Reabsorption and the Nephron 316 and 318

1
Reabsorption and the Nephron 3/16 and 3/18

• How does solvent drag pull water out of the
  filtrate through transcellular and paracellular
  routes?
• How does solvent drag explain the diuresis
  associated with diabetes?
• What is the function of the Loop of Henle?
• How does the Loop function as a Counter Current
  Multiplier?
• What is the function of the Distal Convoluted
  Tubule?
• What is the function of the Collecting Duct?
• How does the collecting duct help control the pH
  of your blood with our beloved enzyme carbonic
  anhydrase?
• Why is it impossible to modify urine quality
  after it leaves the collecting duct?
• What happens when glucose remains in the urine?

2
Polar Molecules, such as glucose or sodium, carry
spheres of hydration with them when they are
reabsorbed into the blood or are NOT reabsorbed
and remain in the urine causing diuresis.
3
The Proximal Convoluted Tubule (PCT) is the ONLY
place in the nephron that can reabsorb glucose
from the filtrate. Why might the urine taste
sweet if your diabetes mellitus is
uncontrolled? Why might DM cause diuresis (large
amounts of urine)?

• Na and Glucose are co-transported by enzymes
  have a transport maximum-
• Only so many glucose molecules can be removed
  from the filtrate/minute (Tmax).
• Glucose freely filtered from the blood-
• Only PCT can reabsorb glucose-
• Glucose has a sphere of hydration-
• IF the Tmax passed glucose stays in urine
  forever-
• Each glucose that stays in urine carries water
  with it!
• Oligouria?Dehydration?Why are you so thirsty?
• What will posterior Pituitary try to do with ADH?
  
• What will adrenal cortex try to do with
  aldosterone?
• Diabetes mellitus-VS.-Diabetes insipidus-

4
Concentration gradients and semipermeable
membranes If there is more of a polar molecule
on one side of a membrane than the on other,
several things could occur.

• The polar molecule (solute) could pass through
  until both sides have equal solute
  concentrations.
• If polar molecules pass through, they may carry
  water hydrogen bonded to them
• If polar molecules pass through, they may attract
  water when they get to the other side.
• If the pores of the membrane are too small and do
  not allow the solute to pass, they MAY allow the
  solute to diffuse via transcellular or
  paracellular pathways.

5
LOOP OF HENLE IS AN AMAZING COUNTER CURRENT
MULTIPLIER FOR SALTS AND UREA. (180 L ?about
35L)(Extra credit figure it out in class? you
get a Nobel Prize and a A for AP212 ?)

• Loop reabsorbs 15-20 of water fine tuning of
  water reabsorption only occurs if salts pumped
  out of ascending loop!
• Ascending Loop (THICK) water impermeable. Na/K
  ATPase moves intracellular Na into interstitium,
  so Na is pulled into cell from filtrate along
  with K and 2 Cl- ions by a NaK-2Cl- pump.
• Descending Loop (THIN) Very permeable to water
  and salts
• Idea 1 Salts are pumped into the interstitium
  from the thick Ascending Loop that drag H2O out
  of permeable thin Descending Loop
• Idea 2 Reabsorbed water passes into the
  capillaries of the vasa recta out before water
  can diffuse back into the filtrate (whisk away).
• Idea 3 Concentration gradient along Loop
  established by a Counter Current Mechanism along
  length of Loop.
• Idea 4 Cortical vs. Medullary Loops degree of
  water reabsorption dependent on length of Loop.
• Volume of filtrate is further decreased UREA ALSO
  appears to be critical for dragging water away
  from the filtrate! Concentration gradients
  established here help reabsorb water from
  collecting duct!

6
The Loop of Henle only works if the thick
ascending side is pumping NaCl and KCl (very
polar) out of the filtrate into the interstitium.
This drags water out of the descending side
(water attempts to dilute the salts)! Water is
dragged into the protein-rich plasma vasa recta
(protein acts like sponge) and the reabsorbed
water is whisked away.
7
The longer the Loop of Henle, the greater the
osmotic gradient and the greater amount of water
you can remove from the descending loop AND
collecting duct! Note that urea is being pumped
out and recirculated in the Loop, urea helps draw
extra water out of the collecting duct if the CD
is H2O permeable and if the interstitium is
hyperosmotic (salty).
8
Counter Current Multipliers Why do short
cortical loops produce dilute urine? Why are
long medullary loops best at producing
concentrated urine? Remember that the gradient
established by the ascending loop can also pull
water from the lumen of the collecting duct.

• Short Loop

• Long Loop

9
Why is reabsorbed fluid whisked away from the
tissues around the nephron or collecting duct?

• Hydrostatic pressure in capillary 15 mmHg out
  of capillary
• Remember the blood entering this capillary was
  filtered in the glomerulus!
• Hydrostatic pressure in FILTRATE -5 mmHg out of
  capillary
• Remember pressure gradient is required to drive
  filtrate towards the bladder!
• Osmotic pressure in plasma -28 mmHg into
  capillary
• Remember the number of proteins in this blood
  has not changed!
• Osmotic pressure in filtrate 0 mmHg essentially
  zero!
• Hopefully NO protein was filtered!
• Net Filtration Pressure
• (15 out)(-5 in) (-28 in) (0) 15 -33
  -18 mmHg INTO capillary!
• Therefore fluid in the interstitium wants to
  enter the blood in the capillary!
• Remember! The nephron or collecting duct must be
  made permeable to water for this to occur!

10
DISTAL CONVOLUTED TUBULE CAN REABSORB ABOUT 10
OF THE FILTRATE AND ACTIVITY IS HORMONE DEPENDENT.

• When the filtrate enters the DCT it is not too
  different from the plasma in terms of osmolarity!
  
• Aldosterone acts on the DCT (and collecting duct)
  and activates the Na/K-ATPase and causes active
  reabsorption of Na out of the filtrate
• Na/K-ATPase trades 3Na from filtrate for 2
  K, this conserves Na in the body at the cost
  of K!
• Because sodium has a LARGE sphere of hydration
  and because potassium has a SMALL sphere of
  hydration, water is conserved if sodium is
  conserved (reabsorbed). V.I.P.!
• If sodium is not removed from the filtrate in the
  DCT, then less water is removed from DCT.
• Aldosterone Absence ?body loss of Na, ?urine
  Na, ?urine volume.
• DCT is also important for calcium reabsorption, a
  hormonal effect related to increased plasma
  parathyroid hormone and calcitriol.
• Finer tuning of H balance in body also begins
  here.

11
COLLECTING DUCTS PROVIDE THE LAST PLACE FOR THE
FINE TUNING URINE VOLUME, pH, AND SALT BALANCE.

• URINE CONTENT IS FINE TUNED BY TWO C.D. CELL
  TYPES.
• Principle Cells reabsorb Na and secrete K into
  urine (Na/K-ATPase) 3Nafrom cell move into
  interstitium and 2K from interstitium move into
  cell SO. Na passively diffuses into cell from
  lumen in exchange for K
• Water follows sodium and is thus conserved at
  the cost of potassium loss
• Intercalated Cells several options to prevent
  acidosis in blood!
• Direct Proton Secretion H-ATPase direct
  pumping into lumen causing the blood pH to become
  less acidic, urine becomes more acidic.
• Proton Trading (Indirect H removal) Na or K
  in lumen exchanged for H in cell, as a result
  blood has fewer H and urine becomes acidic
  (Aldosterone Dependent).
• Anytime H appears in the urine, the urine
  volume may increase (potential for dehydration).

12
The Importance of Aquaporin

• The Importance of ADH (Vaspresssin) from the
  posterior pituitary.
• Hormone ADH moves Aquaporin to plasma membrane.
• ADH causes the collecting duct to be permeable to
  water!

13
Golden Rule If you want to lose something,
filter it then dont reabsorb it, just remove
water and concentrate the leftovers. You can
filter or secrete protons into filtrate to
remove them!A similar processes occur in the PCT
and collecting duct
Intercalated Cells of CD
Acetazolamide (Diamox) is a drug that is filtered
and blocks carbonic anhydrase, what will happened
to urine/blood pH?
14
THE DISTAL CONVOLUTED TUBULE AND COLLECTING DUCTS
HAVE THREE DIFFERENT WAYS TO FINE TUNE OR
BUFFER CHANGES IN BLOOD pH (prevent acidosis of
blood).

• 1) Secondary Active exchange in the PCT
• Interstitial Cl- exchanged for intracellular
  HCO3-
• Keep the base, lose the acid
• 2) Aldosterone can move a H/Na-exchanger to the
  plasma membrane of collecting duct cells
• -Dump H/Save Na
• 3) Na/K-independent H-ATPase in Collecting Duct
• Directly pump protons into lumen
• Chloride ions chase after H in the filtrate for
  electrical neutrality. H-ATPase pumps up to a
  X1,000 gradient
• Urine pH limit is a pH of about 4.5 (about like
  vinegar).
• This is the absolute limit of our pH
  compensation.
• If you cant compensate for changes in blood pH
  after all these
• H secretion mechanisms are at maximal activity?
  Hello Comma!

15
Collecting Duct is the last chance to fine-tune
the quality of the urine.

• Once urine leaves CD where does it go?
• Urine enters the minor calyx?major
  calyx?ureter?bladder
• Urine exits body when smooth muscle of bladder
  contracts and urine is forced out the urethra.
• Once urine leaves CD its qualities cannot be
  altered!
• There are no pumps of pathways to alter the
  quality of the urine after it leaves the
  collecting duct!

16
WHY WAS THE TASTE OF SUGAR IN THE URINE ONE OF
THE FIRST BIOCHEMICAL TESTS FOR DIABETES
DIAGNOSIS?

• Enzymes have a transport maximum-
• Glucose freely filtered from the blood-
• Only PCT can reabsorb glucose-
• Glucose has a sphere of hydration-
• Tmax passed glucose stays in urine-
• Polyuria (large urine volume) gtgt Dehydration
  gtgtgtgtgt
• Diabetes Mellitus (sweet taste)- Insulin Problem
• VS.
• Diabetes Insipidus (no sweet taste)- ADH Problem
• Why can a large urine volume rapidly become FATAL?