DR. AMIR BAHADUR
Re-absorption and Secretion by
Nephron
Important to remember
Different types of cells and different
structures at different parts of
nephron causes different changes to
the filtrate
Difference of osmolality in various
parts of nephron causes changes to
filtrate
Different hormones/chemicals exert
their actions
Few basic facts
120mL/min-----GFR
1mL/ min--------Urine formed
119mL/min------Re-absorbed
172L/day---- filtered
1.5L/day------urine formed
Approx 170L---- re-absorbed
PCT--- series of events
On baso-lateral membrane are 3Na/
2K ATPase. 3 Na out to interstitium,
2K inside to PCT cell
K- leaky channels---- K outside to
insterstitium
Above two events, set the start by
Negative electro-chemical state inside
the PCT cell
Sodium in PCT
Concentration gradient for sodium
Electric gradient for sodium
Sodium transporters (co-transporters)
Facilitated transport
Other arm of co-transporter can attach
glucose, chloride or amino acid.
Sodium is transported from lumen to PCT
cells via facilitated diffusion
65% sodium is re-absorbed in PCT
Glucose & Amino Acids in PCT
Co-transporters in the luminal brush border
with one arm for sodium and other for
glucose and amino acid.
Glucose and amino acids are transported via
secondary active transport from lumen to the
PCT cells.
100% of glucose and amino acids are re-
absorbed in PCT.
Chloride in PCT
Chloride is re-absorbed by same way as
glucose and amino acids.
Only difference is that preference is given to
glucose and amino acid and later chlorine is
take up.
Chloride re-absorption from lumen to PCT is
secondary active transport.
65% of chloride is re-absorbed in PCT
Bicarbonate
Not really re-absorbed
Rather replaced
hydrogen ions are transported from inside of
PCT to lumen of PCT via Na/H counter-transport
H combines with HCO3 in lumen to form
carbonic acid which dis-associates to CO2 and
H2O.
CO2 diffuse into PCT and combines with H2O to
form H and HCO3 ions.
HCO3 are transported to interstitium.
Water
Trans-cellular by the solutes
Para-cellular through tight junctions
Also solutes go along with water through
tight junctions
65% water is re-absorbed in PCT
Plasma proteins
Usually no plasma proteins are
filtered.
If filtered, PCT brush border has
affinity to get them attached
PINO-CYTOSIS and re-absorbed to
PCT cell
Secretion in to PCT lumen
Oxalates
Urates
Bile salts
Catecholamines
Toxins
Drugs
Secreted through special channels in the baso-
lateral surface. Transported across
concentration gradient from capp to
interstitium to PCT cell to Lumen.
Bit more in PCT
Minimal urea re-absorption across
concentration gradient.
PTH---- phosphate trashing hormone---
inhibits phosphate re-absorption.
Angiotensin II acts on PCT and increases
sodium re-absorption.
PCT cells also activates 25-hydroxy
cholecalciferol to 1,25 di-hydroxy
cholecalciferol
Leaving PCT
Same proportion of solutes and water are re-
absorbed in PCT hence; the osmolality of
filtrate entering and leaving PCT is SAME.
Though osmolality of the filtrate remains the
same, quantity of water and solutes
decreases.
Descending Loop of Henle
Cells are freely permeable to water
Cells are minimally active metabolically
No brush border and not much of ATPases
Descending limb is freely permeable to water
and interstitium is hyper-osmolar so water
re-absorbed.
20% of water here.
Descending Loop of Henle
Water going out, solutes retained and further
solutes coming in---- all across conentration
gradient.
Filtrate is concentrated so much that filtrate
osmolality equals that of interstitium.
Ascending Loop of Henle
Ascending Loop of Henle is totally
impermeable to water up to half of distal
convoluted tubule.
Hyper-osmotic filtrate reach thick part of
ascending Loop of Henle
Thick part of ALOH
On the baso-lateral membrane of this part,
3Na/2K ATPases and they create negative
gradient inside the cell.
The luminal membrane has Na-K-2Cl co-
transporter which pumps 1 sodium, 1
pottasium and 2 chlorides in to the cells from
lumen.
This sodium is pumped out in to the
interstitium by the ATPases.
Chloride moves to interstitium via chloride
channels.
Thick part of ALOH
K is getting in to the cell via Na/K ATPases
and also by Na-K-2Cl co-transport.
Cell is TOO RICH in potassium.
Potassium leaks to lumen via leaky channels
and make the lumen electro-positive.
This electro-positivity of lumen created by
potassium excess repels the calcium and
magnesium ions of the filtrate.
This repulsive force cause re-absorption of
Ca and Mg through tight junctions.
Thick part of ALOH
Processes of re-absorbing solutes with out
water causes…….
a)Increase of osmolality in interstitium
b)Decrease of osmolality in the tubules.
So this part is also called DILUTING SEGMENT
Thick part of ALOH
25% sodium is re-absorbed
25% chloride is re-absorbed
How much water?
Loop diuretics
Frusemide
Blocks Na-K-2Cl co-transport.
More sodium going next part
More Ca and Mg going next part
Less K going next part
Early Distal Convoluted Tubules
First half of EDCT have same roles as that of
ALOH
Diluting segment
At start of EDCT is present-------?
Mechanism of solutes re-absorption is bit
different.
EDCT
3Na/2K ATPases at baso-lateral membrane
Na/Cl co-transport channels at luminal
membrane instead of Na-K-2Cl co-
transporters
EDCT cell is negative inside, Na poor cell
5% Na is re-absorbed in DCT
Thiazide diuretic
Thiazide diuretics can block this Na/Cl co-
transporter and causes diuresis
Weak diuretic
Calcium conserving diuretic
EDCT---- calcium re-absorption
Para-thyroid hormonal acts on EDCT for re-
absorption of calcium.
PTH increases the activity of calcium pump
and Ca/Na exchanger at baso-lateral
membrane and make cell calcium poor
hence; increase calcium re-absorption via
calcium channels.
Late DCT & Cortical Collecting tubules
Discussed together due to same properties
Principal cells and inter-calated cells
Inter-calated Cells
Inter-calated cells are special cells meant for
hydrogen secretion.
H ions are produced in the inter-calated cells
by decomposition of carbonic acid and H ion
is transported to lumen by H-ATPases on
luminal membrane.
HCO3 produced is supplied to circulation
hence; called bicarbonate factory
Principal Cells
Baso-lateral membrane has 3Na/2K ATPases,
making cells Na poor.
Luminal membrane has Na and K channels.
Na moves to the principal cells across
electrical gradient.
Potassium moves out from cell to lumen
through K channels across electrical
gradient.
Principal Cells
Aldosterone acts on principal cells
Increases the ATPases activity on baso-lateral
membrane, making cells more poor in Na
and more rich in K
Also K channels are increased on luminal
membrane
Na channels are also increased and Na re-
absorption is increased.
Increased Na re-absorption, drag extra water
as well.
K- sparing Diuretics
Spironolactone
Blocks the action of aldosterone
Less K is secreted to the lumen.
Amiloride/ triamterine
Block Na channels
Less K is secreted to the lumen
Principal Cells
Anti-diuretic Hormone (ADH)
In absence of ADH, no water pores on
luminal membrane, water not absorbed.
In presence of ADH, water pores on luminal
side apparent and water re-absorption
increases.
Medullary Collecting Tubles
Some of the cells act as principal cells and
some act as inter-calated cells.
Final tunning of urine osmolality.
Special receptors for urea.
Urea is transported to inerstitium via
concentration gradient which is taken in to
the loop of Henle again and put in to the cycle
again.