156 - Kidney Function 4 Flashcards
Area of the kidney where paracellular pathway takes place at the greatest rate
Proximal tubule (tight junctions are leakiest here)
How are cations absorbed in the tubule?
Solvent drag (as water is absorbed, drags solutes with it). Transporters.
Solutes particularly absorbed by early proximal tubule
Bicarbonate, amino acids, glucose
Solute particularly absorbed by late proximal tubule
Chloride
Why is bicarbonate preferentially absorbed at the early proximal tubule?
Sodium-bicarbonate transport.
NHE (sodium hydrogen exchanger) very active.
Leads to formation of HCO3- (from acid-base pathway, splitting of CO2 to bicarbonate and H+) through carbonic anhydrase pathway.
Cl- is left behind in the lumen after Na+ is reabsorbed
What in the late proximal tubule leads to greater Na+ reabsorption?
Cl- absorption leads to a +3mV luminal charge, which pushes Na+ into the epithelium
Inefficiency in Na+ reabsorption in the proximal tubule
Na+ can leak back into the lumen through the paracellular pathway.
Voltage of the early proximal tubule lumen
Negative
Why is Cl- absorbed at a greater rate than Na+ in the late proximal tubule?
Na+ has been absorbed in the early tubule and Cl- has been left behind, leading to a greater Cl- gradient in the late tubule.
Effect of positive voltage in lumen of late proximal tubule
50% of Na+ reabsorption is paracellular, 50% is transcellular, because positive Na+ follows electric gradient (goes towards relatively negative epithelium).
How is Cl- reabsorbed in the late proximal tubule?
Cl-/base exchanger on apical membrane, Cl-/K+ cotransporter and Cl- channel on basal membrane.
Paracellular pathway.
Na+ in thin ascending limb
Na+ is reabsorbed via passive diffusion in response to concentration gradient.
Paracellular pathway.
Thick ascending limb reabsorption
Continues reabsorbing NaCl.
Reabsorbs 25% of filtered NaCl
Concentration of filtrate in the distal convoluted tubule
100mOsM
Part of nephron that all diuretics work on
Na+ transporter on apical membrane
Part of nephron that loop diuretics act on
Na/K/2Cl cotransporter (electrically neutral)
Part of nephron that Thiazides work on
NaCl cotransporter in distal tubule (electrically neutral)
Part of nephron that Amiloride works on
Epithelial sodium channel in the collecting duct
Why does the concentration of filtrate drop in the thick ascending limb?
Tight junctions are permeable to Na+, but not to water.
Na/H exchange is still occurring apically.
What helps balance charge of reabsorbed Na+ in the thick ascending limb?
K+ channel on apical membrane allows K+ to leak into lumen
Distal tubule ion exchange
Further NaCl transport (cotransporter).
Why does Frusemide need to be given with K+ supplements?
Inhibits Na/K/2Cl transporter in ascending limb of loop of Henle.
Not reabsorbing as much K+.
Na movement in distal tubule
Entirely transcellular
Cortical collecting tubule ion exchange
ENaC is only Na+ channel.
K+ channel lets K+ diffuse into the lumen.
What drives all Na+ (and therefore ion) diffusion?
Active 3Na+/2K+ pump on the basolateral surface
Endogenous organic acids
Want to retain these in the kidney.
Mono-carboxylates (organic acids) reabsorption
Apical membrane Na-dependent cotransporter.
Basolateral membrane H+-dependent cotransporter (MCP1)
Di- and tri-carboxylate (organic acids) reabsorption
Apical membrane: Na-dependent cotransporter NaDC1
Basolateral membrane: Organic Anion Exchanger eg ROAT1
How can xenobiotics be reabsorbed?
All use ROAT1 to enter late proximal tubule cells (secretion).
Cross apical membrane with another organic anion exchanger.
Countercurrent exchange system of the kidney
At any time, descending limb concentration is ~200mOsM higher than ascending limb. Equilibrates ECF with descending limb.
Descending limb is only ion-permeable, so loses ions into the ECF, which go into the vasa recta (which flow antiparallel to loop of Henle fluid).
This concentrates blood in vasa recta, which pull water out of descending limb when they run beside the descending limb.
What is absorbed in descending limb?
Only water
What is reabsorbed in the thick ascending limb?
Only ions
How is hypo-osmotic filtrate made in the ascending limb?
Wall is water-impermeable.
Active reabsorption of ions.
Concentration of urine in collecting duct
Duct travels through very hyperosmolar ECF of kidney.
Vasopressin increases water-permeability of wall.
Water is carried away by vasa recta capillaries.
Effect of absend vasopressin on collecting duct
Collecting duct is impermeable to water, urine remains dilute (100mOsM, same as in distal tubule)
Stimuli for vasopressin release
Osmolarity.
ECF volume is an even more powerful stimulus.
Effects of plasma angiotensin II 1 2 3 4 5 6 7
1) Arteriolar vasoconstriction
2) Increased cardiovascular response, from stimulation of cardiovascular control centre in the medulla oblongata
3) Preferential constriction of efferent arteriole
4) Increased proximal tubule Na+ reabsorption (stimulates NHe)
5) Acts on glomerular mesangial cells to regulate glomerular filtration.
6) Hypothalamus releases more vasopressin, increases thirst.
7) Adrenal cortex releases aldosterone, which increases Na+ reabsorption
