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‫﴿و ما أوتيتم من العلم إال قليال﴾‬
‫صدق هللا العظيم‬
‫االسراء اية ‪58‬‬
By
Dr. Abdel Aziz M. Hussein
Lecturer of Medical Physiology
10 %
65-70%
5%
15%
Less than 1 %
A) In proximal tubules:
• By osmosis 2ry to reabsorption of solutes.
• The osmolarity of paracellular spaces is ↑ed by:
1) 1ry active Na+ reabs. and accompanying Cl- and
HCO3-.
2) 2ry reabs. of substances as glucose & amino
acids
Lumen
Na , Cl,
HCO3
Glucose,
amino
acids
PTC
spaces
Na , Cl,
HCO3,
Glucose,
amino acids
PTC
Increased
osmolarity
Water
Water
Na , Cl,
HCO3,
Glucose,
amino acids
B) In Loop of Henle:
In DLH
• By osmosis 2ry to high osmolarity of medullary
interstitium
• DLH contain special water channel but are not
controlled by ADH as that of collecting ducts.
In ALH:
• Totally impermeable to water.
High
medullary
interstitial
osmolarity
Water
B) In Distal tubules and CDs:
1. Early distal tubules is hardly permeable to water
2. Late distal tubules and CDs are permeable to
water in the presence of ADH
• Reabsorb about 10 % of filtered load of water or 2/3
of the amount coming from ALH (2/3 of 15-17% of the
filtered load of water).
• So, medullary CD receives 5% of GFR all is
reabsorbed except 1% (0.5 -1 ml/min) which forms
the urine.
ADH
Water
Aldosterone
ADH
10 %
65-70%
4.1%
15%
0.9 %
1.1 ml/min or
1.5 L/day
10 %
65-70%
4.1%
15%
0.9 %
1.1 ml/min or
1.5 L/day
Obligatory
87.5 %
12.5 %
Low Or no ADH
16 ml/min or
27.5 L/day
Obligatory
99.8 %
0.2 %
High
ADH
0.25 ml/min or
400 mL/day
Water
Input
Water
Output
Thirst
Kidney
under ADH
↓ blood volume
(Hypovolaemia)
Angiotensin II
Thirst Center
Thirst
sensation
↑ plasma osmolarity
(Hypertonicity)
Increased water intake
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↑ plasma osmolarity
↓ blood volume
Stimuli for thirst:
1) Hyperosmolarity:
• ↑ Plasma Osmolarity by 2-3%  strong desire to drink.
2) Blood volume:
• ↓ Blood Volume by 10-15% → evokes thirst as that
induced by ↑ 2-3% in plasma osmolarity.
3) Angiotensin II by direct action on thirst center.
4) Dryness of the mouth
5) Water metering in the stomach that sense the need
for water.
↓ blood volume
(Hypovolaemia)
Posterior pituitary
ADH secretion
Angiotensin II
↑ plasma osmolarity
(Hypertonicity)
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↑ plasma osmolarity
↓ blood volume
↓ Urine volume
• The kidney can make diluted urine up to 25-50
mosmol/L or concentrated urine up to 1200-1400
mosmol/L.
• For making either diluted or concentrated urine, the
kidney must do an osmotic work which is exerted by
the loop of Henle (specifically by thick ALH).
• Fluid enters the loop of Henle is isotonic from PT and
leaves it hypotonic to DT.
• The excess solutes (NaCl and Urea) are entrapped
in the medulla making what is called the medullary
gradient.
• In overhydration i.e. presence of excess water in the
body, urine must be diluted (hypotonic urine), so, the
fluid delivered to connecting tubule and collecting duct
is excreted as such without water reabsorption (due to
decrease of ADH secretion).
• In dehydration, lack of water or excess solutes to
water, water must be absorbed in the connecting
tubules and CD and urine is concentrated, to
preserve water.
Requirement for the kidney to make diluted or
concentrated urine
• 1) Formation of medullary gradient.
• 2) Maintenance of this medullary gradient.
• 3) Role of ADH
Def.
• It is a gradual increase in medullary
osmolarity from 300 mosmol/L at the corticomedullary junction up to 1200-1400
mosmol/L at the tip of renal papillae
Causes of medullary gradient:
• 1) Counter-current multiplier system.
• 2) Urea recycling
Def.
• It is the system in which the inflow runs parallel, in close
proximity and in counter direction to the outflow.
Requirements:
i) Active transport of NaCl at thick ALH:
•
The active NaCl reabsorption is the key factor of development of medullary
gradient due to;
a) Makes horizontal gradient ( ) ALH and surrounding interstitium, at any level, by
about 200 mosmol/L→ help absorption of water from DLH.
b) As ALH is impermeable to water → delivery of diluted fluid to the DCT& CDs.
• In the presence of ADH, water is absorbed without urea in the CTs, CCD and
outer MCD  ↑ urea concentration in papillary CD  urea is reabsorbed into
medullary interstitium  ↑ its osmolarity (shift of horizontal to vertical gradient).
c) The high inner medullary osmolarity induced by urea, causes water reabsorption
from DLH.
• This makes concentrated fluid at the bend of loop of Henle  helps passive
diffusion of NaCl from thin ALH to the medullary interstitium, further increasing its
osmolarity.
• So, the horizontal gradient is shifted indirectly into a vertical one i.e. from
cortico-medullary junctions to the tip of medulla.
Requirements:
ii) Different water & solute permeability of loop of Henle:
• DLH permeable only to H2O  H2O reabsorption by
surrounding hyperosmolarity of medullary interstitium 
gradual ↑ in the osmolarity of the fluid flowing in DLH.
• Thin ALH permeable only to solutes→ NaCl- reabsorption
passively into medullary interstitium (NaCl concentration at
the bend & thin ALH is 1120 mosmol/L while NaCl outside is
600 mosmol/L).
iii) Counter-current flow in the loop of Henle:
• This shift the horizontal gradient into vertical one.
Requirements:
iv) Role of distal tubule and CCD
• About 2/3 of water delivered to connecting tubules and CCD
is reabsorbed (about 10 ml from 15 ml).
• This makes hypotonic fluid from loop of Henle isotonic in
the cortex.
• So, little fluid is delivered to medulla  increasing urea
concentration  diffusion of urea to medullary interstitium 
increasing medullary osmolarity.
• Accordingly, medullary washout will occur if excess fluid is
delivered to it due to absence of water reabsorption in
connecting tubule and CCD as in absence of ADH.
10 ml of water
15 ml of water
5 ml of Water
Requirements:
v) Osmotic equilibrating device of medullary CD:
• To help reabsorption of urea & solutes from
collecting duct to medullary interstitium, so
increasing deep medullary osmolarity.
•
•
•
•
•
•
•
1) Magnitude of the single effect:
2) Flow rate in the loop of Henle:
3) The length of loop of Henle:
4) The percentage number of long loop of Henle:
5) Presence or absence of ADH.
6) Rate of medullary blood flow in the vasa recta:
7) Amount of urea available:
• Why the cells of the medullary structures don’t
shrink by the surrounding high osmolarity?
• The shrinkage is avoided by intracellular formation
of organic solutes that increase intracellular
osmolarity as inositol, betaine and glucerophosphoryl choline.
Factors affecting Urea Clearance (Excretion):
1. Filtered load of urea (Purea X GFR)
2. Plasma concentration (Purea) 2) GFR
• The more the filtered load, the more the urea excretion
3) Tubular flow rate (TFR):
• Urea excretion is flow-dependent, and so it is increased
in diuresis. The more urine flow rate or more tubular flow
rate, the less urea reabsorption and the more urea
excreted.
• Normally, clearance ratio for urea is about 1/2 i.e. half the
clearance of inulin.
1) In proximal tubule:
• Passive reabsorption according to reabsorption of water.
• At the end of PCT, its concentration is 6 mmol/L (as the
plasma).
• At the end of pars recta (segment 3), its concentration is 20
mmol/L due to reabsorption of water without urea.
2) In loop of Henle
• In DLH water is reabsorbed without urea & some urea diffuses
from interstitium while in thin ALH, there is passive secretion of
urea from interstitium to tubular lumen.
• In thick ALH: it is impermeable to urea.
– At the bend of short-looped nephrons, urea concentration
inside the loop is 40 mmol/L.
– At the bend of long-looped nephrons, its concentration is 80
8
20
40
80
• It is the cycling of urea between the inner medullary
CD "PCD"  inner medullary interstitium  DLH and
thin ALH  thick ALH  DCT  connecting tubules
 CCD  MCD  PCD  interstitium again and so
on.
1. Entrapping of urea in the interstitium of inner medulla.
2. Augmentation of its concentration in the inner medulla.
Both 1 and 2 increase the medullary gradient.
N.B. less blood flow to medulla help medullary building up, while
high blood flow to medulla leads to medullary washout of
solutes.
• Vasa recta (VR) is characterized by:
1. Counter-current exchanger system.
2. Capillary wall is permeable to solutes & water. So,
solutes enter DVR and water leaves it while in AVR,
solutes leave and water enters it.
3. Long capillaries High viscosity of the blood
4. High viscosity of blood
• This causes sluggish blood flow in vasa recta
1. Steady state: VR reabsorb equal amount of water
and solutes so, neither medullary washout nor
building up of high gradient are required as in
euvolumic state.
2. The VR reabsorb more water than solutes during
building up of medullary gradient or when high
medullary gradient is required as in dehydration
and decrease of ECF volume.
3. VR reabsorb more solutes than water , when high
medullary gradient is not so important as in
overhydration and increase in ECF volume
(washout of medullary gradient is required).
THANKS