Exam 8 - Tubular Reabsorption & Secretion Flashcards
Filtration rate
GFR x Plasma [ ]
Normal GFR = 180 L/day
100% filtered nutrients
- Glucose
- Bicarb
- Na
- Cl (99%)
Others:
- K (88%)
- Urea (50%)
- Creatinine (0%)
Primary active transport mechanisms in reabsorption
- Na/K ATPase (drives O2 consumption)
- H ATPase
- H-K ATPase
- Ca ATPase
Co-transport mechanisms in reabsorption
- Na/glucose
- Na/amino acids
- both concentrate in the body…move into body with Na
Counter transport mechanisms in reabsorption
- Na/H
- move H into lumen for excretion…opposite Na
Pinocytosis
- movement of proteins back into body
- protein in urine is bad
Passive mechanisms in reabsorption
- H20
- bulk flow
Na/K ATPase
- 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
Na [ ] gradient
- 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
Glucose reabsorption
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
Amino acid reabsorption
- co-transport pump w/ Na on lumen side
- diffuse out of cell on basolateral side following [ ] gradient
- moves into capillary via bulk flow
H secretion
- Don’t want to absorb / control pH balance
- Na/H counter transport on brush border
- H gets trapped in lumen
Max solute transport
- depends on type of transport
- Max tubular reabsorption
- Max secretion
- Gradient-time transport (Na…although mainly Na/K ATPase)
Max reabsorption of glucose
- 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
Tmax of plasma proteins
- 30 mg/dl
- not normally that high
Absorption
Filtered > excretion
Secretion
Filtered < excretion
Creatinine Tmax
- secretion
- 16 mg/dl
PAH Tmax
- 80 mg/min
- secreted
Gradient time transport max
Depends on:
- electrochemical gradient
- membrane permeability
- time in tubule (longer time…more transport)
Na Tmax
- not shown… high Na/K pump capacity
Na leak back into lumen
Caused by:
- through tight junctions
- interstitial [ ] of Na
Na reabsorption in proximal tubule
- [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
Na reabsorption in distal tubule
- can show a Tmax
- minimal back leak…tighter junctions
- aldosterone increases Tmax for Na in distal
What replaces Na as H2O driving force in later parts
Urea
H2O absorption in proximal tubule
- highly permeable
- rapid movement…so solute gradient minimal
- solvent drag: H2O carries solute with it due to high permeability
H2O in loop of Henle (ascending) / early distal
- low permeability
- little movement even though large osmotic gradient
H2O in distal / collecting tubules and ducts
- variable permeability…depends on ADH
- no solvent drag…just water can move here
Passive Cl reabsorption
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
Passive Urea reabsorption
- H2O into cells makes lumen [urea] high
- drives urea into cell
- happens in collecting duct
- only 50% reabsorption
% reabsorption in proximal tubule
- 65% of Na and H2O
- little less foe Cl…it follows Na and H2O
- can be increased or decreased in later parts
Proximal tubule structure
- 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
Early proximal tubule
- majority of reabsorption
- co transport of glucose and amino acids
- Na carries glucose, bicarb, organics…leaves Cl
- increase [Cl] here… 105 to 140
Late proximal tubule
- Na drives Cl reabsorption
- high [Cl] favors diffusion
- small amount through Cl specific channels
Proximal tubule volume concentrations
- 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
Secretion in proximal tubule
Metabolites:
-bile salts / oxalate / irate / catecholamines
Toxins/Drugs:
- penicillin / salicylates
- Also PAH…90% removed…used to determine RBF
Juxtoglomerular nephrons
- [ ] urine
Thin descending loop
- 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
Thick ascending loop
- 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
Na reabsorption in thick ascending
- 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
Loop diuretics
- 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
Paracellular reabsorption in thick ascending
- 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
Early distal tubule
- 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 [ ]
Late distal / collecting tubule
- 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
Principal cells
- 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
Intercalated cells
- 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
K sparing diuretics - Aldosterone antagonists
- competitive at receptor site
- block Na/H2O reabsorption and K secretion
- Spironolactone
- Eplerenone
K sparing diuretics - Na channel blockers
- block entry on Na on lumen side
- reduces Na movement via Na/K ATPase
- which reduces K secretion
- Amiloride
- Triamterene
Collecting duct
- 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
Inulin
- 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
Regulating tubular reabsorption
- glomerulotubular balance
- peritubular capillary and interstitial forces
- arterial BP
- hormones
- sympathetic nervous effect (not big effect) (Na absorption up)
- some controlled independently
Glomerulotubular balance
- 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
Peritubular capillary and interstitial forces
- 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
Peritubular hydrostatic pressure increase…
- reabsorption down
Caused by: - MAP up
- resistance of arterioles down
Peritubular oncotic pressure increase…
- reabsorption increases
Caused by: - plasma protein up
- Filtration fraction up
Fraction = GFR / RPF
Reabsorption coefficient
- affected by permeability and surface area
- directly related
- if coefficient up…reabsorption up
- only changes in diseased states
Arterial pressure control
- 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
Aldosterone
- 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
Angio II
- 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
ADH / vasopressin
- 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
Atrial natriuretic peptide
- distal / collecting
- decrease NaCl reabsorption
PTH
- proximal / thick / distal
- increase Ca reabsorption
- decrease PO4 reabsorption
Clearance formula
Cz x [Pz] = [Uz] x V
Clearance/Volume = ml/min
[ ] = mg/ml
Urine excretion rate
V x Uz
Filtration rate
GFR x Pz
Measure of GFR
- 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
PAH in renal plasma flow
- 90% cleared
RPF = PAH clearence / 0.9
RBF = RPF / (1-Hct) or 22% of CO
Absorption formula
Filtered - excretion
GFR x Pz) - (V x Uz
Secretion formula
Excretion - Filtered
Uz x V) - (GFR x Pz
