Segments of the Nephron Flashcards
Renal corpuscle
Contains glomerulus and Bowman’s capsule
Rapid ultrafiltration from blood capillary of glomerulus into Bowman’s space (or, urinary space). Pretty much everything but proteins (albumin) and RBCs gets through.
Urinary pole leads to PCT, vascular pole has afferent/efferent arterioles
Proximal convoluted tubule
Reabsorbs 65-70% of filtrate
Isosmotic reabsorption (water and solute absorbed has same osmolality as filtrate)
Glucose, AAs, some organic acids 100% absorbed
Other organic acids/bases 100% secreted
Urea 50% reabsorbed passively
Early PCT reabsorbs NaHCO3 and late PCT reabsorbs NaCl
NH4+ secreted here, that eventually helps excrete H+ if you get acidosis
Has glomerulotubular balance (if GFR increases reabsorption increases)
Thin descending limb of loop of Henle
Passively permeable to water and small solutes (NaCl, urea)
Water moves out and solutes move in and tubular fluid becomes more concentrated (hyperosmotic) as it flows down
Thin, flat epithelia and no mitochondria
Contributes to countercurrent multiplier
Thin ascending limb of loop of Henle
Not permeable to water, but is passively permeable to NaCl
Solute moves out (without water) so tubular fluid becomes less concentrated (hyposmotic) as it flows up
Thin, flat epithelia and no mitochondria
Contributes to countercurrent multiplier
Thick ascending limb of loop of Henle
Reabsorbs 25% of filtered solute but impermeable to water
Highest Na/K ATPase activity in the kidney (basolateral membrane)
Is load dependent (the more Na+ delivered, the more it will reabsorb)
Dilutes urine
Contains macula densa cells
Sets up countercurrent mutiplier
Has glomerulotubular balance
Juxtaglomerular apparatus (JGA)
Macula densa in the thick ascending limb of loop of Henle touch the glomerulus and the juxtaglomerular cells of the afferent arteriole
When renal arterial pressure, Na+ delivery to distal tubule decrease (or when sympathetic tone increases), macula densa cells sense Na+ decrease and tell JG cells to secrete renin, which activates RAAS system to increase water reabsorption, increase BP, increase GFR, etc
Distal convoluted tubule
Reabsorbs 5% of filtered solute but not much water
Dilutes urine further
Similar to thick ascending limb of loop of Henle, but different transport mechanisms
Hormonal regulation of Ca2+ reabsoprtion
Has GT balance
Collecting tubule
Principal cells: most common type (65%); regulate K+, Na+, H2O; acted on by aldosterone and ADH; dilute/concentrate the urine
Type I (alpha) intercalated cells: secrete H+ and reabsorb K+
Establishes steep gradient, but have limited capacity (quality control at the end of long assembly line)
Early proximal convoluted tubule reabsorption of Na+
Apical membrane:
1) Na+ channels
2) Na+ cotransporters w/glucose, AAs, phosphate
3) Na/H antiport (MOST IMPORTANT)
Basolateral membrane: Na/K ATPase pumps Na+ into plasma against gradient
Lumen is -4mV because of Na+ reabsorption
Remember, HCO3- reabsorbed with Na+ (electroneutrality!) from CO2 inside the cell
Late proximal convoluted tubule reabsorption of Na+
1/3 of Na+ and water have already been reabsorbed but [Na+] still the same!
Not much glucose, AAs, etc left for cotransport with Na+
BUT, Cl- concentration in lumen is increased 20% compared to plasma concentration so there is steep electrochemical gradient for its passive reabsorption. Lumen at +4mV because of Cl- moving into cell in early PCT, but CHEMICAL gradient forces Cl- into cell anyway, and Cl- brings Na+ with it (electroneutrality):
1) NaCl through leaky-ish tight junctions (30% of reabsorption in PCT)
2) Cl/Formate exchange with Na/H and HF leaving cell as H+ and F- drives this
Early proximal convoluted tubule reabsorption of Cl-
Cl- not preferentially absorbed in PCT (HCO3- is), but goes through VERY leaky tight junctions because lumen is -4mV compared to cell
Water reabsorption in PCT
Standing gradient hypothesis (Jared Diamond) across lateral membranes (between cells–so much more SA than other membranes) that has isosmotic in it. Closed at lumen end but open at basolateral end, and most Na/K ATPase at basolateral end so water diffuses there! (Costanzo says it is high oncotic pressure of peritubular capillary that draws fluid in from lateral space)
With aquaporins in lateral membranes
Also water is passively reabsorbed (water follows salt) in luminal membrane and basolateral membrane
Urea reabsorption in PCT
As solute and water are reabsorbed in the PCT, a concentration gradient for urea to move into the plasma arises (more urea in PCT than in capillaries)
50% of urea diffuses down its gradient and is reabsorbed using channels, but not that permeable so only 50%.
Note: urea not reabsorbed here does not get reabsorbed again until collecting duct
Note: urea transport proteins in collecting duct inculde ADH-activated urea channels
Glomerulotubular balance
Increased GFR causes proportionate increase of reabsorption (percent of filtrate reabsorbed is constant, so if more filtrate, more reabsorbed)
How: more fluid filtered out of glomerular capillaries, leaving higher leftover protein concentration and oncotic pressure of blood that ends up in peritubular capillaries, and that causes higher reabsorption (Increase GFR –> increase filtration fraction –> increase oncotic pressure in peritubular capillaries –> increase reabsorption)
Dependent on glucose, AA, HCO3 for increased cotransport of Na+
Prevents increased GFR from overwhelming downstream transport capacity
PCT has GT balance (it’s so awesome for being able to do this!)
How is GT balance in the PCT affected by volume state?
Hypervolemia: increased ECF volume –> increased extracellular water dilutes plasma proteins –> decreased oncotic pressure in capillaries but increased hydrostatic pressure –> increased hydrostatic pressure of interstitial fluid around PCT –> increased leakiness of tight junctions –> Na+ goes back into lumen through tight junctions and brings water with it –> decreased reabsorption of Na+ and water –> more Na+ and water excreted, and get rid of volume!
How else does volume modulate GT balance in the PCT?
1) Angiotensin II (from RAAS responding to low volume state) stimulates Na/H antiport to increase Na+ reabsorption with HCO3- (can cause contraction alkalosis!)
2) Direct alpha1 adrenergic innervation of PCT stimulates Na/H antiport and Na/K ATPase to increase Na+ reabsorption
How does the amount of filtrate reabsorbed in the PCT remain constant?
1) Autoregulation of GFR
2) Tubuloglomerular feedback in every individual nephron
3) Glomerulotubular balance when GFR does vary
“Diluting segment”
Thick ascending limb of loop of Henle + Early distal convoluted tubule
Impermeable to water, but reabsorbs 30% of salt
Luminal fluid always hypoosmotic/dilute (100 mOsml)
Tight tight junctions allow significant electrochemical gradient before transport is stopped by ionic backfluxes
How is Na+ reabsorbed in the thick ascending limb of loop of Henle?
Na/2Cl/K pumps ions in, and K+ pumped back out so generates luminal membrane potential of +20mV compared to cell
Na/K ATPase brings Na+ into plasma
Note: ADH stimulates Na/2Cl/K pumps
How do Mg2+ and Ca2+ get reabsorbed in the thick ascening limb of loop of Henle?
Luminal membrane potential of +20mV drives Mg2+, Ca2+ (and Na+) into tight junctions to be reabsorbed
Note: Na/2Cl/K pump leads to net +20mV charge because 2Cl- and 1Na+ INTO cell
Which diuretics work on thick ascending limb of loop of Henle, and how do they work?
Loop diuretics (furosemide and bumetanide): bind Cl- site on Na/2Cl/K transporter
Causes loss of Mg2+ and Ca2+ because electrical gradient is abolished so they can’t be passively reabsorbed anymore
Cause secretion of K+ (hypokalemia) because more Na+ delivered to principal cells of collecting tubule and they reabsorb a lot of Na+, which secretes lots of K+
Get rid of the countercurrent multiplier
What is the mechanism of GT balance in the thick ascending limb of loop of Henle?
Cl- is rate limiting for the Na/2Cl/K pump, but when amount of fluid in segment is increased and thus Cl- is increased, the pump works faster to reabsorb more
How is salt reabsorbed in the distal convouted tubule (DCT)?
Na/Cl cotransporter driven by Na+ gradient, then Na/K ATPase
Tight junctions are actually tight so so paracellular (lateral) ion reabsorption
No electrochemical gradient
Which diuretics work on DCT and how?
Thiazide diuretics: block NaCl transporter by binding Cl- site –> lose salt –> decrease plasma osmolality –> decrease ADH secretion to get rid of more water
You’ll reabsorb more Ca2+ as a result, because decreased Na+ on the inside of cell makes Ca2+/3Na+ antiporter want to bring Na+ into the cell
How is Ca2+ reabsorbed in the DCT?
Hormonally regulated Ca2+ reabsorption
Ca2+enters by vitamin D induced Ca2+ binding protein –> pumped uphill across basolateral membrane by Ca2+/3Na+ antiporter
Parathyroid hormone regulates additional mechanisms to reabsorb Ca2+ here
What are the differences between GT balance in the PCT and in the diluting segment?
No water reabsorption to follow in the diluting segment!
In both cases obviously more flow means more salt reabsorption, but because water doesn’t follow in diluting segment, get diluted tubular fluid
How do principal cells of the collecting tubule reabsorb Na+?
-50mV gradient of lumen to cell
Aldosterone diffuses into nucleus to enhance tx and synthesis of luminal Na+ channels and basolateral Na/K ATPase to help Na+ be reabsorbed (takes about 1 hour)
Only modulates reabsorption of last 1-2% of Na+, but this is still very important
How is K+ secreted from principal cells in the collecting tubule?
Reabsorbing Na+ on basolateral side brings in K+ from Na/K antiporter –> K+ secreted into lumen through channels
Aldosterone causes this because aldosterone increases reabsorption of Na+
Even though the collecting tubule has tight tight junctions, do any ions get through?
Yes, Cl- still gets through and is reabsorbed
How does the collecting tubule reabsorb water in the principal cells?
ADH released by posterior pituitary binds V2 receptors on basolateral membrane (ADH circulating in blood) –> cAMP/PKA pathway –> preformed aquaporins (AQP2) in vesicles inserted into luminal membrane –> water reabsorbed
ADH acts within a few minutes to increase water reabsorption
Which diuretics work on the principal cells of the collecting tubule?
K+ sparing diuretics:
Amiloride: block Na+ amiloride-sensitive channels so Na+ can’t be reabsorbed
Spironolactone: inhibits aldosterone (so no Na+ channels made/inserted so Na+ not reabsorbed)
How do the alpha-intercalated cells of the collecting tubule regulate K+, H+, and HCO3-?
Reabsorb K+ and secrete H+ with K/H ATPase
Also secrete H+ with H+ ATPase
HCO3- reabsorbed with HCO3-/Cl- antiporter
Note: cannot transport Na+ or water
What do the beta-intercalated cells of the collecting tubule do?
Same as alpha-intercalated but with NO K/H pump BASOLATERAL H+ pump, so you get H+ in and HCO3- out
Used if you have alkalosis and need to retain H+
