normal GFR = 180 L/day

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2
Q

100% filtered nutrients

A
  • Glucose
  • Bicarb
  • Na
  • Cl (99%)

Others:

  • K (88%)
  • Urea (50%)
  • Creatinine (0%)
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3
Q

Primary active transport mechanisms in reabsorption

A
  • Na/K ATPase (drives O2 consumption)
  • H ATPase
  • H-K ATPase
  • Ca ATPase
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4
Q

Co-transport mechanisms in reabsorption

A
  • Na/glucose
  • Na/amino acids
  • both concentrate in the body…move into body with Na
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5
Q

Counter transport mechanisms in reabsorption

A
  • Na/H

- move H into lumen for excretion…opposite Na

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6
Q

Pinocytosis

A
  • movement of proteins back into body

- protein in urine is bad

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7
Q

Passive mechanisms in reabsorption

A
  • H20

- bulk flow

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8
Q

Na/K ATPase

A
  • Na into interstitial space and K into tubular cells
  • on basolateral side
  • creates -70mV potential in tubular cells
    • drives Na into cell via electrical and [ ] gradient
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9
Q

Na [ ] gradient

A
  • on brush border side (20x rate increase)
  • [ ] and electrical gradients drive Na from lumen into tubular cells
  • Na also pushed in via other co-transporters/counter-transport
  • Na quickly moves with H20 from interstitial into capillary
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10
Q

Glucose reabsorption

A

Luminal:

  • Co-transport with Na
  • SGLT2…90%…early part
  • SGLT1…10%…later part

Basolateral:

  • passively down [ ] gradient
  • GLUT2…early / GLUT1…later
  • Bulk flow moves from interstitial into capillary
  • cell membrane not permeable to glucose
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11
Q

Amino acid reabsorption

A
  • co-transport pump w/ Na on lumen side
  • diffuse out of cell on basolateral side following [ ] gradient
  • moves into capillary via bulk flow
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12
Q

H secretion

A
  • Don’t want to absorb / control pH balance
  • Na/H counter transport on brush border
  • H gets trapped in lumen
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13
Q

Max solute transport

A
  • depends on type of transport
  • Max tubular reabsorption
  • Max secretion
  • Gradient-time transport (Na…although mainly Na/K ATPase)
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14
Q

Max reabsorption of glucose

A
  • in mg/min
  • carrier proteins are saturated
  • glucose filtered load = 125 mg/min
  • glucose Tmax = 375 mg/min
  • at 200 mg/dl…glucose seen in urine
  • why do we see glucose in urine at 200?
  • so many nephrons…all are different…avg is 375
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15
Q

Tmax of plasma proteins

A
  • 30 mg/dl

- not normally that high

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16
Q

Absorption

A

Filtered > excretion

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17
Q

Secretion

A

Filtered < excretion

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18
Q

Creatinine Tmax

A
  • secretion

- 16 mg/dl

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19
Q

PAH Tmax

A
  • 80 mg/min

- secreted

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20
Q

Gradient time transport max

A

Depends on:

  • electrochemical gradient
  • membrane permeability
  • time in tubule (longer time…more transport)
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21
Q

Na Tmax

A
  • not shown… high Na/K pump capacity
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22
Q

Na leak back into lumen

A

Caused by:

  • through tight junctions
  • interstitial [ ] of Na
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23
Q

Na reabsorption in proximal tubule

A
  • [plasma Na] up…[tubule Na] up… reabsorption up
  • drop in tubular flow rate also increase Na absorption
    • MAP down…GFR down…tube flow down…reabsorption up…H2O up… MAP up
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24
Q

Na reabsorption in distal tubule

A
  • can show a Tmax
  • minimal back leak…tighter junctions
  • aldosterone increases Tmax for Na in distal
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25
Q

What replaces Na as H2O driving force in later parts

A

Urea

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26
Q

H2O absorption in proximal tubule

A
  • highly permeable
  • rapid movement…so solute gradient minimal
  • solvent drag: H2O carries solute with it due to high permeability
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27
Q

H2O in loop of Henle (ascending) / early distal

A
  • low permeability

- little movement even though large osmotic gradient

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28
Q

H2O in distal / collecting tubules and ducts

A
  • variable permeability…depends on ADH

- no solvent drag…just water can move here

29
Q

Passive Cl reabsorption

A

Driven by Na reabsorption:

  • more negative lumen…pushes Cl into cell
  • more H2O in…makes lumen [Cl] high…drives Cl into cell
  • Cl also cotransport with Na in lumen side
30
Q

Passive Urea reabsorption

A
  • H2O into cells makes lumen [urea] high
  • drives urea into cell
  • happens in collecting duct
  • only 50% reabsorption
31
Q

% reabsorption in proximal tubule

A
  • 65% of Na and H2O
  • little less foe Cl…it follows Na and H2O
  • can be increased or decreased in later parts
32
Q

Proximal tubule structure

A
  • lots of mitochondria for active transport
  • high SA brush border
  • transport proteins for co/counter (glucose, AA / H)
  • lots of Na/K ATPase in basolateral border
  • isosmotic…Na/H20 absorbed at same rate
33
Q

Early proximal tubule

A
  • majority of reabsorption
  • co transport of glucose and amino acids
  • Na carries glucose, bicarb, organics…leaves Cl
    • increase [Cl] here… 105 to 140
34
Q

Late proximal tubule

A
  • Na drives Cl reabsorption
  • high [Cl] favors diffusion
    • small amount through Cl specific channels
35
Q

Proximal tubule volume concentrations

A
  • stays isosmotic due to Na/H2O reabsorption at same rate
  • creatinine/urea not secreted yet…but [ ] up due to H2O down
    • total amount does not change
  • Na/Cl/bicarb/glucose/AA amount all go down
36
Q

Secretion in proximal tubule

A

Metabolites:
-bile salts / oxalate / irate / catecholamines
Toxins/Drugs:
- penicillin / salicylates

  • Also PAH…90% removed…used to determine RBF
37
Q

Juxtoglomerular nephrons

A
  • [ ] urine
38
Q

Thin descending loop

A
  • thin epi / no brush border / few mito / minimal metabolic
  • reabsorption of H2O…high permeable
  • moderately permeable to solute (H2O carries… no active)
  • 20% of H2O reabsorption in loop
    • Ascending part IMPERMEABLE to water
39
Q

Thick ascending loop

A
  • thick epi / lots of mito / high metabolic
  • reabsorption Na / Cl / K / Ca / bicarb / Mg….25% of load
  • dilute here…no water reabsorption
  • Hyposmotic here… 90% Na in…only 85% water in
40
Q

Na reabsorption in thick ascending

A
  • driven by Na/K ATPase in basolateral border (Na out/K in)
  • 1 Na-2 Cl-1 K co transport into cell from lumen
    • primary mover of Na at this level
    • K moves against gradient
    • Cl and K diffuse out into interstitial via specific channels
  • Na/H counter transport here as well
41
Q

Loop diuretics

A
  • affect thick ascending loop
  • block 1-2-1
  • Furosemide / Ethacrynic acid / Bumetanide
  • less Na reabsorption… less water in… less K in
    • loss of K a problem here
42
Q

Paracellular reabsorption in thick ascending

A
  • Na/K/Mg/Ca
  • driven by electrochemical gradient through tight junctions
  • 1-2-1 carrier keeps ISO electric but K leaks back into lumen
    • cause +8mV in lumen…pushes ions through out of lumen
43
Q

Early distal tubule

A
  • macula dense first part…feedback for GFR/blood flow
    • macula dense only in juxtaglomerular nephron
  • second part highly convoluted
    • solute reabsorbed…H2O NO (diluting segment)
  • 5% of Na/Cl here
  • Na/K in basolateral border
  • Na/Cl co transport into cell
  • Cl diffuse into interstitial via specific channels
  • Thiazide diuretics block Na/Cl co transport
    • reduces H2O reabsorption in later parts
    • no effect on K [ ]
44
Q

Late distal / collecting tubule

A
  • impermeable to urea
  • Na reabsorption / K secretion controlled via aldosterone
  • secrete H ions against 1000:1 gradient
    • proximal only 4-10:1
  • H2O permeability controlled by ADH aka vasopressin
45
Q

Principal cells

A
  • in late distal / cortical collecting tubule
  • reabsorb Na/H2O
  • secrete K
  • Na/K ATPase on basolateral drives activity
  • Na in from lumen via gradient
  • K out into lumen via gradient
46
Q

Intercalated cells

A
  • reabsorb K
  • secrete H
    • H-ATPase on lumen side
    • H from carbonic anhydrase rxn
    • bicarb out into capillary via Cl co-transport on basolateral side
    • Cl out into lumen
    • CO2 in and out freely on basolateral side
47
Q

K sparing diuretics - Aldosterone antagonists

A
  • competitive at receptor site
  • block Na/H2O reabsorption and K secretion
  • Spironolactone
  • Eplerenone
48
Q

K sparing diuretics - Na channel blockers

A
  • block entry on Na on lumen side
  • reduces Na movement via Na/K ATPase
    • which reduces K secretion
  • Amiloride
  • Triamterene
49
Q

Collecting duct

A
  • 10% of H2O/Na
  • determines final [ ] of urine
  • few mito
  • H2O permeability controlled via ADH
  • Urea main driver now…via Urea reabsorption
  • secretes H ions like collecting tubule
50
Q

Inulin

A
  • neither secreted or reabsorbed
  • provides indicator of H2O reabsorption
  • similar to creatinine except creatinine slightly secreted

If inulin [ ] = 3…1/3 of water in tubule…2/3 reabsorbed

51
Q

Regulating tubular reabsorption

A
  • glomerulotubular balance
  • peritubular capillary and interstitial forces
  • arterial BP
  • hormones
  • sympathetic nervous effect (not big effect) (Na absorption up)
  • some controlled independently
52
Q

Glomerulotubular balance

A
  • increase in reabsorption if increase in tubular load
  • If GFR up to 150 from 125…proximal will still take 65% of total
  • maintains Na and volume homeostasis
  • keep normal flows to distal tubule even if big change in MAP
53
Q

Peritubular capillary and interstitial forces

A
  • Net reabsorption across length of capillary
  • IN (32o+6) - OUT (13+15o) = 10 IN
  • Normal rate of reabsorption = 124 ml/min
  • interstitial #’s only change if disease
  • reabsorption coefficient = 12.4 mls/min/mmHg
54
Q

Peritubular hydrostatic pressure increase…

A
  • reabsorption down
    Caused by:
  • MAP up
  • resistance of arterioles down
55
Q

Peritubular oncotic pressure increase…

A
  • reabsorption increases
    Caused by:
  • plasma protein up
  • Filtration fraction up

Fraction = GFR / RPF

56
Q

Reabsorption coefficient

A
  • affected by permeability and surface area
    • directly related
  • if coefficient up…reabsorption up
  • only changes in diseased states
57
Q

Arterial pressure control

A
  • Increase MAP…slightly less reabsorption of Na/H2O
  • small increase in cap hydrostatic / increase in interstitial hydrostatic / increase backflow into lumen
    THEN….
  • angio II decreases… less Na reabsorption.. less aldosterone …less Na reabsorption
58
Q

Aldosterone

A
  • collecting duct/tubule
  • increase NaCl/H2O absorption
  • increase K secretion
  • regulator of K
    Stimulated by:
  • increase K
  • increase angio II
Addison's = absence 
Conn's = excess
59
Q

Angio II

A
  • Proximal / Thick / distal / collecting
  • increase NaCl / H2O reabsorption
  • increase K secretion
  • most powerful
  • stimulated by low BP/volume
  • affects transport on both borders
  • very active in proximal
60
Q

ADH / vasopressin

A
  • distal / collecting
  • increase H2O absorption
  • made in hypothalamus … released in post pit
  • binds with V2 receptors on basolateral
  • stimulates H2O channels to open on lumen side
  • absence causes diabetes insipidus…19L urine
61
Q

Atrial natriuretic peptide

A
  • distal / collecting

- decrease NaCl reabsorption

62
Q

PTH

A
  • proximal / thick / distal
  • increase Ca reabsorption
  • decrease PO4 reabsorption
63
Q

Clearance formula

A

Cz x [Pz] = [Uz] x V

Clearance/Volume = ml/min
[ ] = mg/ml

64
Q

Urine excretion rate

A

V x Uz

65
Q

Filtration rate

A

GFR x Pz

66
Q

Measure of GFR

A
  • Inulin…freely filtered…neither secreted/absorbed
  • We use creatinine…close
    • excreted slightly more than filtered
    • plasma [ ] estimation overestimates…so we cancel
  • 4x levels of creatinine in blood = 1/4 of normal GFR
  • creatinine normal = <1.5
67
Q

PAH in renal plasma flow

A
  • 90% cleared

RPF = PAH clearence / 0.9

RBF = RPF / (1-Hct) or 22% of CO

68
Q

Absorption formula

A

Filtered - excretion

GFR x Pz) - (V x Uz

69
Q

Secretion formula

A

Excretion - Filtered

Uz x V) - (GFR x Pz