Lecture – 7
Dr. Zahoor
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 Kidney
can excrete dilute or concentrated
urine depending on body state of hydration
 Body fluids are isotonic having osmolarity of
300 milliosmoles/liter (mOsm/l)
 Depending on body state of hydration kidney
can excrete urine having osmolarity from 100
– 1200 mOsm ( Normal urine Osmolarity is
about 500 – 600 mOsm )
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 Concentration
of urine is the function of
juxta -medullary nephron, which has long
loop of Henle which goes down deep in the
medulla
 Also, the vasarecta (capillaries) of juxta
medullary nephron follow the same deep
loop of Henle
 Flow in the both long LH and vasarecta is
considered counter current because flow in
two limbs of the loop move in the opposite
direction
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Juxta
medullary
and cortical
nephron
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Concentration of urine is due to
1. Juxta medullary nephron – long loop of Henle
establish (create) the vertical osmotic gradient
2. Vasarecta help to maintain (preserve) this
osmotic gradient
3. Collecting duct of all nephrons use the gradient
along with hormone vasopressin (ADH) to
produce urine of varying concentration
4. Urea also help in urine concentration
mechanism


This entire functional organization is known as
medullary counter current system
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 We
will discuss in detail each point
1- Medullary vertical osmotic gradient created by loop of Henle is called Counter
current multiplier
- Long loop of Henle in juxta medullary
nephron establishes the vertical osmotic
gradient. How?
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 As
filtrate is formed, it is isotonic in the PCT,
water is reabsorbed in PCT, secondary to Na+
active reabsorption
 When isotonic fluid enters the loop of Henle
changes occur in the descending and
ascending limbs of long henles loop
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 Descending
limb of long LH is highly
permeable to water due to AQP – 1 water
channel which are always open
 Descending limb is not permeable to Na+,
therefore, Na+ remains in the descending
limb of LH and its concentration (osmolarity)
increases
 Maximum osmolarity is at the tip of LH which
is 1200 mOsm/l
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 Ascending
limb of LH actively transports NaCl
out of tubular lumen into interstial fluid
 Ascending limb is impermeable to H2O
 As NaCl leaves and H2O remains, osmolarity
decreases in the ascending limb of loop of
Henle
 Fluid entering the DCT has low osmolarity of
100 mOsm/l
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Osmolarity
of fluid in
different
segments
of tubule
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IMPORTANT
 As Na+ is actively transported out of
ascending limb of LH, concentration
increases in the interstitial fluid surrounding
the loop of Henle
 This increased concentration in the
interstitial fluid achieved by loop of Henle
is known as Counter Current Multiplication
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12

A large, vertical osmotic
gradient is established in the
interstitial fluid of the medulla
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 What
is the benefit of fluid getting
concentrated in the descending limb of LH
and again diluted in the ascending limb of
LH?
Benefits are
- It establishes a vertical osmotic gradient in
the medullary interstial fluid
- This gradient is used by collecting ducts to
concentrate the tubular fluid (urine)
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 As
fluid is hypotonic as it enters CT, the
kidney can excrete dilute urine or it can be
concentrated in the CT. How ?
- ADH controls water reabsorption in DCT and
CT. About 20% of H2O enters DCT and CT, and
it is under control of ADH
NOTE - We know that in PCT 65% of water is
reabsorbed and in LH 15% of water is
reabsorbed
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 As
fluid enters the CT, it is hypotonic.
 For water reabsorption to occur in CT, Two
criteria must be met:
1. Osmotic Gradient across the CT – it is
there as interstial fluid is concentrated by
LH- counter current multiplication
2. Collecting tubule must be permeable to
water, it is there due to presence of ADH
(normally DCT and CT are impermeable to
H2O)
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 How
ADH increases the permeability of DCT
and CT?
- ADH binds to V2 receptors, which are Gprotein receptors which activate cAMP,
second messenger in DCT and CT
- It increases the permeability to water by
insertion of Aquaporins (AQP-2 water
channels in the luminal membrane)
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Mechanism
of action
of ADH
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 We
will study vasarecta, which works as
counter current exchanger and preserves the
medullary osmotic gradient, created by LH
 Vasarecta are freely permeable to NaCl and
H2O. As blood passes down the descending
limb of vasarecta, it picks up salt and loses
H2O, till it is hypertonic at the bottom(1200
mOsm ).
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 As
blood flows up in the ascending limb of
vasarecta, salt moves into the interstium and
water enters the vasarecta, therefore,
concentration falls in the ascending limb of
vasarecta ( 300-350 mOsm ).
 This passive exchange of NaCl and H2O in the
descending and ascending limbs of vasarecta
and interstial fluid is known as counter
current exchange
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VASARECTA – COUNTER CURRENT EXCHANGE IN THE RENAL
MEDULLA
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• The vasa recta
serve as
countercurrent
exchangers
• Vasa recta blood
flow is low
(only 1-2 % of
total renal
blood flow)
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 Loop
of Henle – counter current multiplier
establishes the concentration gradient in the
medullary interstitial fluid.
 Vasarecta – counter current exchanger
maintains the concentration gradient in the
medullary interstitial fluid.
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 Urea
contributes to hyper osmotic renal
medullary interstial fluid and to
concentrated urine. How ?
- Urea is absorbed in PCT – 50%
- 50% urea comes to DCT and CT, they are not
permeable to urea but collecting duct in the
inner medulla is permeable
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- When water is reabsorbed in DCT and CT
under action of ADH, urea is more
concentrated
- Urea diffuses from CT in the inner medullary
region and contributes to the concentration
of medullary interstial fluid
- Increased urea present in the interstial fluid
diffuses into loop of Henle (descending and
ascending limbs) and then to DCT and CT,
therefore, recirculates many times before it
is excreted – called Urea Cycle
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Recirculation of Urea Absorbed from Medullary
Collecting Duct into Interstitial Fluid
Figure 28-5; Guyton and Hall
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 Micturition
or Urination is the process by
which bladder is emptied, and is governed by
two mechanism:
1. Micturition Reflex
2. Voluntary Control
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1.



Micturition Reflex
It is initiated when stretch receptors in the
urinary bladder are stimulated
Bladder can accommodate 250 – 400ml of
urine
Urine urge is felt when there is 150ml of
urine in the bladder
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Normal Cystogram
There are 3 phases of vesicular
pressure changes
1.
Initial 10 cm of H2O rise in
pressure for 10-50 ml of urine
collection
2.
Second phase last until the
bladder volume is 400ml
3.
Third phase shows the sharp
rise in the intravesicle
pressure
•Micturition contractions begin to
appear at a urine volume about
150 ml.
•Desire to void urine occurs when
the bladder is full.
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When amount of urine increases, there is greater
distension – afferent impulses from stretch
receptors go to spinal cord via pelvic nerves.
 Center in the spinal cord is S2,3,4
 Efferent impulses pass via parasympathetic
nerves to the bladder
 Parasympathetic supply causes bladder smooth
muscle to contract and urine is expelled through
urethra by force of bladder smooth muscle
contraction

IMPORTANT – Micturition reflex is spinal reflex
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Urinary Bladder and Its Innervation
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Voluntary Control of Micturition
Micturition is spinal reflex , but facilitated and
inhibited by higher Brain centers.
- Voluntary Control is done by tightening the
external uretheral sphincter and pelvic
diaphragm , through pudendal nerve by
impulses coming from brain, pons and
cerebral cortex to the spinal cord
1.
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Reflex and
Voluntary
Control of
Micturition
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Urinary Incontinence
 Urinary Incontinence is loss of voluntary
control over urination, therefore, inability to
prevent discharge of urine
 Cause – spinal cord injury to S2,3,4
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 Renal
Failure causes kidney functions to be
affected
 Causes of Renal Failure
1. Infections – urinary tract infection
2. Toxic agents e.g. lead, arsenic, pesticides
3. Drugs – aspirin
4. Immune response glomerulonephritis,
following post streptococcal throat infection
5. Kidney stone, tumor, enlarged prostate
gland
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 Renal
failure maybe
- Acute Renal Failure
- Chronic Renal Failure
1.
2.
Acute Renal Failure – sudden with
decreased urinary output, less than 500ml
per day
Chronic Renal Failure – slow progressive loss
of renal function. It is not reversible
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 Only
25% of kidney tissue is needed to
adequately maintain all the functions of
kidney
 When 75% of kidney tissue is destroyed then
loss of kidney function is noticeable
 End stage renal failure – when 90% of kidney
function is lost
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Chronic renal failure can cause
- Uremia (increased blood urea level)
- Metabolic acidosis
- Hyperkalemia
- Na+ imbalance
- Hypertension
- Edema (loss of plasma protein)
- Anemia (decreased erythropoietin)


Treatment for CRF
- Dialysis
- Kidney transplantation
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Describe the factors that determine the ability
of loop of Henle to create osmotic medullary
gradient
 Identify countercurrent multiplier and
countercurrent exchange systems in
concentrating and diluting urine
 Explain changes in osmolarity of tubular fluid in
the various segments of the loop of Henle when
concentrated urine is being produced.
 Describe the role of ADH on the ability of the
kidney to produce either a dilute or a
concentrated urine.
 Micturition reflex.

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