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DR. URVASHI SODVADIYA
 Introduction
 Normal anatomy of kidney
 Nephron
 Juxtaglomerular apparatus
 Clearance
 tubular function
 Regulation of water and ion reabsorption
 Types of water reabsorption
 Mechanism of urine concentration and dilution
 Counter current mechanism
--Other excretory organs are:
Skin
Lungs
GI tract : i. Heavy metals
ii. Drugs
iii. Fatty substances
CONTAINS 2 kidneys, 2 ureter, 1 bladder, 1 urethra.
Location
Function
Excretion
Water &
electrolyte
balance
Regulation
of calcitriol
Erythrocyte
production
Acid base
balance
Arterial
pressure
Glucose
synthesis
PARTS OF KIDNEY :
• Renal cortex
• Renal medulla
• Renal pyramid
• Major calyx
• Minor calyx
• Pelvis
• Ureter
• Renal artery & vein
Number of nephron : 1 million
Conditions when number of
nephron decreases
Parts :
a. Bowman’s capsule
b. Proximal tubule
c. Loop of henle
d. Distal tubule
e. Collecting duct
a
b
d
e c
 2 TYPES :
I. Cortical nephron
II.Juxtamedullary nephron
 JUXTAGLOMERULAR
APPARATUS
- Macula densa
JUXTAGLOMERULAR APPARATUS
Cx =
Ux . V
Px
Urine concentration (mg/mL)c
Urine flow rate (mL/min)
Plasma concentration (mg/mL)
After glomerular filtration ; tubular handling of filtrate
is most important step
Glomerular filtration : NONSPECIFIC process
Tubular transport : SELECTIVE process
Control of ECF & urine volume and composition
PASSIVE
diffusion
Facilitated
diffusion
Solvent
drag
osmosis
ACTIVE
Secondary
active
transport
PARA
TRANS
PARA
TRANS
Tubular load : total amount of solute filtered by all the
nephrons of both kidneys per minute.
Tubular load for glucose = 125 mg/min
Transport maximum (Tm) : maximum amount of solute
that can be reabsorbed by all nephrons of both kidneys
per minute .
Tm for glucose (in normal condition ) = 320 mg/min in
females ,375 mg/min in males
average = 360 mg/min
Glucose lost in urine = tubular load of glucose – Tm for glucose
Difference between theoretical and practical values (eg.
for glucose)
o Theoretically : tubular load : 350 mg/min --- not
excreted in urine
o Practically : tubular load : 225 mg/min --- excreted
in urine
Reasons: 1.heterogenecity of nephrons
2. kinetic of transport
Phenomenon : “SPLAY”
RENAL THRESHOLD :
“Concentration of solute in the plasma at or above which the
solute first appears in urine”
Eg : renal threshold of glucose :
--180mg% in venous plasma
--200 mg% in arterial plasma
Most important part of nephron
It reabsorbs about 67% of filtered water,Na+ ,Cl- ,K+
and HCO3- and almost all filtered glucose and amino
acid
PCT
Convoluted
Straight
Functionally both parts are
similar with few minor
differences
Important among all transport
processes
Entry of Na+
into tubular
cells
Cotransport
Antiport
mechanism
Associated
anion
reabsorption
Glucose,amino
acids,phosphates
etc
“SECONDARY
ACTIVE
TRANSPORT”
Na+ - H+
exchanger
“Accounts for
60% of total
Na+ entry”
HCO3- & Cl-
Process of
absorption is
different
2 REASONS :
 Presence of more anion-antiporter
in distal part of proximal tubule
 Concentration of Cl- is very high in
this part
Transfer of large amount of
water helps in transfer of
ions like K+ and Ca++ that
are carried along with water
“ SOLVENT DRAG”
 Totally reabsorb in PCT
 By 2 mechanism: i. “secondary active transport”
ii. Degraded by cellular enzymes in epithelial
swretetrytytiujtregfhgjcells of PCT
 Urine is practically protein free!
 Cl- : mainly reabsorbed along with Na+ reabsorption
 Recently , separate chloride channels have been identified in
kidney tubules
 These Cl- channels are linked with Ca++ channels
Proximal tubules secretes various organic cations and
anions ; eg. Uric acid,PAH,drugs etc.
Plasma protein bound substance : not filtered in
glomerular filtration
Physiological significance : eg of gout
JUXTAMEDULLARY nephrons:
 Longer
 less in num
 LOH of this type;helps in
‘urine concentration
 LOH reabsorbes : 25% of filtered NaCl and K+
30% of filtered Ca++
65% of filtered Mg++
 Descending limb of LOH: “Permeable” to water
 Ascending limb of LOH: “Impermeable” to water
CORTICAL nephrons:
 Shorter
 More in num
LOH of this type;helps in ‘urine
formation’
2 STEPS
Transport of Solutes &
Reabsorption of water
 Physiologically it is close to thick
ascending LOH ; therefore it is
“RELATIVELY IMPERMEABLE TO
WATER”
 Only 5% of filtered water is removed in
DCT
Strictly speaking; it is not a part of an individual nephron but
is considered as distal part of nephrons
Important mechanisms: K+ excretion and hormonal water
reabsorption
DCT
Principal
cells
Intercalated
cells
Reabsorbe Na+ & secrete K+
Secrete either H+ or HCO3-
K+ metabolism
Acidification of urine
FUNCTION OF
PRINCIPAL CELLS
FUNCTION OF
INTERCALATED CELLS
IN CORTICAL PART
DIABETES INSIPIDUS: Access urine formation; 2 types:
 Neurogenic DI -- due to ADH deficiency
 Nephrogenic DI -- failure of collecting duct to respond to hormone (due to
mutation in gene for V2 receptor
IN MEDULLARY PART
 Presence of adequate ADH:
1400 mosm/kg of H2O
(97.7% of filtered water is absorbed)
 Absence of ADH:
30 mosm/kg of H2O
 Relatively impermeable; even in
absence of ADH : about 2% filtered
water is reabsorbed
Osmolality of interstitium is very high
Accounts for about 5% of water
reabsorption
Hormonal factors
Neural factors
Starling forces
Tubuloglomerular feedback
Glomerulartubulo balance
Through sympathetic innervation of kidney
Activation leads to increase reabsorption of
water & NaCl
Find the site to
mention it
Dopamine
GlucocorticoidsUrodilatin
ANP
ADH
Aldosterone
Angiotensin II
Acts on PCT
NaCl &water
reabsorption
Acts on PCT
NaCl &water
reabsorption
-Have mild
mineralocorticoid
activity
-Acts on PCT
- NaCl &water
reabsorption
-secreted by DCT &
CD
-Acts on collecting
duct
- NaCl &water
reabsorption
-secreted by
myocytes of atria of
heart
-Acts on collecting
duct & DCT
- NaCl &water
reabsorption
2 TYPES
Obligatory reabsorption
Facultative reabsorption
 Secondary to reabsorption
of solutes
 85%
 PCT
 Secondary to effect of
hormones
 15%
 DCT & collecting duct
GFR : 180 L/day, 1.5 L of urine is excreted daily
Kidney excretes concentrated urine to prevent volume
depletion from the body, in which osmolality of urine is
an index of its concentrating and diluting capacity
Under physiological condition , urine osmolality is a
function of solvent (water) excretion
Example of desert
ADH: external factor for kidney plays an important role
in urine concentration and dilution
Counter current means
“flow of fluid in opposite
direction in adjacent
structure”
Requires 3 conditions :
a. two tubes, should run
parallel to each other
b. movement of fluid
c. should be close proximity
to each other and should be
selectively permeable
KIDNEY
Counter current
multiplication
system
Counter current
exchange system
LOOP OF HENLE
VASA RECTA
Osmotic
equilibrating device
COLLECTING
DUCT
Small osmotic gradient established -
 multiplied into larger gradient :
“SINGLE EFFECT”
As tubular fluid in loop enters deeper
layer of medulla; becomes more
concentrated based on increasing
gradient of osmolality along axis of
loop  “AXIAL GRADIENT”
 3 MAIN FACTORS :
A. The rate of fluid flow
B. Strength of single effect
C. The length of LOH
 The tubular fluid and blood in vasa recta entering into medulla becomes
gradually hyperosmolal and fluid and blood leaving medulla becomes
gradually hyposmolal. Thus interstitial osmolality increases gradually from
outer layers to inner layers of medulla reaching about 1200 mosm/kg of
water in innermost part. This osmolal gradient transfers water from tubular
fluid of collecting duct leaving the medulla that makes urine concentrated.
Urine formation

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Urine formation

  • 2.  Introduction  Normal anatomy of kidney  Nephron  Juxtaglomerular apparatus  Clearance  tubular function  Regulation of water and ion reabsorption  Types of water reabsorption  Mechanism of urine concentration and dilution  Counter current mechanism
  • 3. --Other excretory organs are: Skin Lungs GI tract : i. Heavy metals ii. Drugs iii. Fatty substances
  • 4. CONTAINS 2 kidneys, 2 ureter, 1 bladder, 1 urethra.
  • 6. PARTS OF KIDNEY : • Renal cortex • Renal medulla • Renal pyramid • Major calyx • Minor calyx • Pelvis • Ureter • Renal artery & vein
  • 7. Number of nephron : 1 million Conditions when number of nephron decreases Parts : a. Bowman’s capsule b. Proximal tubule c. Loop of henle d. Distal tubule e. Collecting duct a b d e c
  • 8.  2 TYPES : I. Cortical nephron II.Juxtamedullary nephron  JUXTAGLOMERULAR APPARATUS - Macula densa
  • 10. Cx = Ux . V Px Urine concentration (mg/mL)c Urine flow rate (mL/min) Plasma concentration (mg/mL)
  • 11.
  • 12.
  • 13. After glomerular filtration ; tubular handling of filtrate is most important step Glomerular filtration : NONSPECIFIC process Tubular transport : SELECTIVE process Control of ECF & urine volume and composition
  • 16. Tubular load : total amount of solute filtered by all the nephrons of both kidneys per minute. Tubular load for glucose = 125 mg/min Transport maximum (Tm) : maximum amount of solute that can be reabsorbed by all nephrons of both kidneys per minute . Tm for glucose (in normal condition ) = 320 mg/min in females ,375 mg/min in males average = 360 mg/min Glucose lost in urine = tubular load of glucose – Tm for glucose
  • 17. Difference between theoretical and practical values (eg. for glucose) o Theoretically : tubular load : 350 mg/min --- not excreted in urine o Practically : tubular load : 225 mg/min --- excreted in urine Reasons: 1.heterogenecity of nephrons 2. kinetic of transport Phenomenon : “SPLAY”
  • 18. RENAL THRESHOLD : “Concentration of solute in the plasma at or above which the solute first appears in urine” Eg : renal threshold of glucose : --180mg% in venous plasma --200 mg% in arterial plasma
  • 19. Most important part of nephron It reabsorbs about 67% of filtered water,Na+ ,Cl- ,K+ and HCO3- and almost all filtered glucose and amino acid PCT Convoluted Straight Functionally both parts are similar with few minor differences
  • 20. Important among all transport processes
  • 21. Entry of Na+ into tubular cells Cotransport Antiport mechanism Associated anion reabsorption Glucose,amino acids,phosphates etc “SECONDARY ACTIVE TRANSPORT” Na+ - H+ exchanger “Accounts for 60% of total Na+ entry” HCO3- & Cl- Process of absorption is different 2 REASONS :  Presence of more anion-antiporter in distal part of proximal tubule  Concentration of Cl- is very high in this part
  • 22. Transfer of large amount of water helps in transfer of ions like K+ and Ca++ that are carried along with water “ SOLVENT DRAG”
  • 23.
  • 24.  Totally reabsorb in PCT  By 2 mechanism: i. “secondary active transport” ii. Degraded by cellular enzymes in epithelial swretetrytytiujtregfhgjcells of PCT  Urine is practically protein free!  Cl- : mainly reabsorbed along with Na+ reabsorption  Recently , separate chloride channels have been identified in kidney tubules  These Cl- channels are linked with Ca++ channels
  • 25. Proximal tubules secretes various organic cations and anions ; eg. Uric acid,PAH,drugs etc. Plasma protein bound substance : not filtered in glomerular filtration Physiological significance : eg of gout
  • 26. JUXTAMEDULLARY nephrons:  Longer  less in num  LOH of this type;helps in ‘urine concentration  LOH reabsorbes : 25% of filtered NaCl and K+ 30% of filtered Ca++ 65% of filtered Mg++  Descending limb of LOH: “Permeable” to water  Ascending limb of LOH: “Impermeable” to water CORTICAL nephrons:  Shorter  More in num LOH of this type;helps in ‘urine formation’
  • 27. 2 STEPS Transport of Solutes & Reabsorption of water
  • 28.
  • 29.  Physiologically it is close to thick ascending LOH ; therefore it is “RELATIVELY IMPERMEABLE TO WATER”  Only 5% of filtered water is removed in DCT
  • 30. Strictly speaking; it is not a part of an individual nephron but is considered as distal part of nephrons Important mechanisms: K+ excretion and hormonal water reabsorption DCT Principal cells Intercalated cells Reabsorbe Na+ & secrete K+ Secrete either H+ or HCO3- K+ metabolism Acidification of urine
  • 31. FUNCTION OF PRINCIPAL CELLS FUNCTION OF INTERCALATED CELLS
  • 33. DIABETES INSIPIDUS: Access urine formation; 2 types:  Neurogenic DI -- due to ADH deficiency  Nephrogenic DI -- failure of collecting duct to respond to hormone (due to mutation in gene for V2 receptor IN MEDULLARY PART  Presence of adequate ADH: 1400 mosm/kg of H2O (97.7% of filtered water is absorbed)  Absence of ADH: 30 mosm/kg of H2O  Relatively impermeable; even in absence of ADH : about 2% filtered water is reabsorbed Osmolality of interstitium is very high Accounts for about 5% of water reabsorption
  • 34. Hormonal factors Neural factors Starling forces Tubuloglomerular feedback Glomerulartubulo balance Through sympathetic innervation of kidney Activation leads to increase reabsorption of water & NaCl Find the site to mention it
  • 35. Dopamine GlucocorticoidsUrodilatin ANP ADH Aldosterone Angiotensin II Acts on PCT NaCl &water reabsorption Acts on PCT NaCl &water reabsorption -Have mild mineralocorticoid activity -Acts on PCT - NaCl &water reabsorption -secreted by DCT & CD -Acts on collecting duct - NaCl &water reabsorption -secreted by myocytes of atria of heart -Acts on collecting duct & DCT - NaCl &water reabsorption
  • 36. 2 TYPES Obligatory reabsorption Facultative reabsorption  Secondary to reabsorption of solutes  85%  PCT  Secondary to effect of hormones  15%  DCT & collecting duct
  • 37. GFR : 180 L/day, 1.5 L of urine is excreted daily Kidney excretes concentrated urine to prevent volume depletion from the body, in which osmolality of urine is an index of its concentrating and diluting capacity Under physiological condition , urine osmolality is a function of solvent (water) excretion Example of desert ADH: external factor for kidney plays an important role in urine concentration and dilution
  • 38. Counter current means “flow of fluid in opposite direction in adjacent structure” Requires 3 conditions : a. two tubes, should run parallel to each other b. movement of fluid c. should be close proximity to each other and should be selectively permeable
  • 39. KIDNEY Counter current multiplication system Counter current exchange system LOOP OF HENLE VASA RECTA Osmotic equilibrating device COLLECTING DUCT
  • 40. Small osmotic gradient established -  multiplied into larger gradient : “SINGLE EFFECT” As tubular fluid in loop enters deeper layer of medulla; becomes more concentrated based on increasing gradient of osmolality along axis of loop  “AXIAL GRADIENT”  3 MAIN FACTORS : A. The rate of fluid flow B. Strength of single effect C. The length of LOH
  • 41.  The tubular fluid and blood in vasa recta entering into medulla becomes gradually hyperosmolal and fluid and blood leaving medulla becomes gradually hyposmolal. Thus interstitial osmolality increases gradually from outer layers to inner layers of medulla reaching about 1200 mosm/kg of water in innermost part. This osmolal gradient transfers water from tubular fluid of collecting duct leaving the medulla that makes urine concentrated.