Lecture 3- Renal Transport Flashcards
How much fluid does the kidney filter per day?
180 L
> 99% of filtered
water, Na, Cl, and HCO3
100% of filtered
glucose are reabsorbed
Facilitated diffusion
- passive movement of solute
- i.e. glucose transport
Coupled transport
- movement of two solutes. couples
- cotransport: solutes move in same direction (Na/glucose cotransporter)
- antiport: solutesmove in opposite direction (Na/H antiporter)
active transport
movement of solute up a concentration gradient
- require input of energy
- Na/K ATPase
endocytosis
invagination of region of plasma membrane
- captures material in extracellular space
- internalize material w/in endosome then traffic to lysosome for degradation
transcellular
through apical surface; through cell into basolateral surface
paracellular
between cells via junction (i.e. water and solutes – solvent drag)
Transport in the proximal tubule
67% of Na, Cl, and water is reabsorbed into PT
-reabsorption is iso-osmotic since reabsorption of water follows uptake of solutes
-primary driving force for transport = Na/K ATPase
(low cytoplasmic Na concentration in tubular cells)
First Half of the Proximal Tubule
Na+ Reabsorption Coupled to HCO3- Reabsorption
- Na+ crosses apical membrane via Na+/H+ antiporter
- Lumenal H+ facilitates HCO3- uptake
- Cytoplasmic CO2 converted to H+ and HCO3- by carbonic annhydrase (CA)
- Cytoplasmic HCO3- crosses basolateral membrane via Cl-/HCO3- exchanger and Na+/HCO3- cotransporter
- CA inhibitors at as diuretics
First Half of the Proximal Tubule
Na+ Reabsorption Coupled to Sugar and Amino Acid
- Low cytoplasmic Na+ drives uptake of sugars and amino acids across apical membrane via Na+-coupled cotransporters
- Sugars and amino acids cross the basolateral membrance via passive transport
Cystinuria
caused by loss of a Na-coupled amino acid transporter (characterized by kidney stones)
Second Half of the Proximal Tubule
- Na+ moves across apical membrane via Na+/H+ antiporter
- H+ re-enter from lumen by combining with anions (i.e. formate)
- Anions recycled to lumen via Cl-/anion exchanger (also allows for Cl- uptake)
- Cl- crosses basolateral membrane via K+/Cl- cotransporter
- Cl- also leaves lumen by paracellular pathway: transepithelial membrane potential (lumen positive); additional Na+ reabsorption
Thin Descending portion of loop of Henle
HIGHLY permeable to WATER
allows extensive water reabsorption
Thick Ascending portion of loop of Henle
IMPERMEABLE to water but permeable to Na and Cl (allows salt reabsorption)
Thick Ascending Loop of Henle
Na/K+/Cl- transporter
- driven by Na gradient
- electroneutral
- inhibited by furosemide (loop direutic)
- K+ exits lumen, creating lkumen positive trans epithelial potential that drives paracellular uptake of cations
High ADH
distal and CD
high water permeability > extensive reabsorption of water > concentrate urine
Low ADH
distal and CD
low water permeability > extensive excretion of water > dilute urine
Early Part of Distal Tubule
- Impermeable to water
- Na+ and Cl- reabsorbed via Na+/Cl- cotransporter (inhibited by thiazide diuretics)
- Na+ crosses basolateral membrane via Na+/K+ ATPase
- Cl- crosses basolateral membrane via Cl- channels
Principal Cells
absorb Na+ via apical Na+ channels
Principal Cells of Late Distal Tubule and CD
- Na+ channels inhibited by amiloride diuretics
- Principal cells have K+ channels, allowing secretion into lumen
- Principal cells have ADH-sensitive water channels that help w/ reabsorption
Liddle’s Syndrome
mutation in Na+ channel > ↑ reabsorption > ↑ BP
Diabetes Insipidous
no ADH response
Intercalated cells of Late Distal Tubule and CD
- a-intercalated cells have apical proton pump (V-ATPase) that pumps H+ into the lumen
- a-intercalated cells also have basolateral HCO3-/Cl- exchanger
vacuolar H+ ATPase (V-ATPase)
Responsible for H+ secretion into a-intercalated cells in DT and CD
renal tubule acidosis
Responsible for H+ secretion into a-intercalated cells in DT and CD
Genetic defects in renal specific isoforms of certain subunits
Agents that Increase NaCl and/or Water Reabsorption by the Renal Tubule
LOOK AT CHART
antidiruretic hormone (ADH)
stimulated by: low BP/volume or increased plasma osmolarity
Site: DCT/CD
no effect on NaCl
increases water reabsorption
starling forces
Movement of water (and solutes) into blood is favored by Pi and (pi)c and opposed by Pc and (pi)I
increase GFR
increase filtration of blood = increase protein concentration in blood in peritubular capillaries= increased movement of water (and solutes) into blood and decreased backleak into tubular fluid
prevents large changes in Na excretion when GFR changes